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Zhao CF, Lan L, Shi XY, Li J, Fan S. Assessment the real-world safety of intravitreal dexamethasone implant (Ozurdex): novel insights from a comprehensive pharmacovigilance analysis utilizing the FAERS database. BMC Pharmacol Toxicol 2025; 26:29. [PMID: 39930531 PMCID: PMC11809023 DOI: 10.1186/s40360-025-00866-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/04/2025] [Indexed: 02/13/2025] Open
Abstract
OBJECTIVE The intravitreal dexamethasone implant (Dex) is widely used for various ocular conditions, including diabetic macular edema (DME), retinal vein occlusion (RVO), and non-infectious uveitis. Despite its efficacy, concerns remain regarding its safety profile. This study aims to analyze the adverse events (AEs) associated with Dex reported in the FDA Adverse Event Reporting System (FAERS) database from 2010 to 2024. METHODS Data were extracted from FAERS, focusing on cases where Dex was the primary suspect drug. The dataset was processed to eliminate duplicates and incomplete entries. Disproportionality analysis, including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR), was used to detect safety signals. AEs were categorized by system organ class (SOC) and preferred term (PT). RESULTS A total of 1,588 adverse event reports (AERs) were analyzed, revealing a significant upward trend. The Eye disorders was the most commonly reported SOC, with strong disproportionality signals (ROR: 45.11; PRR: 23.71). Key AEs identified at the PT level included Corneal decompensation, Choroidal hematoma, and Posterior capsule rupture, which were not listed on the drug label. Considering the reported numbers, the Endophthalmitis was the most common AE. Additionally, a significant proportion of AEs were observed within the first seven days post-administration, emphasizing the need for monitoring. CONCLUSION While Dex remains an effective treatment option for ocular conditions, its use is associated with significant risks, particularly regarding unexpected and severe complications such as corneal decompensation. Continuous pharmacovigilance and detailed patient monitoring are essential to mitigate these risks. Future studies should focus on prospective designs and comprehensive clinical data to better understand the safety profile of Dex.
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Affiliation(s)
- Chao-Fu Zhao
- Department of Ophthalmology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China
| | - Lina Lan
- Department of Ophthalmology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China
| | - Xing-Yu Shi
- Department of Nephrology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China
| | - Jun Li
- Department of Ophthalmology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.
| | - Shipei Fan
- Department of Ophthalmology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.
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Doganay S, Ucan Gunduz G, Kiristioglu MO, Demirel E, Yalcinbayir O. Safety and efficacy of supraciliary dexamethasone implantation for macular oedema: a preliminary comparative study. Eye (Lond) 2025; 39:586-592. [PMID: 39774295 PMCID: PMC11794867 DOI: 10.1038/s41433-024-03570-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 11/26/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
PURPOSE To evaluate the efficacy and safety of dexamethasone implantation in the supraciliary (SC) space, a novel and potential effective implantation site, compared to intravitreal (IV) application. METHODS This prospective study included 39 eyes of 38 patients with macular oedema (ME) who underwent SC and IV dexamethasone implantation (SC-DEX and IV-DEX). Patients were randomly assigned to treatment groups and followed for 3 months. Preoperative and postoperative assessments included maximum retinal thickness (MRT), change in central retinal thickness between consecutive visits (ΔCRT), intraocular pressure (IOP), and best corrected visual acuity (BCVA). RESULTS Both SC-DEX and IV-DEX groups showed significant MRT reductions during at follow-up. In the SC group, MRT significantly decreased at 1st and 3rd months (p = 0.0002 for both), but not at 1st week (p = 0.2517). In the IV-DEX group, significant reductions in MRT were observed at all postoperative visits: 1st week (p = 0.0002), 1st month (p = 0.0004), and 3rd month (p = 0.0003). There were no significant differences in the change in ΔCRT between the SC-DEX and IV-DEX groups at any visit (p > 0.05). IOP did not show significant changes (p > 0.05). BCVA improved significantly in the SC group compared to the IV-DEX group during the first week (p = 0.014). No other perioperative or postoperative sight-threatening complications were noted in either group, including hypotony or endophthalmitis. CONCLUSION SC-DEX shows promise as an alternative for managing ME, offering similar effectiveness to IV-DEX with safe profile. Further studies are needed to confirm its long-term safety and efficacy.
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Affiliation(s)
- Selim Doganay
- Department of Ophthalmology, Bursa Uludag University School of Medicine, Bursa, Turkey.
| | - Gamze Ucan Gunduz
- Department of Ophthalmology, Bursa Uludag University School of Medicine, Bursa, Turkey.
| | | | - Elif Demirel
- Department of Ophthalmology, Bursa Uludag University School of Medicine, Bursa, Turkey
| | - Ozgur Yalcinbayir
- Department of Ophthalmology, Bursa Uludag University School of Medicine, Bursa, Turkey
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Nauman A, Iqbal K, Seyal M. Effect of Suprachoroidal Triamcinolone Acetonide on Intraocular Pressure in Macular Edema: A Retrospective Study. Cureus 2025; 17:e77282. [PMID: 39931603 PMCID: PMC11809668 DOI: 10.7759/cureus.77282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2025] [Indexed: 02/13/2025] Open
Abstract
Introduction Macular edema causes decreased vision in diseases like diabetic retinopathy, uveitis, retinal vein occlusions and post-cataract surgery cystoid macular edema. Steroids in the depot form of triamcinolone acetonide (TA) increase the duration of action, but due to a number of complications, especially raising intraocular pressure (IOP), anti-vascular endothelial growth factor (anti-VEGF) injections are now considered the mainstay of treatment. The suprachoroidal space provides an alternate route for steroid delivery, limiting the drug to the posterior segment, hence preventing the adverse effects on the anterior segment. This study aimed to determine the safety of suprachoroidal steroids with respect to their effect on IOP. Methods This retrospective study involved patients who received suprachoroidal TA injections for macular edema: diabetic retinopathy, retinal vein occlusions, uveitis and cystoid macular edema post-cataract surgery at Layton Rahmatulla Benevolent Trust (LRBT) Free Eye Hospital, Lahore, Pakistan. Manual medical records from two years were accessed and all patients were included in the study. Patients with a history of ocular hypertension, glaucoma and steroid responsiveness had not received the injection. Crystalline steroid particles of 4 mg/0.1 mL, using an intravenous TA (K-Kort; GlaxoSmithKline, Brentford, UK), were injected into the suprachoroidal space through a 30-gauge syringe with a custom plastic sleeve from a 24-gauge branula exposing 0.1 mm of the bevel. IOP was recorded at baseline before the injection and at weeks 2, 4 and 8. Repeated measures multivariate analysis of variance (ANOVA) was used to compare IOP measurements at the different time intervals. Results A total of 61 patients were included, with 70 eyes being assessed, at a mean age of 54.2 ± 10.4 years. Baseline mean IOP was 16.41 ± 2.62 mmHg, 17.04 ± 3.09 mmHg at week 2, 16.30 ± 2.95 mmHg at week 4 and 15.73 ± 1.83 mmHg at week 8. Between baseline IOP and week 2, the mean difference was 1.11 ± 0.66 mmHg (p = 0.59), 0.26 ± 0.43 mmHg from week 2 to week 4 (p = 1.00), and 1.36 ± 0.51 mmHg from week 4 to week 8 (p = 0.51). The mean IOP decreased by 0.50 ± 0.53 mmHg (p = 1.00) from baseline by eight weeks. The differences between IOP, different causes of macular edema and age or gender were not statistically significant. Two patients (1.4%) had a temporary rise in IOP above 24 mmHg requiring ocular medication, with one having a rise above 30 mmHg. Conclusion A single injection of suprachoroidal TA temporarily raises the mean IOP, but the increase is insignificant and settles to baseline by two months. Further studies would be required to establish suprachoroidal triamcinolone as a cost-effective and safe treatment for macular edema.
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Affiliation(s)
- Ali Nauman
- Ophthalmology, LRBT (Layton Rahmatulla Benevolent Trust) Free Eye Hospital, Lahore, PAK
| | - Kashif Iqbal
- Vitreoretinal Ophthalmology, LRBT (Layton Rahmatulla Benevolent Trust) Free Eye Hospital, Lahore, PAK
| | - Mishal Seyal
- Ophthalmology, LRBT (Layton Rahmatulla Benevolent Trust) Free Eye Hospital, Lahore, PAK
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Arora A, Morya AK, Gupta PC, Menia NK, Nishant P, Gupta V. Intravitreal therapy for the management of diabetic retinopathy: A concise review. World J Exp Med 2024; 14:99235. [PMID: 39713073 PMCID: PMC11551706 DOI: 10.5493/wjem.v14.i4.99235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 09/08/2024] [Accepted: 09/20/2024] [Indexed: 10/31/2024] Open
Abstract
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus and may result in irreversible visual loss. Laser treatment has been the gold standard treatment for diabetic macular edema and proliferative diabetic retinopathy for many years. Of late, intravitreal therapy has emerged as a cornerstone in the management of DR. Among the diverse pharmacotherapeutic options, anti-vascular endothelial growth factor agents have demonstrated remarkable efficacy by attenuating neovascularization and reducing macular edema, thus preserving visual acuity in DR patients.
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Affiliation(s)
- Atul Arora
- Teleophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, Punjab, India
| | - Arvind K Morya
- Department of Ophthalmology, All India Institute of Medical Sciences, Hyderabad 508126, Telangana, India
| | - Parul C Gupta
- Department of Ophthalmology, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, Punjab, India
| | - Nitin K Menia
- Department of Ophthalmology, All India Institute of Medical Sciences, Vijaypur 180001, Jammu and Kashmīr, India
| | - Prateek Nishant
- Department of Ophthalmology, ESIC Medical College, Patna 801103, Bihār, India
| | - Vishali Gupta
- Department of Ophthalmology, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, Punjab, India
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Kim M, Jung MY, Lee DY, Ahn SM, Lee GM, Park CY. How to Fabricate Hyaluronic Acid for Ocular Drug Delivery. Pharmaceutics 2024; 16:1604. [PMID: 39771582 PMCID: PMC11680071 DOI: 10.3390/pharmaceutics16121604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/13/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
This review aims to examine existing research on the development of ocular drug delivery devices utilizing hyaluronic acid (HA). Renowned for its exceptional biocompatibility, viscoelastic properties, and ability to enhance drug bioavailability, HA is a naturally occurring biopolymer. The review discussed specific mechanisms by which HA enhances drug delivery, including prolonging drug residence time on ocular surfaces, facilitating controlled drug release, and improving drug penetration through ocular tissues. By focusing on these unique functionalities, this review highlights the potential of HA-based systems to revolutionize ocular treatment. Various fabrication techniques for HA-based ocular drug delivery systems, including hydrogels, nanoparticles, and microneedles, are discussed, highlighting their respective advantages and limitations. Additionally, this review explores the clinical applications of HA-based devices in treating a range of ocular diseases, such as dry eye syndrome, glaucoma, retinal disorders, and ocular infections. By comparing the efficacy and safety profiles of these devices with traditional ocular drug delivery methods, this review aims to provide a comprehensive understanding of the potential benefits and challenges associated with HA-based systems. Moreover, this review discusses current limitations and future directions in the field, such as the need for standardized fabrication protocols, long-term biocompatibility studies, and large-scale clinical trials. The insights and advancements presented in this review aim to guide future research and development efforts, ultimately enhancing the effectiveness of ocular drug delivery and improving patient outcomes.
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Affiliation(s)
- Martha Kim
- Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (M.K.); (M.-Y.J.); (D.-Y.L.); (S.M.A.); (G.M.L.)
| | - Mi-Young Jung
- Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (M.K.); (M.-Y.J.); (D.-Y.L.); (S.M.A.); (G.M.L.)
| | - Do-Yeon Lee
- Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (M.K.); (M.-Y.J.); (D.-Y.L.); (S.M.A.); (G.M.L.)
| | - So Min Ahn
- Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (M.K.); (M.-Y.J.); (D.-Y.L.); (S.M.A.); (G.M.L.)
| | - Gyeong Min Lee
- Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (M.K.); (M.-Y.J.); (D.-Y.L.); (S.M.A.); (G.M.L.)
| | - Choul Yong Park
- Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
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Boscia F, Veritti D, Iaculli C, Lattanzio R, Freda S, Piergentili B, Varano M. Management of treatment-naïve diabetic macular edema patients: Review of real-world clinical data. Eur J Ophthalmol 2024; 34:1675-1694. [PMID: 38462923 DOI: 10.1177/11206721241237069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME.
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Affiliation(s)
- Francesco Boscia
- Department of Translational Medicine and Neurosciences (DiBraiN), University of Bari, Bari, Italy
| | - Daniele Veritti
- Department of Medicine - Ophthalmology, University of Udine, Udine, Italy
| | - Cristiana Iaculli
- Department of Ophthalmology, Policlinico Riuniti Di Foggia, University of Foggia, 71122, Foggia, Italy
| | - Rosangela Lattanzio
- Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Simona Freda
- AbbVie S.r.l., SR 148 Pontina, 04011, Campoverde, LT
| | | | - Monica Varano
- Ophthalmology Department, IRCCS - Fondazione Bietti, Rome, Italy
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Torkashvand A, Izadian A, Hajrasouliha A. Advances in ophthalmic therapeutic delivery: A comprehensive overview of present and future directions. Surv Ophthalmol 2024; 69:967-983. [PMID: 38986847 PMCID: PMC11392635 DOI: 10.1016/j.survophthal.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 07/12/2024]
Abstract
Ophthalmic treatment demands precision and consistency in delivering therapeutic agents over extended periods to address many conditions, from common eye disorders to complex diseases. This diversity necessitates a range of delivery strategies, each tailored to specific needs. We delve into various delivery cargos that are pivotal in ophthalmic care. These cargos encompass biodegradable implants that gradually release medication, nonbiodegradable implants for sustained drug delivery, refillable tools allowing flexibility in treatment, hydrogels capable of retaining substances while maintaining ocular comfort, and advanced nanotechnology devices that precisely target eye tissues. Within each cargo category, we explore cutting-edge research-level approaches and FDA-approved methods, providing a thorough overview of the current state of ophthalmic drug delivery. In particular, our focus on nanotechnology reveals the promising potential for gene delivery, cell therapy administration, and the implantation of active devices directly into the retina. These advancements hold the key to more effective, personalized, and minimally- invasive ophthalmic treatments, revolutionizing the field of eye care.
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Affiliation(s)
- Ali Torkashvand
- Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Afshin Izadian
- Electrical and Computer Engineering Technology, Purdue University, West Lafayette, IN, United States
| | - Amir Hajrasouliha
- Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States.
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Borella Y, Bertaud S, Tadayoni R, Bodaghi B, Dupas B, Touhami S. Switching to subtenon triamcinolone acetonide does not jeopardize the functional and anatomic outcomes of dexamethasone implant treated eyes with diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2024; 262:3135-3142. [PMID: 38668853 DOI: 10.1007/s00417-024-06492-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 03/18/2024] [Accepted: 04/12/2024] [Indexed: 10/08/2024] Open
Abstract
BACKGROUND Intraocular dexamethasone implant (DEXi) is an efficient treatment for diabetic macular edema (DME). However, it may be unavailable or contraindicated. Triamcinolone acetonide is another corticosteroid that has proved to be safe and effective in treating macular edema complicating various diseases including diabetes. The purpose of this study is to evaluate the outcomes of a switch from DEXi to subtenon triamcinolone acetonide (STTA) and back, in eyes with DME. METHODS Retrospective study. DME eyes that had been treated with DEXi and switched to STTA between October 2018 and February 2019 (stock shortage of DEXi) were included. The functional and anatomical outcomes of the switch and switch-back were studied. RESULTS 26 eyes of 17 patients (mean age 67.1 ± 8.2 years) were considered. The mean baseline visual acuity (VA) was 0.35 ± 0.17 decimals remaining stable after DEXi, STTA and switch-back to DEXi. The mean central macular thickness (CMT) was 492.7 ± 32.8 µm initially, decreasing to 294.3 ± 133.4 µm after DEXi, 369.9 ± 182.3 µm after STTA and 297.6 ± 72.0 µm after switching back to DEXi (all p < 0.05 versus baseline). Compared to baseline, the CMT reduction was numerically better after DEXi and switching back to DEXi than after STTA (mean reduction: -200.4 µm, -167.7 µm, and -95.08 µm respectively, p = 0.13). Intraocular pressure was comparable after DEXi and STTA. CONCLUSION DEXi is the steroid of choice in DME. However, STTA can be a cost-effective alternative when DEXi is unavailable or contraindicated. This study suggests that STTA may be used in the context of a step therapy in DME.
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Affiliation(s)
- Ysé Borella
- Department of Ophthalmology, Sorbonne Université, Pitié-Salpêtrière University Hospital, 75013, Paris, France
| | - Samuel Bertaud
- Ophthalmology Department, Université de Paris, APHP, Hôpital Lariboisière, 75010, Paris, France
| | - Ramin Tadayoni
- Ophthalmology Department, Université de Paris, APHP, Hôpital Lariboisière, 75010, Paris, France
| | - Bahram Bodaghi
- Department of Ophthalmology, Sorbonne Université, Pitié-Salpêtrière University Hospital, 75013, Paris, France
| | - Bénédicte Dupas
- Ophthalmology Department, Université de Paris, APHP, Hôpital Lariboisière, 75010, Paris, France
| | - Sara Touhami
- Department of Ophthalmology, Sorbonne Université, Pitié-Salpêtrière University Hospital, 75013, Paris, France.
- Ophthalmology Department, Université de Paris, APHP, Hôpital Lariboisière, 75010, Paris, France.
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Ruiz-Moreno JM, Gámez Lechuga M, Calvo P, Merino M, Martín Lorenzo T, Maravilla-Herrera P, Gil Jiménez B, Abraldes MJ. Burden of Disease Study of Patients with Diabetic Macular Oedema in Spain. Ophthalmol Ther 2024; 13:1937-1953. [PMID: 38771462 PMCID: PMC11178718 DOI: 10.1007/s40123-024-00959-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 04/25/2024] [Indexed: 05/22/2024] Open
Abstract
INTRODUCTION Diabetic macular oedema (DMO) is a complication of diabetic retinopathy that can result in vision loss. The disease can impact different spheres of a patient's life, including physical and psychological health, work, and activities of daily living, entailing an important use of healthcare and non-healthcare resources. This study aimed to estimate the socio-economic burden of DMO in Spain. METHODS The burden of DMO was estimated from a societal perspective, per patient, year of treatment since diagnosis, and type of treatment. Four categories were considered: direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labour productivity losses (LPL), and intangible costs (IC) associated with loss of quality of life. Average annual costs were calculated by multiplying the resources used per patient by their corresponding unit price (or financial proxy). For a more accurate estimation, differences in resource use between treatments (intravitreal anti-vascular endothelial growth factor injections of ranibizumab or aflibercept, and intravitreal dexamethasone implants) and year since diagnosis (first, second, and third year or beyond) were considered and presented separately. The reference year for costs was 2021. RESULTS The average annual costs of DMO in the first year of treatment after diagnosis was estimated at €18,774, €17,512, and €16,188 per patient treated with ranibizumab, aflibercept, and dexamethasone, respectively. This burden would be reduced to €15,783, €15,701, and €12,233 in the second year, and to €15,119, €15,043, and €12,790 in the third year, respectively. Diagnosis of DMO entails an additional one-off cost of €485. DHC accounted for the greatest proportion of total annual costs per patient, independent of the year, with LPL also making an important contribution to total costs. CONCLUSIONS The socio-economic impact of DMO on patients, the healthcare system, and society at large is substantial. The constant increase in its prevalence accentuates the need for planning and implementation of healthcare strategies to prevent vision loss and reduce the socio-economic burden of the disease.
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Affiliation(s)
- José M Ruiz-Moreno
- Ophtalmology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
| | | | - Pilar Calvo
- Medical Retina Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - María Merino
- Health Outcomes Research Department, Weber, Madrid, Spain.
| | | | | | | | - Maximino J Abraldes
- Medical Retina and Ocular Diabetes Unit, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain
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10
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Niegowski LJ, Cohen SY, Crincoli E, Mehanna CJ, Souied EH. Cognitive bias evaluation on the choice of treatment in common retinal disorders among retina specialists in 2023. J Fr Ophtalmol 2024; 47:104177. [PMID: 38603895 DOI: 10.1016/j.jfo.2024.104177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 10/01/2023] [Accepted: 10/22/2023] [Indexed: 04/13/2024]
Abstract
PURPOSE The study aimed to discern the intent to treat with the therapeutic agents prescribed first or second line in the following eye conditions: neovascular age-related macular Degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic maculopathy with choroidal neovascularization (MMNV). The study also aimed to distinguish the ophthalmologists' intended treatment for their patients from those that they would prescribe for themselves if they were affected by the above macular conditions. METHODS The study utilized an online survey of 243 French ophthalmologists practicing medical retina, with males accounting for 54.3% of the participants. Data was obtained using a questionnaire that focused on the ophthalmologists' experience with various agents as well as their first and second line choices for nAMD, DME, RVO, and MMNV. RESULTS The vast majority of French ophthalmologists (99%) had experience with the most widely used anti-vascular endothelial growth factors (anti-VEGFs); ranibizumab, bevacizumab, and aflibercept. Fewer than 8% reported experience with anti-VEGF drug reservoirs, biosimilars, or faricimab. The study findings also showed ranibizumab and aflibercept as the commonly prescribed first line choices for the above-mentioned ocular conditions. For the second line choice, the study showed that aflibercept and dexamethasone intravitreal implants were the most common across the four retinal conditions studied. The only difference in intent to treat for "patients" versus "yourself" was for biosimilars (0% to 0.8%, P=0.001). CONCLUSION The findings regarding the first and second line choices for the mentioned ocular disorders were found to agree with the findings of published literature currently used in practice, with a tendency to prefer ranibizumab as first line therapy for neovascular disorders and aflibercept as first line therapy for macular edema. In addition, there were no differences between choices for first and second line therapy for patients vs. ophthalmologists.
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Affiliation(s)
- L-J Niegowski
- Department of Ophthalmology, University of Paris Est-Creteil, Créteil, France
| | - S Y Cohen
- Department of Ophthalmology, University of Paris Est-Creteil, Créteil, France; Ophthalmology Center for Imaging and Laser, Paris, France
| | - E Crincoli
- Department of Ophthalmology, University of Paris Est-Creteil, Créteil, France
| | - C J Mehanna
- Department of Ophthalmology, University of Paris Est-Creteil, Créteil, France
| | - E H Souied
- Department of Ophthalmology, University of Paris Est-Creteil, Créteil, France.
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Wang M, Luan R, Liu B, Gong Y, Zhao J, Chen X, Yang Q, Liu J, Liu J, Shao Y, Li X. The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy. Diabetes Metab Syndr Obes 2024; 17:1199-1213. [PMID: 38476345 PMCID: PMC10929653 DOI: 10.2147/dmso.s445607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 02/21/2024] [Indexed: 03/14/2024] Open
Abstract
Purpose To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). Methods This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. Results The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). Conclusion Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. Clinical Trial Registration This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).
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Affiliation(s)
- Manqiao Wang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Rong Luan
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Boshi Liu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Yi Gong
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Jinzhi Zhao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Xiteng Chen
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Qianhui Yang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Jingjie Liu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Juping Liu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Yan Shao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
| | - Xiaorong Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China
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Salvetat ML, Pellegrini F, Spadea L, Salati C, Musa M, Gagliano C, Zeppieri M. The Treatment of Diabetic Retinal Edema with Intravitreal Steroids: How and When. J Clin Med 2024; 13:1327. [PMID: 38592149 PMCID: PMC10932454 DOI: 10.3390/jcm13051327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 02/13/2024] [Accepted: 02/21/2024] [Indexed: 04/10/2024] Open
Abstract
Diabetic macular edema (DME) is a common complication of diabetes mellitus and a leading cause of visual impairment worldwide. It is defined as the diabetes-related accumulation of fluid, proteins, and lipids, with retinal thickening, within the macular area. DME affects a significant proportion of individuals with diabetes, with the prevalence increasing with disease duration and severity. It is estimated that approximately 25-30% of diabetic patients will develop DME during their lifetime. Poor glycemic control, hypertension, hyperlipidemia, diabetes duration, and genetic predisposition are recognized as risk factors for the development and progression of DME. Although the exact pathophysiology is still not completely understood, it has been demonstrated that chronic hyperglycemia triggers a cascade of biochemical processes, including increased oxidative stress, inflammation, activation of vascular endothelial growth factor (VEGF), cellular dysfunction, and apoptosis, with breakdown of the blood-retinal barriers and fluid accumulation within the macular area. Early diagnosis and appropriate management of DME are crucial for improving visual outcomes. Although the control of systemic risk factors still remains the most important strategy in DME treatment, intravitreal pharmacotherapy with anti-VEGF molecules or steroids is currently considered the first-line approach in DME patients, whereas macular laser photocoagulation and pars plana vitrectomy may be useful in selected cases. Available intravitreal steroids, including triamcinolone acetonide injections and dexamethasone and fluocinolone acetonide implants, exert their therapeutic effect by reducing inflammation, inhibiting VEGF expression, stabilizing the blood-retinal barrier and thus reducing vascular permeability. They have been demonstrated to be effective in reducing macular edema and improving visual outcomes in DME patients but are associated with a high risk of intraocular pressure elevation and cataract development, so their use requires an accurate patient selection. This manuscript aims to provide a comprehensive overview of the pathology, epidemiology, risk factors, physiopathology, clinical features, treatment mechanisms of actions, treatment options, prognosis, and ongoing clinical studies related to the treatment of DME, with particular consideration of intravitreal steroids therapy.
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Affiliation(s)
- Maria Letizia Salvetat
- Department of Ophthalmology, Azienda Sanitaria Friuli Occidentale, 33170 Pordenone, Italy; (M.L.S.)
| | - Francesco Pellegrini
- Department of Ophthalmology, Azienda Sanitaria Friuli Occidentale, 33170 Pordenone, Italy; (M.L.S.)
| | - Leopoldo Spadea
- Eye Clinic, Policlinico Umberto I, “Sapienza” University of Rome, 00142 Rome, Italy
| | - Carlo Salati
- Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy
| | - Mutali Musa
- Department of Optometry, University of Benin, Benin City 300238, Edo State, Nigeria
| | - Caterina Gagliano
- Faculty of Medicine and Surgery, University of Enna “Kore”, Piazza dell’Università, 94100 Enna, Italy
- Eye Clinic, Catania University, San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy
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13
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Lee HJ, Bae K, Yoon CK, Park UC, Park KH, Lee EK. The effect of glycosylated hemoglobin levels on the response to intravitreal dexamethasone implant for treating diabetic macular edema. Sci Rep 2024; 14:4690. [PMID: 38409191 PMCID: PMC10897127 DOI: 10.1038/s41598-024-55078-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 02/20/2024] [Indexed: 02/28/2024] Open
Abstract
This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was - 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.
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Affiliation(s)
- Hyuk Jun Lee
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, #101, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea
| | - Kunho Bae
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, #101, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea
| | - Chang Ki Yoon
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, #101, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea
| | - Un Chul Park
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, #101, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea
| | - Kyu Hyung Park
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, #101, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea
| | - Eun Kyoung Lee
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, #101, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea.
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14
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Kang EYC, Shao SC, Chang KC, Garg SJ, Lin TY, Chen KJ, Wu WC, Lai CC, Hwang YS, Lai ECC. Real-world effectiveness of intravitreal dexamethasone implants - Comparison between eyes eligible and ineligible for clinical trials and their associated outcomes. Biomed J 2024; 47:100607. [PMID: 37196877 PMCID: PMC10826172 DOI: 10.1016/j.bj.2023.100607] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/04/2023] [Accepted: 05/13/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND Concerns about the generalizability of pivotal randomized controlled trials (pRCTs) findings have been raised. We aimed to compare intravitreal dexamethasone implants' (IDIs) effectiveness for diabetic macular edema (DME) and central retinal vein occlusion (CRVO), between eyes eligible and ineligible for pRCTs. METHODS This retrospective cohort study analyzed Taiwan's Chang Gung Research Database, including DME or CRVO eyes initiating IDIs during 2015-2020. We classified all treated eyes as eligible or ineligible for pRCTs following major selection criteria of the MEAD and GENEVA trials, and evaluated three-, six-, and twelve-month changes in central retinal thickness (CRT) and visual acuity (VA) after initiating IDIs. RESULTS We included 177 IDI-treated eyes (DME: 72.3%; CRVO: 27.7%), of which 39.8% and 55.1% were ineligible for DME and CRVO pRCTs, respectively. LogMAR-VA and CRT changes at different times were comparable in DME eyes eligible (LogMAR-VA difference: 0.11 to 0.16; CRT difference: -32.7 to -96.9 μm) and ineligible (LogMAR-VA difference: -0.01 to 0.15; CRT difference: -54.5 to -109.3 μm) for the MEAD trial. By contrast, CRVO eyes ineligible for the GENEVA trial had greater LogMAR-VA changes (0.37 ~ 0.50) than those eligible (0.05 ~ 0.13), with comparable CRT reductions (eligible eyes: -72.3 to -106.4 μm; ineligible eyes: -61.8 to -110.7 μm) (all p-values <0.05 of the mean differences between eligible and ineligible CRVO eyes for all follow-ups). CONCLUSIONS IDIs had similar VA and CRT outcomes among DME eyes, regardless of pRCT-eligibility. However, among CRVO eyes, those ineligible for pRCTs showed greater deterioration in VA than those eligible.
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Affiliation(s)
- Eugene Yu-Chuan Kang
- Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shih-Chieh Shao
- Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Kai-Cheng Chang
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacy, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Sunir J Garg
- MidAtlantic Retina, The Retina Service of Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA
| | - Tzu-Yi Lin
- Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Kuan-Jen Chen
- Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Chi Wu
- Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Chun Lai
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Yih-Shiou Hwang
- Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Jen-Ai Hospital Dali Branch, Taichung, Taiwan
| | - Edward Chia-Cheng Lai
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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15
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Sanders FWB, Dumont Jones R, Jones DR, Phillips SV, Williams GS. Treatment of Diabetic Macular Edema or Macular Edema Following Retinal Vein Occlusion Based on Repeated Injection of the Dexamethasone Intravitreal Implant: A Retrospective Real-World Analysis. Clin Ophthalmol 2023; 17:3177-3187. [PMID: 37901284 PMCID: PMC10612511 DOI: 10.2147/opth.s402142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 10/11/2023] [Indexed: 10/31/2023] Open
Abstract
Purpose To assess the "real world" utility of repeated injection with the dexamethasone intravitreal implant (DEX) in routine practice. Methods This was a retrospective, single-center analysis of consecutive patients with diabetic macular edema, or macular edema following retinal vein occlusion, treated with DEX. None had received prior intravitreal steroid treatment. DEX was implanted as per the manufacturer's instructions. Results Seventy-eight individuals (95 eyes) were included (50.0% female; mean age: 68.1 ± 12.4 years; mean duration of macular edema: 13.2 ± 12.9 months). Thirty-three eyes (34.7%) had received previous treatment with an anti-vascular endothelial growth factor (anti-VEGF) and/or laser. Thirty eyes (31.6%) underwent one round of DEX implantation; the remainder received 2-5 cycles (total: 225 cycles). Initial DEX treatment led to significant increases in visual acuity (VA) at 6 weeks (mean change: 4.6 letters; P=0.004). Greater VA improvements during the first treatment cycle were associated with inferior baseline VA (P=0.02), borderline associated with baseline central macular thickness (CMT; P=0.06), and independent of prior anti-VEGF treatment (P=0.39). In an analysis of all DEX injections, VA improvements were robust across cycles 1 and 2 but reduced in cycle 3 (P=0.03). CMT improvements did not differ based on injection number (P=0.20). Increases in intraocular pressure (IOP) were largest over the first 6 weeks (but rebounded towards baseline more rapidly) in cycle 1 versus cycles 2 and 3 (P<0.001). IOP rises were typically manageable with topical medications. Conclusion This analysis confirms the broad utility of DEX and may inform decision-making in routine practice.
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Affiliation(s)
| | | | - David R Jones
- Department of Ophthalmology, Singleton Hospital, Swansea, UK
| | - Sean V Phillips
- Department of Ophthalmology, Singleton Hospital, Swansea, UK
| | - Gwyn S Williams
- Department of Ophthalmology, Singleton Hospital, Swansea, UK
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16
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Wu KY, Tan K, Akbar D, Choulakian MY, Tran SD. A New Era in Ocular Therapeutics: Advanced Drug Delivery Systems for Uveitis and Neuro-Ophthalmologic Conditions. Pharmaceutics 2023; 15:1952. [PMID: 37514137 PMCID: PMC10385446 DOI: 10.3390/pharmaceutics15071952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/10/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023] Open
Abstract
The eye's intricate anatomical barriers pose significant challenges to the penetration, residence time, and bioavailability of topically applied medications, particularly in managing uveitis and neuro-ophthalmologic conditions. Addressing this issue, polymeric nano-based drug delivery systems (DDS) have surfaced as a promising solution. These systems enhance drug bioavailability in hard-to-reach target tissues, extend residence time within ocular tissues, and utilize biodegradable and nanosized polymers to reduce undesirable side effects. Thus, they have stimulated substantial interest in crafting innovative treatments for uveitis and neuro-ophthalmologic diseases. This review provides a comprehensive exploration of polymeric nano-based DDS used for managing these conditions. We discuss the present therapeutic hurdles posed by these diseases and explore the potential role of various biopolymers in broadening our treatment repertoire. Our study incorporates a detailed literature review of preclinical and clinical studies from 2017 to 2023. Owing to advancements in polymer science, ocular DDS has made rapid strides, showing tremendous potential to revolutionize the treatment of patients with uveitis and neuro-ophthalmologic disorders.
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Affiliation(s)
- Kevin Y Wu
- Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC J1G 2E8, Canada
| | - Kenneth Tan
- Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3T 1J4, Canada
| | - Dania Akbar
- Department of Human Biology, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Mazen Y Choulakian
- Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC J1G 2E8, Canada
| | - Simon D Tran
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 1G1, Canada
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Kodjikian L, Delcourt C, Creuzot-Garcher C, Massin P, Conrath J, Velard MÈ, Lassalle T, Pinchinat S, Dupont-Benjamin L. Prospective, Observational, Multicenter, Real-World Study of the Efficacy, Safety, and Pattern of Use of the Dexamethasone Intravitreal Implant in Diabetic Macular Edema in France: Short-Term Outcomes of LOUVRE 3. Ophthalmol Ther 2023; 12:1671-1692. [PMID: 36967448 PMCID: PMC10164204 DOI: 10.1007/s40123-023-00662-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 01/19/2023] [Indexed: 03/29/2023] Open
Abstract
INTRODUCTION To evaluate real-world efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in diabetic macular edema (DME) in France. METHODS In this prospective, multicenter, observational, noncomparative, post-reimbursement study, consecutively enrolled patients with DME had a baseline evaluation on day 0. Those treated with DEX on day 0 were to be reevaluated at week 6 and months 6, 12, 18, and 24. DEX retreatment and/or alternative therapies were allowed during follow-up. The primary outcome measure was the maximum best corrected visual acuity (BCVA) gain from baseline during follow-up. Secondary outcome measures included time to maximum BCVA gain, patients (%) with prespecified BCVA gains from baseline at each visit, maximum central retinal thickness (CRT) reduction from baseline, patients (%) with CRT reduction ≥ 20% from baseline at each visit, patients (%) with DME resolution (per investigator judgement), and adverse events (AEs). RESULTS Of 112 patients/eyes with DME for 3.5 years (mean) at baseline, 80 (including 86.1% previously treated) received DEX on day 0 and were analyzed for efficacy. Early study termination precluded collection of ≥ 12-month efficacy data. Patients received 1.4 DEX injections over 8.3 months (averages). The maximum BCVA gain from baseline was 3.6 letters, reached after 77.2 days (averages); 24.6% (week 6) and 15.0% (month 6) of patients experienced ≥ 10-letter BCVA gains from baseline. The mean maximum CRT reduction from baseline was -146.4 µm; 61.4% (week 6) and 36.0% (month 6) of patients had CRT reductions ≥ 20% from baseline, and 68.1% reported DME resolution at least once during follow-up. Ocular hypertension (n = 8, 12.1%) was the most frequent treatment-related AE. CONCLUSIONS LOUVRE 3 confirmed that DEX improves BCVA and CRT, even in a patient population that had predominantly received DEX before enrollment in the study, and showed that DME resolution was observed during follow-up. DEX tolerability was consistent with published data, supporting treatment benefits in DME. CLINICALTRIALS GOV IDENTIFIER NCT03003416.
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Affiliation(s)
- Laurent Kodjikian
- La Croix-Rousse Hospital, University Hospital of Lyon, 103 Grande Rue de La Croix-Rousse, 69004, Lyon, France.
- UMR CNRS 5510 MATEIS INSA Lyon, Université de Lyon Claude Bernard, Lyon, France.
| | - Cécile Delcourt
- Université de Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France
| | | | - Pascale Massin
- Centre Hospitalier de L'Université de Lariboisière, Paris, France
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Hertzberg SNW, Moe MC, Jørstad ØK, Petrovski BÉ, Burger E, Petrovski G. Healthcare expenditure of intravitreal anti-vascular endothelial growth factor inhibitors compared with dexamethasone implant for diabetic macular oedema. Acta Ophthalmol 2022; 100:e1630-e1640. [PMID: 35467793 PMCID: PMC9790387 DOI: 10.1111/aos.15151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 03/19/2022] [Accepted: 03/24/2022] [Indexed: 12/30/2022]
Abstract
PURPOSE The aim of this study was to estimate the 1-year costs associated with treating diabetic macular oedema (DME) patients using current intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics compared with the dexamethasone implant. METHODS We conducted a descriptive cost-evaluation analysis using data from Oslo University Hospital and literature to compare three different intravitreal drugs for DME: bevacizumab, aflibercept and dexamethasone. Stratification of patients into 'Naive' or 'Switch' group was based on treatment history. We estimated the costs from healthcare and 'extended' healthcare perspectives. Sensitivity analysis evaluated the impact of various parameters. RESULTS The average injections per patient per year for the Naive group (bevacizumab), Switch group (aflibercept) and dexamethasone were 9.5, 9.1 and 3.0 respectively. From a healthcare perspective, the 1-year costs for the Naive group were 15% lower (bevacizumab, €3619), and for the Switch group, 23% higher (aflibercept, €5226) compared with dexamethasone (€4252). The 'extended' healthcare perspective showed the cost per patient per year for bevacizumab remained nominally lower in the Naive group, while dexamethasone remained lower for the Switch group (€5116 for dexamethasone, compared to €4987 for bevacizumab and €6537 for aflibercept). CONCLUSIONS From a primary healthcare perspective, the dexamethasone as a first-line DME treatment may increase economic costs in settings where bevacizumab is used off-label. Treating resistant DMEwith dexamethasone may reduce the costs and treatment burden compared with switching to aflibercept.
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Affiliation(s)
- Silvia NW Hertzberg
- Department of Ophthalmology, Faculty of Medicine, Center for Eye Research, Oslo University Hospital and Institute for Clinical MedicineUniversity of OsloOsloNorway
| | - Morten Carstens Moe
- Department of Ophthalmology, Faculty of Medicine, Center for Eye Research, Oslo University Hospital and Institute for Clinical MedicineUniversity of OsloOsloNorway
| | - Øystein Kalsnes Jørstad
- Department of Ophthalmology, Faculty of Medicine, Center for Eye Research, Oslo University Hospital and Institute for Clinical MedicineUniversity of OsloOsloNorway
| | - Beáta Éva Petrovski
- Department of Ophthalmology, Faculty of Medicine, Center for Eye Research, Oslo University Hospital and Institute for Clinical MedicineUniversity of OsloOsloNorway
| | - Emily Burger
- Department of Health Management and Health EconomicsUniversity of OsloOsloNorway,Center for Health Decision ScienceHarvard T. H. Chan School of Public HealthBostonMAUSA
| | - Goran Petrovski
- Department of Ophthalmology, Faculty of Medicine, Center for Eye Research, Oslo University Hospital and Institute for Clinical MedicineUniversity of OsloOsloNorway
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Nikolopoulou E, Sacconi R, Lorusso M, Costanzo E, Parravano M, Micelli Ferrari L, Ferrari TM, Querques G. Effect of intravitreal dexamethasone implant in treatment-naive and previously-treated patients with diabetic macular edema. Eur J Ophthalmol 2022; 33:11206721221143166. [PMID: 36457210 DOI: 10.1177/11206721221143166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
PURPOSE To document the effects of intravitreal dexamethasone implant on retinal microvasculature in patients with diabetic retinopathy complicated by center-involving macular edema. METHODS 35 eyes of 35 patients affected by retinopathy due to type 2 diabetes (15 treatment-naïve and 20 previously treated) were included in this retrospective study with a follow-up of 4 months. Foveal avascular zone (FAZ) area and superficial capillary plexus (SCP) and deep capillary plexus (DCP) densities in the foveal and parafoveal areas were measured by optical coherence tomography angiography (OCTA) at baseline and 2 and 4 months post-injection. Intraocular pressure, morphological and functional parameters were evaluated. RESULTS a significant difference was found in both groups at 2 months after injection in terms of functional (BCVA, p < 0.05) and morphological (CMT, p < 0.05) parameters. During follow-up, FAZ area, SCP, and DCP in the foveal and parafoveal areas did not change significantly. CONCLUSIONS intravitreal dexamethasone implant is effective in the treatment of diabetic center-involving macular edema and was associated with significant improvements in BCVA and CMT at 2 months after injection. After a single dexamethasone implant injection, FAZ area and retinal vascular density does not show significant variations in both naive and non-naive DME patients subgroups.
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Affiliation(s)
- Eleni Nikolopoulou
- Department of Ophthalmology, 161123Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli", Bari, Italy
| | - Riccardo Sacconi
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of head and neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Lorusso
- Department of Ophthalmology, 161123Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli", Bari, Italy
| | | | | | - Luisa Micelli Ferrari
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, "Aldo Moro" University of Bari, Bari, Italy
| | - Tommaso Micelli Ferrari
- Department of Ophthalmology, 161123Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli", Bari, Italy
| | - Giuseppe Querques
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of head and neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
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20
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Lee K, Lee G, Lee S, Park CY. Advances in ophthalmic drug delivery technology for postoperative management after cataract surgery. Expert Opin Drug Deliv 2022; 19:945-964. [PMID: 35917497 DOI: 10.1080/17425247.2022.2109624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Cataract surgery is becoming more common due to an aging world population. Intraocular lenses and surgical technique have developed remarkably recently, but the development of postoperative medication to prevent postsurgery complications has been relatively delayed. We still largely depend on eye drops for the management of post-cataract-surgery patients. Mental and physical problems that often occur in elderly cataract patients make it difficult for patients to apply eye drops by themselves. It is necessary to develop new effective drug delivery methods. AREAS COVERED This updated review article provides a brief review of why drug management is needed following cataract surgery and an overview of current developments in new drug delivery methods for ophthalmic treatment. In particular, various novel drug delivery methods that can be used for post-cataract-surgery management and their current development stages are extensively reviewed. EXPERT OPINION Rapidly developing technologies, such as intraocular and external ophthalmic implants, polymers, and nanotechnology, are being actively applied to develop novel drug delivery systems for safe and effective management after cataract surgery. Their goal is to achieve sufficient drug release for the desired duration with a single application. These will largely replace the inconvenience of eye drops for elderly patients in the future.
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Affiliation(s)
- Kangmin Lee
- Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South Korea
| | - Gahye Lee
- Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South Korea
| | - Soomin Lee
- Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South Korea
| | - Choul Yong Park
- Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South Korea
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21
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Herold TR, Vounotrypidis E, Liegl R, Koenig SF, Priglinger SG, Wolf A. LONG-TERM EFFICACY OF FLUOCINOLONE IN EYES WITH IRIS-LENS DIAPHRAGM DISRUPTION AND PCME WITH MEDICATION FIXED IN THE SCLERA (MEFISTO). Retina 2022; 42:1392-1398. [PMID: 35321998 PMCID: PMC9200227 DOI: 10.1097/iae.0000000000003472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE The aim of our prospective off-label, interventional clinical trial was to evaluate the efficacy and safety of the fluocinolone-loop-anchoring technique over two years in eyes with iris-lens diaphragm disruption and pseudophakic cystoid macular edema. METHODS In 10 eyes, scleral fixation of fluocinolone implant was performed. Main outcome measures were the development of best-corrected visual acuity (BCVA), central retinal thickness over 24 months, and general safety of the procedure. RESULTS A significant improvement to 0.57 ± 0.38 log MAR (Snellen 20/80) (range 0-1.30) was observed (P = 0.003) at 1 month. Further improvement to 0.45 ± 036 log MAR (Snellen 20/60) was observed until month 18 (P = 0.081). Mean central retinal thickness decreased by 22% from 601.6 ± 235.5 µm to 449.1 ± 128.9 µm at 1 month. In one patient, the implant has to be removed at Month 7 because of elevated intraocular pressure and one patient after globe rupture had a retinal redetachment at Month 4. CONCLUSION In this study, we showed that the treatment of recalcitrant pseudophakic cystoid macular edema with scleral fixated fluocinolone implant in eyes with disruption of the iris-lens diaphragm provides good anatomical and functional results with a reasonable safety profile over 24 months in eyes where pseudophakic cystoid macular edema is otherwise difficult to treat and often left untreated.
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Affiliation(s)
- Tina R. Herold
- Department of Ophthalmology, University Hospital, LMU Munich, Germany
| | | | - Raffael Liegl
- Department of Ophthalmology, University Hospital, Bonn, Germany; and
| | - Susanna F. Koenig
- Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
| | | | - Armin Wolf
- Department of Ophthalmology, University Hospital, Ulm, Germany
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22
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Chou HD, Wu CH, Chiang WY, Chen NN, Hwang YS, Chen KJ, Lai CH, Wu PC, Chen YH, Yeung L, Shao SC, Lai CC, Wu WC. Optical coherence tomography and imaging biomarkers as outcome predictors in diabetic macular edema treated with dexamethasone implant. Sci Rep 2022; 12:3872. [PMID: 35264625 PMCID: PMC8907275 DOI: 10.1038/s41598-022-07604-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 02/17/2022] [Indexed: 11/09/2022] Open
Abstract
In this retrospective, multicenter study, we determined the predictive value of imaging biomarkers in diabetic macular edema (DME) outcomes following dexamethasone (DEX) implant(s). Sixty-seven eyes of 47 patients' best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography (OCT) before and after intravitreal DEX implants were evaluated. Baseline imaging biomarkers were graded using fundus photography and OCT, and the predictive value of biomarkers for significant treatment effects at six months was analyzed. Six months after 2.0 ± 0.8 (mean ± SD) DEX implants, 35 (52%) and 16 (24%) eyes had CFT reduction ≥ 10% from baseline and decreased to < 300 µm, respectively. BCVA improved ≥ 3 lines in 15 (22%) and remained stable in 38 (57%) eyes. At six months, eyes with severe intraretinal cyst (IRC), abundant hyperreflective dots (HRD), and moderate or severe hard exudate had a significantly higher chance of CFT reduction ≥ 10%. Eyes with abundant HRD at baseline and those underwent three DEX implants were more likely to achieve CFT < 300 µm. Eyes with DME and severe IRC, abundant HRD, or moderate-to-severe hard exudate at baseline were more likely to show a significant reduction in CFT six months after DEX implant.
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Affiliation(s)
- Hung-Da Chou
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fuxing St., Gueishan Dist., Taoyuan City, 333, Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Cheng-Hsiu Wu
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan.,Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
| | - Wei-Yu Chiang
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan.,Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
| | - Nan-Ni Chen
- Department of Ophthalmology, Chiayi Chang Gung Memorial Hospital, Chiayi City, Taiwan
| | - Yih-Shiou Hwang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fuxing St., Gueishan Dist., Taoyuan City, 333, Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan.,Department of Ophthalmology, Chang Gung Memorial Hospital, Xiamen Branch, Xiamen, China.,Department of Ophthalmology, Jen-Ai Hospital Dali Branch, Taichung, Taiwan
| | - Kuan-Jen Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fuxing St., Gueishan Dist., Taoyuan City, 333, Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Chien-Hsiung Lai
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan.,Department of Ophthalmology, Chiayi Chang Gung Memorial Hospital, Chiayi City, Taiwan.,Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.,School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Pei-Chang Wu
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan.,Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
| | - Yi-Hao Chen
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan.,Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
| | - Ling Yeung
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan.,Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
| | - Shih-Chieh Shao
- Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
| | - Chi-Chun Lai
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan.,Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fuxing St., Gueishan Dist., Taoyuan City, 333, Taiwan. .,College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
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23
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Goñi FJ, Barton K, Dias JA, Diestelhorst M, Garcia-Feijoo J, Hommer A, Kodjikian L, Nicolò M. Intravitreal Corticosteroid Implantation in Diabetic Macular Edema: Updated European Consensus Guidance on Monitoring and Managing Intraocular Pressure. Ophthalmol Ther 2022; 11:15-34. [PMID: 34993882 PMCID: PMC8770785 DOI: 10.1007/s40123-021-00427-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 11/08/2021] [Indexed: 12/13/2022] Open
Abstract
Intravitreal therapy for diabetic macular edema can, in susceptible patients, increase intraocular pressure (IOP). As uncontrolled IOP can potentially be sight threatening, monitoring is an essential component of patient management. It can be challenging for retina specialists to ensure that monitoring is rigorous enough to detect and resolve any potential problems at the earliest opportunity without it also being overburdensome for patients who have the lowest risk of developing an IOP rise. We have developed dynamic algorithms that: (1) tailor the frequency and extent of monitoring according to individual susceptibility and current IOP and (2) assist retina specialists in deciding when they should consider a referral to a glaucoma specialist. One algorithm is for patients with a relatively low susceptibility to developing an IOP rise (those whose baseline IOP is < 22 mmHg and who do not have a history of IOP events). Depending on their first post-implantation IOP check, the algorithm classifies them as: low risk if IOP remains < 22 mmHg; medium risk if IOP is 22-25 mmHg and any rise from baseline is < 10 mmHg; or high risk if IOP is > 25 mmHg or any rise from baseline is ≥ 10 mmHg. Thereafter, the algorithm guides on the frequency and extent of monitoring required in each of these groups and, if IOP rises or falls during treatment, patients may move up or down the risk groups accordingly. A different algorithm is provided for patients who are more susceptible to developing an IOP rise (those with a baseline IOP of ≥ 22 mmHg or a prior history of an IOP event). These patients need monitoring more closely so this algorithm has only medium- or high-risk classifications. These algorithms update the previous monitoring guidance by Goñi et al. (Goñi et al. in Ophthalmol Ther 5:47-61, 2016).
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Affiliation(s)
- Francisco J. Goñi
- Ophthalmology Department, Mollet Hospital, Ronda dels Pinetons 6, 08100 Mollet del Vallès, Barcelona, Spain
| | - Keith Barton
- Glaucoma Service, Moorfields Eye Hospital, London, UK
| | | | | | - Julián Garcia-Feijoo
- Ophthalmology Department, Complutense University, San Carlos Hospital, Madrid, Spain
| | | | - Laurent Kodjikian
- Department of Ophthalmology, Croix-Rousse University Hospital, Lyon, France
- UMR-CNRS 5510 Matéis, University Lyon 1, Villeurbane, France
| | - Massimo Nicolò
- University Eye Clinic, DINOGMI, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
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24
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Wang D, Wang H, Wu S, Yang X, Xu J. Intravitreal Ranibizumab Alone or in Combination with Calcium Dobesilate for the Treatment of Diabetic Macular Edema in Nonproliferative Diabetic Retinopathy Patients: 12-Month Outcomes of a Retrospective Study. Int J Clin Pract 2022; 2022:6725225. [PMID: 36340967 PMCID: PMC9613393 DOI: 10.1155/2022/6725225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/29/2022] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE This study investigates the efficacy of CaD combined with intravitreal ranibizumab for the treatment of diabetic macular edema (DME) in patients with nonproliferative DR. METHODS This retrospective, observational, case-control study enrolled consecutive patients newly diagnosed with DME. The patients were treated with 3-monthly loading dose injections of intravitreal ranibizumab (IVR) followed by pro re nata injections (3 + PRN), with or without daily oral CaD. The patients were treated and followed up for 12 months. We reviewed their medical records to determine the optical coherence tomography (OCT) findings, number of injections, best-corrected visual acuity (BCVA), and central macular thickness (CMT) at 3, 6, and 12 months after the first injection. RESULTS We reviewed 102 eyes of 102 patients; 54 patients received IVR combined with oral CaD (IVR + CaD group) and 48 received only IVR (IVR group). In both groups, BCVA was higher, and CMT was lower, at 3, 6, and 12 months after the injection compared to those at the baseline (p < 0.05 for all), while there were no significant differences in BCVA improvement or CMT reduction between the two groups (p > 0.05). The mean number of IVR injections was significantly lower in the IVR + CaD group than the IVR group (5.4 ± 1.1 vs. 6.7 ± 1.6 injections, p < 0.05) during 1 year of treatment. No adverse events were noted in either group. CONCLUSIONS Compared to IVR alone, the addition of oral CaD to IVR in DME patients was safe and effective for improving visual function and restoring the retinal anatomy and was associated with the need for fewer injections.
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Affiliation(s)
- Dongxuan Wang
- Department of Ophthalmology, Changyi People's Hospital, Changyi, Weifang 261399, Shandong, China
| | - Hui Wang
- Department of Ophthalmology, Changyi People's Hospital, Changyi, Weifang 261399, Shandong, China
| | - Shuang Wu
- Department of Ophthalmology, Changyi People's Hospital, Changyi, Weifang 261399, Shandong, China
| | - Xueqiu Yang
- Department of Ophthalmology, Changyi People's Hospital, Changyi, Weifang 261399, Shandong, China
| | - Jiansen Xu
- Department of Ophthalmology, Changyi People's Hospital, Changyi, Weifang 261399, Shandong, China
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25
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Meng Z, Chen Y, Wu W, Yan B, Meng Y, Liang Y, Yao X, Luo J. Exploring the Immune Infiltration Landscape and M2 Macrophage-Related Biomarkers of Proliferative Diabetic Retinopathy. Front Endocrinol (Lausanne) 2022; 13:841813. [PMID: 35692390 PMCID: PMC9186015 DOI: 10.3389/fendo.2022.841813] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 04/19/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUNDS Diabetic retinopathy (DR), especially proliferative diabetic retinopathy (PDR), is the major cause of irreversible blindness in the working-age population. Increasing evidence indicates that immune cells and the inflammatory microenvironment play an important role during PDR development. Herein, we aim to explore the immune landscape of PDR and then identify potential biomarkers correlated with specific infiltrating immune cells. METHODS We mined and re-analyzed PDR-related datasets from the Gene Expression Omnibus (GEO) database. Using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm, we investigated the infiltration of 22 types of immune cells in all selected samples; analyses of differences and correlations between infiltrating cells were used to reveal the immune landscape of PDR. Thereafter, weighted gene co-expression network analysis (WGCNA) and differential expression analysis were applied to identify the hub genes on M2 macrophages that may affect PDR progression. RESULTS Significant differences were found between infiltration levels of immune cells in fibrovascular membranes (FVMs) from PDR and normal retinas. The percentages of follicular helper T cells, M1 macrophages, and M2 macrophages were increased significantly in FVMs. Integrative analysis combining the differential expression and co-expression revealed the M2 macrophage-related hub genes in PDR. Among these, COL5A2, CALD1, COL6A3, CORO1C, and CALU showed increased expression in FVM and may be potential biomarkers for PDR. CONCLUSIONS Our findings provide novel insights into the immune mechanisms involved in PDR. COL5A2, CALD1, COL6A3, CORO1C, and CALU are M2 macrophage-related biomarkers, further study of these genes could inform novel ideas and basis for the understanding of disease progression and targeted treatment of PDR.
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Affiliation(s)
- Zhishang Meng
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yanzhu Chen
- Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Wenyi Wu
- Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China
| | - Bin Yan
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yongan Meng
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Youling Liang
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiaoxi Yao
- Shenzhen College of International Education, Shenzhen, China
| | - Jing Luo
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Jing Luo,
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26
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Udaondo P, Hervas-Ontiveros A, Rosemblatt A, Garcia-Delpech S. Impact of Different Clinical Baseline Characteristics on Intravitreal Dexamethasone Implant Ozurdex ® Outcomes. Clin Ophthalmol 2021; 15:4153-4162. [PMID: 34703201 PMCID: PMC8524257 DOI: 10.2147/opth.s336865] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 10/06/2021] [Indexed: 11/23/2022] Open
Abstract
Purpose To determine the impact of different baseline clinical characteristics on the improvement in best corrected visual acuity (BCVA) in patients with diabetic macular edema (DME) who underwent the intravitreal dexamethasone implant (DEX) Ozurdex®. Methods This was a single center retrospective study conducted on patients with DME, either naïve or previously treated, who were treated with one or more DEX and had a follow-up of at least 6 months. The main outcome measure was the proportion of DEX achieving an improvement ≥15 letters in BCVA. Results The study analyzed 192 DEX implants administered to 97 eyes (65 patients). Among the 192 DEX analyzed, 57 (29.7%) implants achieved a BCVA improvement ≥15 letters (ETDRS) from baseline, with a mean time for achieving such improvement of 89.2 (39.7) days. Eyes who received an additional DEX and those with a duration of DME < 6 months had a greater probability of achieving a BCVA improvement ≥15 letters (odds-ratio: 2.55, p = 0.0028 and odds-ratio: 1.93, p = 0.0434). The mean (standard deviation) change in BCVA from baseline was 7.5 (14.5) letters, p < 0.0001. The mean change in central macular thickness (CMT) from baseline was -128.0 (151.0) µm, p < 0.0001. The mean number of DEX implanted was 1.9 (0.8). Four (2.1%) DEX experienced an intraocular pressure increased ≥10 mm Hg; all the cases were successfully managed with topical antiglaucoma medication. Conclusion The results of this study confirmed previous evidence suggesting that DEX is effective for improving BCVA and CMT in patients with DME.
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Affiliation(s)
- Patricia Udaondo
- Ophthalmology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain.,Aiken Prevencción y Cirugía Ocular, Valencia, Spain
| | - Ana Hervas-Ontiveros
- Ophthalmology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain.,Aiken Prevencción y Cirugía Ocular, Valencia, Spain
| | - Amir Rosemblatt
- Department of Ophthalmology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Salvador Garcia-Delpech
- Ophthalmology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain.,Aiken Prevencción y Cirugía Ocular, Valencia, Spain
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27
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Comparison of the 1-Year Visual and Anatomical Outcomes between Subthreshold Red (670 nm) and Yellow (577 nm) Micro-Pulse Laser Treatment for Diabetic Macular Edema. Pharmaceuticals (Basel) 2021; 14:ph14111100. [PMID: 34832882 PMCID: PMC8625374 DOI: 10.3390/ph14111100] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 11/17/2022] Open
Abstract
We investigated the efficacy and safety of red (670 nm) subthreshold micropulse laser (SMPL) treatment for diabetic macular edema (DME) and compared the 1-year treatment outcomes of red and yellow (577 nm) SMPL for DME. A medical chart review was performed in 43 consecutive eyes of 35 patients who underwent red or yellow SMPL treatment for DME and were followed up for 12 months. There were 26 and 17 eyes in the yellow and red SMPL groups, respectively. The mean best-corrected visual acuity (BCVA) was maintained throughout the follow-up period of 12 months in the yellow and red SMPL groups (p = 0.39, p = 0.70, respectively). The central retinal thickness (CRT) measured by spectral-domain optical coherence tomography (SD-OCT) was significantly decreased at 12 months from baseline in the yellow and red SMPL groups (p = 0.047, p = 0.03, respectively). Although the amount of CRT reduction in the red SMPL group was significantly greater than that in the yellow SMPL group at 8 months from baseline (p = 0.02), the significance disappeared at the final follow-up period (p = 0.44). The red SMPL maintained the BCVA in patients with center-involving DME. The mean CRT in the red SMPL group significantly decreased, and the amount of CRT reduction was equivalent to that in the yellow SMPL group.
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28
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Wei W, Chen Y, Hu B, Zhao M, Han M, Dai H, Uy HS, Chen MY, Wang K, Jiao J, Lou J, Li XY. Multicenter, Prospective, Randomized Study of Dexamethasone Intravitreal Implant in Patients with Center-Involved Diabetic Macular Edema in the Asia-Pacific Region. Clin Ophthalmol 2021; 15:4097-4108. [PMID: 34675477 PMCID: PMC8520964 DOI: 10.2147/opth.s325618] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Accepted: 09/08/2021] [Indexed: 11/23/2022] Open
Abstract
Purpose To evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) compared with laser photocoagulation in patients with diabetic macular edema (DME). Patients and Methods This Phase 3, multicenter, randomized, efficacy evaluator–masked, parallel-group, 12-month clinical study enrolled adults in China and the Philippines with reduced visual acuity secondary to fovea-involved DME in the study eye. Participants were randomized 1:1 to study eye treatment with laser photocoagulation every 3 months as needed (n = 139) or DEX every 5 months (n = 145). The main efficacy measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT), and leakage area. The primary endpoint was the average change in BCVA from baseline over 12 months (area-under-the-curve method). Preplanned subgroup analyses evaluated outcomes in Chinese patients. Results Mean average change in BCVA from baseline during the study (letters) was 4.3 with DEX (n = 145) versus 1.4 with laser (n = 127) overall (P = 0.001) and 4.6 with DEX (n = 129) versus 0.6 with laser (n = 113) in Chinese patients (P < 0.001). At Month 12, mean change in CRT from baseline was −209.5 μm with DEX versus −120.3 μm with laser (P < 0.001) and mean change in total leakage area from baseline was −8.367 mm2 with DEX versus −0.637 mm2 with laser (P < 0.001). The most common treatment-emergent adverse events in the DEX group were increased intraocular pressure and cataract. Conclusion DEX administered every 5 months provided significantly greater improvement in BCVA, CRT, and total leakage area compared with laser treatment. DEX demonstrated an acceptable safety profile, consistent with an intraocular corticosteroid, and similar to that reported in completed global registration studies.
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Affiliation(s)
- Wenbin Wei
- Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Youxin Chen
- Peking Union Medical College Hospital, Beijing, People's Republic of China
| | - Bojie Hu
- Tianjin Medical University Eye Hospital, Tianjin, People's Republic of China
| | - Mingwei Zhao
- Peking University People's Hospital, Beijing, People's Republic of China
| | - Mei Han
- Tianjin Eye Hospital, Tianjin, People's Republic of China
| | - Hong Dai
- Beijing Hospital, Beijing, People's Republic of China
| | - Harvey S Uy
- Peregrine Eye and Laser Institute, Makati City, Philippines
| | | | - Kate Wang
- Allergan, an AbbVie company, Irvine, CA, USA
| | - Jenny Jiao
- Allergan, an AbbVie company, Irvine, CA, USA
| | - Jean Lou
- Allergan, an AbbVie company, Irvine, CA, USA
| | - Xiao-Yan Li
- Allergan, an AbbVie company, Irvine, CA, USA
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29
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Augustin AJ, Becker MD, Hatz K, Kaymak H, Shirlaw A. Assessment of Reinjection Numbers and Intervals for Diabetic Macular Edema Patients Who Received Dexamethasone Intravitreal Implants in Germany and Switzerland. Clin Ophthalmol 2021; 15:3957-3967. [PMID: 34616140 PMCID: PMC8489531 DOI: 10.2147/opth.s315548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 08/26/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE The purpose was to assess the number and intervals of dexamethasone intravitreal implant (DEX) reinjections in a real-world setting for the treatment of diabetic macular edema (DME) and to determine the relationship with effectiveness and safety. PATIENTS AND METHODS Data were abstracted from medical records of DME patients in Germany and Switzerland for this retrospective, multicenter, drug utilization study. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes 7-12 weeks post-injection(s) measured effectiveness. Adverse events (AEs) of special interest were reported. RESULTS A total of 141 patients, 108 from Germany and 33 from Switzerland, were assessed. Mean (SD) reinjection interval was 5.7 (4.2) months. Mean baseline BCVA was 61.6 letters, and mean baseline CRT was 413.3 µm. The mean BCVA and CRT changes at 7-12 weeks after baseline, reinjection 1, 2, and 3 were +3.4, +3.7, +3.2, and -1.4 letters and -88.3, -81.6, -102.4, and -124.1 μm, respectively. The Spearman correlation between change in BCVA and CRT and DEX reinjection interval was r=0.03 (P=0.66) and r=0.07 (P=0.38), respectively. Only 18% of patients experienced at least 1 AE. CONCLUSION There was no statistically significant correlation between drug effectiveness and reinjection intervals in either country. Although these results are preliminary, they indicate that DEX improves BCVA and CRT in real-world clinical practice.
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Affiliation(s)
| | - Matthias D Becker
- Department of Ophthalmology, Zurich City Hospital, Zurich, Switzerland
- Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany
| | - Katja Hatz
- Vista Klinik Binningen, Switzerland and Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Hakan Kaymak
- MVZ Macula and Retina Center Breyer, Kaymak, Klabe, Duesseldorf, Germany
| | - Andrew Shirlaw
- Allergan, an AbbVie company, Marlow, Buckinghamshire, UK
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Intravitreal Dexamethasone Implants for Refractory Macular Edema in Eyes with Noninfectious Uveitis. J Clin Med 2021; 10:jcm10173762. [PMID: 34501209 PMCID: PMC8432099 DOI: 10.3390/jcm10173762] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/28/2021] [Accepted: 08/11/2021] [Indexed: 12/25/2022] Open
Abstract
Macular edema (ME) is a common cause of visual loss among eyes with uveitis, and its management can be challenging. Steroids are an effective treatment for ME, and intravitreal dexamethasone (DEX) implants provide sustained steroid release. The purpose of this study is to evaluate intravitreal DEX implant on refractory ME in eyes with noninfectious uveitis. A retrospective study including 52 eyes of 37 patients with refractory uveitic ME was conducted from January 2011 through August 2017 at Linkou Chang Gung Memorial Hospital in Taiwan. Patients’ demographic characteristics were collected. In addition, clinical information, including corrected visual acuity (VA), intraocular pressure (IOP), and central retinal thickness (CRT) on optical coherence tomography, was recorded and analyzed. During the study period, affected eyes received a total of 110 intravitreal DEX implants (range, one to six in each eye). After the first DEX implant injection in all eyes, VA significantly improved at one and two months. CRT significantly decreased one month after a single DEX implant, and the effect lasted for six months and waned over time. Patients receiving multiple DEX implants still showed significant decreases in CRT one month after the first implant. Increases in IOP were noted one month after the DEX implant, but the IOP could be medically controlled. Intravitreal DEX implants can effectively treat refractory uveitic ME, improving both VA and CRT with an acceptable safety profile. Further studies are necessary to evaluate the effect of multiple implants and long-term outcomes.
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Karti O, Saatci AO. Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema. World J Diabetes 2021; 12:1220-1232. [PMID: 34512888 PMCID: PMC8394236 DOI: 10.4239/wjd.v12.i8.1220] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 04/25/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic macular edema (DME) is a very important and well-known cause of visual loss in diabetics. Blood–retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the posterior pole namely DME. Even though it is not clearly understood, current evidence suggests that chronic low-grade inflammation characterized with various cytokines has a major role in the occurrence of DME. Clinical trials are continuously shaping our treatment approaches for the eyes with DME. Today, vascular endothelial growth factor (VEGF) inhibitor and steroid administrations are the main alternatives in DME treatment. Dexamethasone (DEX) implant (Ozurdex®; Allergan, Inc., Irvine, CA, United States) was approved by the United States Food & Drug Administration in 2014 for DME treatment. The implant is made up of a biodegradable solid copolymer that is broken down by releasing its active ingredient into the vitreous cavity over time. Biphasic release feature of this sustained-release drug delivery system ensures its efficacy for up to 6 mo with an acceptable and manageable safety profile. DEX implant provides a favorable anatomical and functional outcome in DME as shown in several randomized-controlled studies but has a relatively higher ocular side-effect profile such as increased risk of cataract formation and raised intraocular pressure when compared to the gold standard anti-VEGF agents. Thus, DEX implant becomes the second-line treatment option demonstrating inadequate clinical response to anti-VEGF therapy. However, it can be preferred as the first-line treatment in vitrectomized and pseudophakic eyes. Even in some selected conditions DEX implant is favored over anti-VEGF agents where the use of VEGF-inhibitors is either inappropriate or contraindicated such as the patients with a recent history of a major cardiovascular or cerebrovascular event, pregnancy and noncompliant to frequent visits. This mini-review briefly overviews the efficacy, safety profile and complications of DEX implant and summarizes the outcome of DEX implant administration in major clinical studies on DME treatment.
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Affiliation(s)
- Omer Karti
- Department of Ophthalmology, İzmir Democracy University, İzmir 35330, Turkey
| | - Ali Osman Saatci
- Department of Ophthalmology, Dokuz Eylul University, İzmir 35330, Turkey
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Muto T, Machida S. Intravitreal Fasudil for Treatment of Diabetic Macular Edema with an Unfavorable Response. Semin Ophthalmol 2021; 37:164-170. [PMID: 34384329 DOI: 10.1080/08820538.2021.1943458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
PURPOSE This study evaluates the effect of intravitreal injection of a Rho-associated protein kinase (ROCK) inhibitor, fasudil, on diabetic macular edema (DME) with an unfavorable response. METHODS This study included 14 eyes of 13 patients (mean age: 65.7 ± 5.2 years) with DME, and eligible eyes underwent single intravitreal injection of 0.025 mg fasudil. The best-corrected visual acuity (BCVA), intraocular pressure (IOP), and central macular thickness (CMT) were evaluated before and 1, 2, and 3 months after treatment. The standard automated perimetry (SAP) results and maximal response of the electroretinogram (ERG) were recorded before and 3 months after treatment. RESULTS The BCVA, IOP, and CMT remained unchanged during the study period. Similarly, the mean deviation obtained by SAP and each ERG parameter did not show significant changes after the treatment. CONCLUSIONS Although single intravitreal fasudil injection failed to show therapeutic benefits in DME, it seemed to have no negative effect on the retina.
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Affiliation(s)
- Tetsuya Muto
- Department of Ophthalmology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | - Shigeki Machida
- Department of Ophthalmology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
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Silva M, Peng T, Zhao X, Li S, Farhan M, Zheng W. Recent trends in drug-delivery systems for the treatment of diabetic retinopathy and associated fibrosis. Adv Drug Deliv Rev 2021; 173:439-460. [PMID: 33857553 DOI: 10.1016/j.addr.2021.04.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/05/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022]
Abstract
Diabetic retinopathy is a frequent microvascular complication of diabetes and a major cause of visual impairment. In advanced stages, the abnormal neovascularization can lead to fibrosis and subsequent tractional retinal detachment and blindness. The low bioavailability of the drugs at the target site imposed by the anatomic and physiologic barriers within the eye, requires long term treatments with frequent injections that often compromise patient's compliance and increase the risk of developing more complications. In recent years, much effort has been put towards the development of new drug delivery platforms aiming to enhance their permeation, to prolong their retention time at the target site and to provide a sustained release with reduced toxicity and improved efficacy. This review provides an overview of the etiology and pathophysiology of diabetic retinopathy and current treatments. It addresses the specific challenges associated to the different ocular delivery routes and provides a critical review of the most recent developments made in the drug delivery field.
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Affiliation(s)
- Marta Silva
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Tangming Peng
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Xia Zhao
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Shuai Li
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Mohd Farhan
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Wenhua Zheng
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau.
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Uzel MM, Karahan E, Koroglu Canli M, Guler C. The prognostic role of optical coherence tomography in diabetic macular edema patients undergoing early dexamethasone implant shift. Eur J Ophthalmol 2021; 32:1562-1569. [PMID: 34020568 DOI: 10.1177/11206721211019569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE To determine the prognostic characteristics of optical coherence tomography (OCT) parameters by evaluating diabetic macular edema (DME) patients with early dexamethasone (DEX) shift after three doses of intravitreal ranibizumab (RNB) injection. METHODS Fifty-four eyes of 34 patients who had DEX implant after three doses of RNB were included in this retrospective study. Early DEX shift includes patients who received direct DEX implant replacement after three doses of RNB load. Baseline OCT values and factors affecting best corrected visual acuity (BCVA) and central macular thickness (CMT) response were analyzed with logistic regression analyses. RESULTS The presence of subretinal fluid and hyperreflective spot (HRS) >20 were found to be a negative predictive factor for anatomical response. (p = 0.009, p = 0.001, respectively) Low initial BCVA creates a positive effect on visual gain.( p = 0.041) Giant outer nuclear layer cysts, completely disrupted inner segment-outer segment and HRS > 20 have a negative effect on visual gain. (p = 0.025, p = 0.043, p = 0.023, respectively) According to the receiver operating characteristic analysis, the subretinal fluid volume threshold at which >20% reduction in CMT occurs was determined to be 0.85 mm3. (sensitivity 70%, specificity 84% area under the curve 0.817, p = 0.021). CONCLUSION The presence of high number of HRS and high subretinal fluid volume at the baseline negatively affect prognosis even in patient groups with early DEX shift.
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Affiliation(s)
- Mehmet Murat Uzel
- Department of Ophthalmoloy, Balıkesir University School of Medicine, Balıkesir, Turkey
| | - Eyyup Karahan
- Department of Ophthalmoloy, Balıkesir University School of Medicine, Balıkesir, Turkey
| | - Melek Koroglu Canli
- Department of Ophthalmoloy, Balıkesir University School of Medicine, Balıkesir, Turkey
| | - Cenap Guler
- Department of Ophthalmoloy, Balıkesir University School of Medicine, Balıkesir, Turkey
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Optical Coherence Tomography Predictors of Favorable Functional Response in Naïve Diabetic Macular Edema Eyes Treated with Dexamethasone Implants as a First-Line Agent. J Ophthalmol 2021; 2021:6639418. [PMID: 33833870 PMCID: PMC8012128 DOI: 10.1155/2021/6639418] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/17/2021] [Accepted: 03/17/2021] [Indexed: 12/11/2022] Open
Abstract
Purpose To evaluate efficacy and safety of intravitreal dexamethasone 0.7 mg implant in treatment-naïve DME patients and to assess the utility of OCT structural biomarkers as predictors of functional response after treatment. Methods Thirty-nine eyes of 39 diabetic patients with center involving DME were enrolled. Best-corrected visual acuity (BCVA) and SS-OCT (DRI SS-OCT Triton, Topcon, Japan) to evaluate central retinal thickness (CRT), serous retinal detachment (SRD), intraretinal cysts (IRC), number of hyper-reflective spots (HRS), integrity of the ellipsoid zone (EZ), disorganization of the inner retinal layers (DRIL), vitreomacular adhesion (VMA), vitreomacular traction (VMT), and posterior vitreous detachment (PVD) were evaluated at baseline and at 3, 6, and 12 months after treatment. Multiple logistic analysis was performed to evaluate the possible OCT biomarker as predictive factors for final visual acuity improvement at the end of treatment. Results At 12 months after treatment, the mean BCVA improved from 51.6 ± 17.5 to 56.9 ± 17.3 ETDRS letters (p=0.03). Furthermore, there were statistically significant changes in CRT, IRC, HRS, and SRD. Nineteen patients presented a >10-letters improvement in BCVA; the presence of SRD at baseline was a predictor of good functional treatment response at 12 months (OR 2.1; 95% C.I. 1.2–4.9; p=0.001) as well as the presence of EZ integrity preoperatively (OR 1.3; 95% C.I. 0.5–2.4; p=0.001) and the absence of vitreoretinal interface alteration (OR 1.1; 95% C.I. 0.3–2.3; p=0.02). No significant changes in the IOP and lens status were observed throughout the follow-up period. Conclusion This study empathized the importance of structural biomarkers as predictors of favorable response and confirmed the efficacy and safety of intravitreal dexamethasone implant in treatment-naïve DME patients showing a better functional response in the presence of SRD integrity of EZ and absence of vitreoretinal alterations.
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Cohen AF, van Meurs JC. Clinical ophtalmo-pharmacology. Looking ahead. Br J Clin Pharmacol 2021; 87:3483-3484. [PMID: 33751656 DOI: 10.1111/bcp.14776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 07/15/2020] [Accepted: 09/11/2020] [Indexed: 11/30/2022] Open
Affiliation(s)
- Adam F Cohen
- DDCD Consulting and Leiden University Medical Centre, CHDR InnoS, Leiden, The Netherlands
| | - Jan C van Meurs
- The Rotterdam Eye Hospital and ErasmusMC, Rotterdam, The Netherlands
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GRAding of functional and anatomical response to DExamethasone implant in patients with Diabetic Macular Edema: GRADE-DME Study. Sci Rep 2021; 11:4738. [PMID: 33637772 PMCID: PMC7910444 DOI: 10.1038/s41598-020-79288-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 11/30/2020] [Indexed: 01/19/2023] Open
Abstract
To analyze functional and anatomical response patterns to dexamethasone (DEX) implant in diabetic macular edema (DME), to describe proportion of responders and non-responders, and to propose a new DME grading system. Retrospective, multicenter, observational cohort study. Naïve and non-naïve DME patients were treated with DEX, with visual acuity (VA) ≥ 0.2 logMAR and central subfield thickness (CST) of ≥ 300 µm. Functional and anatomical responses were graded after 2 and 4 months, and categorized as early and stable improvement, early and progressive improvement, pendular response, delayed improvement, and persistent non-response. 417 eyes were included (175 treatment naïve eyes). Compared to non-naïve eyes, naïve eyes showed a very good functional response (VA gain ≥ 10 letters) more frequently after 2 and 4 months (56% and 57% [naïve] vs. 33% and 28% [non-naïve], p < 0.001). A VA gain < 5 letters (non-response) after 2 and 4 months was seen in 18% and 16% of naïve eyes, and in 49% and 53% of non-naïve eyes (p < 0.001). A lack of anatomical response was rare in both groups, but more frequently in non-naïve eyes (12% vs. 4%, p = 0.003). Functionally and anatomically, naïve eyes showed most frequently an early and stable improvement (functionally: 77/175 44%; anatomically: 123/175 eyes, 70%). Most non-naïve eyes experienced no significant improvement functionally (97/242 eyes, 40%), despite a mostly early and stable improvement anatomical response pattern (102/242 eyes, 42%). Functional but not anatomical response patterns were influenced by baseline VA. Naïve and non-naïve eyes show different functional and anatomical response patterns to DEX implant. Functional non-responders are rare in naïve eyes, whereas anatomical non-response is unusual in both groups.
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Veritti D, Sarao V, Soppelsa V, Lanzetta P. Managing Diabetic Macular Edema in Clinical Practice: Systematic Review and Meta-Analysis of Current Strategies and Treatment Options. Clin Ophthalmol 2021; 15:375-385. [PMID: 33551641 PMCID: PMC7856351 DOI: 10.2147/opth.s236423] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 01/22/2021] [Indexed: 12/15/2022] Open
Abstract
Purpose This meta-analysis aims to summarize 12-month best-corrected visual acuity (BCVA) outcomes in response to anti-vascular endothelial growth factor (VEGF) therapy and dexamethasone implant for the treatment of diabetic macular edema (DME) and to identify factors affecting treatment response using evidence generated from meta-regression. Methods A systematic review of electronic databases was conducted to identify randomized controlled trials (RCTs) and real-life/observational studies that reported 12-month changes in BCVA in patients with DME on anti-VEGF or dexamethasone implant treatment in monotherapy. Study factors that were analyzed are baseline patient characteristics, study type, drug employed, number of injections and 12-month change in BCVA. Data were pooled in a random-effects meta-analysis with BCVA change as the main outcome. Meta-regression was conducted to assess the impact of multiple covariates. Results One-hundred-five heterogeneous study populations (45,032 eyes) were identified and included in the analysis. The use of anti-VEGFs and dexamethasone implant induced an overall increase of +8.13 ETDRS letters in BCVA at 12 months of follow-up. Meta-regression provided evidence that mean BCVA change using anti-VEGFs was not statistically higher for RCTs (p=0.35) compared to observational studies. Dexamethasone implant showed a trend for better results in observational studies over RCTs. Populations following a fixed aflibercept regimen performed better than those following a reactive treatment regimen. Mean BCVA gain was higher in younger populations (p<0.001), with lower baseline BCVA (p<0.0001) and longer diabetes duration (p<0.0001), receiving a higher number of injections (p<0.0001). Conclusion Intravitreal therapy with anti-VEGFs or dexamethasone implant produces a significant improvement in BCVA at 12 months in patients with DME. Meta-regression identified the modifiable covariates that can be targeted in order to maximize functional results.
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Affiliation(s)
- Daniele Veritti
- Department of Medicine - Ophthalmology, University of Udine, Udine, Italy
| | - Valentina Sarao
- Department of Medicine - Ophthalmology, University of Udine, Udine, Italy.,Istituto Europeo di Microchirurgia Oculare (IEMO), Udine, Italy
| | - Valentina Soppelsa
- Department of Medicine - Ophthalmology, University of Udine, Udine, Italy
| | - Paolo Lanzetta
- Department of Medicine - Ophthalmology, University of Udine, Udine, Italy.,Istituto Europeo di Microchirurgia Oculare (IEMO), Udine, Italy
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Abstract
BACKGROUND Diabetic macular edema (DME) is secondary to leakage from diseased retinal capillaries with thickening of central retina, and is an important cause of poor central visual acuity in people with diabetic retinopathy. Intravitreal steroids have been used to reduce retinal thickness and improve vision in people with DME. OBJECTIVES To assess the effectiveness and safety of intravitreal steroid therapy compared with other treatments for DME. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase on 15 May, 2019. We also searched reference lists, Science Citation Index, conference proceedings, and relevant trial registers. We conducted a top up search on 21 October, 2020. SELECTION CRITERIA We included randomized controlled trials that evaluated any type of intravitreal steroids as monotherapy against any other intervention (e.g. observation, laser photocoagulation, anti-vascular endothelial growth factor (antiVEGF) for DME. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study eligibility and risk of bias and extracted data. Where appropriate, we performed meta-analyses. MAIN RESULTS We included 10 trials (4348 participants, 4505 eyes). These trials compared intravitreal steroid therapies versus other treatments, including intravitreal antiVEGF therapy, laser photocoagulation, and sham injection. Most trials had an overall unclear or high risk of bias. One trial (701 eyes ) compared intravitreal dexamethasone implant 0.7mg with sham. We found moderate-certainty evidence that dexamethasone leads to slightly more improvement of visual acuity than sham at 12 months (mean difference [MD] -0.08 logMAR, 95% confidence interval [CI] -0.12 to -0.05 logMAR). Regarding improvement of three or more lines of visual acuity, there was moderate-certainty evidence in favor of dexamethasone at 12 months, but the CI covered the null value (risk ratio (RR) 1.39, 95% CI 0.91 to 2.12). Regarding adverse events, dexamethasone increased by about four times the risk of cataract progression and the risk of using intraocular pressure (IOP)-lowering medications compared to sham (RR 3.89, 95% CI 2.75 to 5.50 and RR 4.54, 95% CI 3.19 to 6.46, respectively; moderate-certainty evidence); about 4 in 10 participants treated with dexamethasone needed IOP-lowering medications. Two trials (451 eyes) compared intravitreal dexamethasone implant 0.7mg with intravitreal antiVEGF (bevacizumab and ranibizumab). There was moderate-certainty evidence that visual acuity improved slightly less with dexamethasone compared with antiVEGF at 12 months (MD 0.07 logMAR, 95% CI 0.04 to 0.09 logMAR; 2 trials; 451 participants/eyes; I2 = 0%). The RR of gain of three or more lines of visual acuity was inconsistent between trials, with one trial finding no evidence of a difference between dexamethasone and bevacizumab at 12 months (RR 0.99, 95% CI 0.70 to 1.40; 1 trial; 88 eyes), and the other, larger trial finding the chances of vision gain were half with dexamethasone compared with ranibizumab (RR 0.50, 95% CI 0.32 to 0.79; 1 trial; 432 participants). The certainty of evidence was low. Cataract progression and the need for IOP-lowering medications increased more than 4 times with dexamethasone implant compared to antiVEGF (moderate-certainty evidence). One trial (560 eyes) compared intravitreal fluocinolone implant 0.19mg with sham. There was moderate-certainty evidence that visual acuity improved slightly more with fluocinolone at 12 months (MD -0.04 logMAR, 95% CI -0.06 to -0.01 logMAR). There was moderate-certainty evidence that an improvement in visual acuity of three or more lines was more common with fluocinolone than with sham at 12 months (RR 1.79, 95% CI 1.16 to 2.78). Fluocinolone also increased the risk of cataract progression (RR 1.63, 95% CI 1.35 to 1.97; participants = 335; moderate-certainty evidence), which occurred in about 8 in 10 participants, and the use of IOP-lowering medications (RR 2.72, 95% CI 1.87 to 3.98; participants = 558; moderate-certainty evidence), which were needed in 2 to 3 out of 10 participants. One small trial with 43 participants (69 eyes) compared intravitreal triamcinolone acetonide injection 4 mg with sham. There may be a benefit in visual acuity at 24 months (MD -0.11 logMAR, 95% CI -0.20 to -0.03 logMAR), but the certainty of evidence is low. Differences in adverse effects were poorly reported in this trial. Two trials (615 eyes) compared intravitreal triamcinolone acetonide injection 4mg with laser photocoagulation and reached discordant results. The smaller trial (31 eyes followed up to 9 months) found more visual acuity improvement with triamcinolone (MD -0.18 logMAR, 95% CI -0.29 to -0.07 logMAR), but a larger, multicenter trial (584 eyes, 12-month follow-up) found no evidence of a difference regarding change in visual acuity (MD 0.02 logMAR, 95% CI -0.03 to 0.07 logMAR) or gain of three or more lines of visual acuity (RR 0.85, 95% CI 0.55 to 1.30) (overall low-certainty evidence). Cataract progression was about three times more likely (RR 2.68, 95% CI 2.21 to 3.24; moderate-certainty evidence) and the use of IOP-lowering medications was about four times more likely (RR 3.92, 95% CI 2.59 to 5.96; participants = 627; studies = 2; I2 = 0%; moderate-certainty evidence) with triamcinolone. About 1 in 3 participants needed IOP-lowering medication. One small trial (30 eyes) compared intravitreal triamcinolone acetonide injection 4mg with intravitreal antiVEGF (bevacizumab or ranibizumab). Visual acuity may be worse with triamcinolone at 12 months (MD 0.18 logMAR, 95% CI 0.10 to 0.26 logMAR); the certainty of evidence is low. Adverse effects were poorly reported in this trial. Four trials reported data on pseudophakic participants, for whom cataract is not a concern. These trials found no decrease in visual acuity in the second treatment year due to cataract progression. AUTHORS' CONCLUSIONS Intravitreal steroids may improve vision in people with DME compared to sham or control. Effects were small, about one line of vision or less in most comparisons. More evidence is available for dexamethasone or fluocinolone implants when compared to sham, and the evidence is limited and inconsistent for the comparison of dexamethasone with antiVEGF treatment. Any benefits should be weighed against IOP elevation, the use of IOP-lowering medication and, in phakic patients, the progression of cataract. The need for glaucoma surgery is also increased, but remains rare.
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Affiliation(s)
- Thanitsara Rittiphairoj
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Tahreem A Mir
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Tianjing Li
- Department of Ophthalmology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
| | - Gianni Virgili
- Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
- Centre for Public Health, Queen's University Belfast, Belfast, UK
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Wallsh J, Luths C, Kil H, Gallemore R. Initial Ten Years of Experience with the Intravitreal Dexamethasone Implant: A Retrospective Chart Review. Clin Ophthalmol 2020; 14:3097-3108. [PMID: 33116361 PMCID: PMC7548337 DOI: 10.2147/opth.s264559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/07/2020] [Indexed: 11/23/2022] Open
Abstract
Purpose To evaluate the initial ten years of results from the intravitreal dexamethasone implant (DEX) in patients treated for retinal vein occlusion (RVO), diabetic macular edema (DME) or uveitis. Methods Retrospective chart review of patients receiving DEX since its FDA approval. Best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography, intraocular pressure and cataract status were collected. Baseline data were collected from the initial DEX and post-treatment data at the visit at least four weeks after the last DEX. Results In total, 315 eyes received 1216 DEX over 63.9±4.6 weeks. In the branch RVO (n=90), central RVO (n=59) and DME (n=62) cohorts, BCVA improved significantly (p<0.05). The uveitis (n=154) cohort did not have a significant change in BCVA, 0.62±0.04 to 0.61±0.04 logMAR (p=0.34). Younger patients, vitrectomized eyes, and eyes without a history of glaucoma were associated with significantly better BCVA outcomes in the uveitis cohort (p<0.05). Overall, CMT decreased significantly from 376.6±6.8 to 322.7±5.0 µm (p<0.05). Intraocular pressure increased significantly (p<0.001) and the percentage of patients requiring anti-glaucoma medications increased from 33.0% to 67.6%. Of phakic eyes, 58.8% (n=63) had cataract progression or underwent surgery with those who underwent surgery experiencing a significant improvement in BCVA (p<0.05). Conclusion Repeated DEX over extended follow-up offers significant anatomic benefits to all cohorts. Visual benefits are only seen in RVO, DME and select uveitis demographics.
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Affiliation(s)
- Josh Wallsh
- Albany Medical Center, Department of Ophthalmology, Albany, NY, USA
| | - Charlotte Luths
- Retina Macula Institute and Research Center, Torrance, CA, USA
| | - Haily Kil
- Retina Macula Institute and Research Center, Torrance, CA, USA
| | - Ron Gallemore
- Retina Macula Institute and Research Center, Torrance, CA, USA
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Petrachkov DV, Budzinskaya MV, Arzhukhanov DD. [The role of internal limiting membrane peeling in the treatment of diabetic macular edema]. Vestn Oftalmol 2020; 136:359-366. [PMID: 32880162 DOI: 10.17116/oftalma2020136042359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Analysis of the current understanding of the role of internal limiting membrane in the pathogenesis of diabetic macular edema and the feasibility of its surgical removal is based on data from domestic and international literature on pathogenesis, clinical manifestations, outcomes of multicenter studies of treatment and prognosis of this disease. The advantages and disadvantages of both peeling and preservation of the inner limiting membrane are described. The limitations and inconsistencies of data provided by the authors of each theory requires more complete functional studies in the pre- and postoperative periods, increasing the selection of patients, modifying the criteria for inclusion in groups, and microscopic examination of removed membranes. Thus, this issue requires further study due to the ambiguity of the conclusions and the lack of comparative data on the long-term prospects of each of the methods.
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Iovino C, Mastropasqua R, Lupidi M, Bacherini D, Pellegrini M, Bernabei F, Borrelli E, Sacconi R, Carnevali A, D’Aloisio R, Cerquaglia A, Finocchio L, Govetto A, Erba S, Triolo G, Di Zazzo A, Forlini M, Vagge A, Giannaccare G. 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:pharmaceutics12080703. [PMID: 32722556 PMCID: PMC7466091 DOI: 10.3390/pharmaceutics12080703] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 12/13/2022] Open
Abstract
Drug delivery into the vitreous chamber remains a great challenge in the pharmaceutical industry due to the complex anatomy and physiology of the eye. Intravitreal injection is the mainstream route of drug administration to the posterior segment of the eye. The purpose of this review is to assess the current literature about the widening use of the intravitreal 0.7 mg dexamethasone (Dex) implant, and to provide a comprehensive collection of all the ocular disorders that benefit from Dex administration. Although anti-vascular endothelial growth-factors (VEGFs) have been largely indicated as a first-choice level, the Dex implant represents an important treatment option, especially in selected cases, such as vitrectomized eyes or patients in whom anti-VEGF failed or are contraindicated. In this article, the safety profile as well as the list of the possible complications related to intravitreal Dex injection are also discussed.
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Affiliation(s)
- Claudio Iovino
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, 09124 Cagliari, Italy
- Correspondence: ; Tel.: +39-070-609-2319
| | - Rodolfo Mastropasqua
- Institute of Ophthalmology, University of Modena and Reggio Emilia, 41121 Modena, Italy;
| | - Marco Lupidi
- Department of Surgical and Biomedical Sciences, Section of Ophthalmology, University of Perugia, S. Maria della Misericordia Hospital, 06129 Perugia, Italy; (M.L.); (A.C.)
- Fondazione per la Macula Onlus, DINOMGI., University Eye Clinic, 16132 Genova, Italy
- Centre de l’Odéon, 113 Boulevard St Germain, 75006 Paris, France
| | - Daniela Bacherini
- Department of Neurosciences, Psychology, Drug Research and Child Health, Eye Clinic, University of Florence, AOU Careggi, 50139 Florence, Italy; (D.B.); (L.F.)
| | - Marco Pellegrini
- Ophthalmology Unit, S. Orsola-Malpighi University Hospital, University of Bologna, 40138 Bologna, Italy; (M.P.); (F.B.)
| | - Federico Bernabei
- Ophthalmology Unit, S. Orsola-Malpighi University Hospital, University of Bologna, 40138 Bologna, Italy; (M.P.); (F.B.)
| | - Enrico Borrelli
- Department of Ophthalmology, Hospital San Raffaele, University Vita Salute San Raffaele, 20132 Milan, Italy; (E.B.); (R.S.)
| | - Riccardo Sacconi
- Department of Ophthalmology, Hospital San Raffaele, University Vita Salute San Raffaele, 20132 Milan, Italy; (E.B.); (R.S.)
| | - Adriano Carnevali
- Department of Ophthalmology, University “Magna Graecia,” 88100 Catanzaro, Italy; (A.C.); (G.G.)
| | - Rossella D’Aloisio
- Department of Medicine and Science of Ageing, Ophthalmology Clinic, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy;
| | - Alessio Cerquaglia
- Department of Surgical and Biomedical Sciences, Section of Ophthalmology, University of Perugia, S. Maria della Misericordia Hospital, 06129 Perugia, Italy; (M.L.); (A.C.)
| | - Lucia Finocchio
- Department of Neurosciences, Psychology, Drug Research and Child Health, Eye Clinic, University of Florence, AOU Careggi, 50139 Florence, Italy; (D.B.); (L.F.)
- Moorfields Eye Hospital NHS Foundation Trust, London EC1V2PD, UK
| | - Andrea Govetto
- Fatebenefratelli-Oftalmico Hospital, ASST-Fatebenefratelli-Sacco, 63631 Milan, Italy; (A.G.); (S.E.); (G.T.)
- Bristol Eye Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol BS12LX, UK
| | - Stefano Erba
- Fatebenefratelli-Oftalmico Hospital, ASST-Fatebenefratelli-Sacco, 63631 Milan, Italy; (A.G.); (S.E.); (G.T.)
| | - Giacinto Triolo
- Fatebenefratelli-Oftalmico Hospital, ASST-Fatebenefratelli-Sacco, 63631 Milan, Italy; (A.G.); (S.E.); (G.T.)
| | - Antonio Di Zazzo
- Ophthalmology Complex Operative Unit, Campus Bio Medico University Hospital, 00128, Rome, Italy;
| | | | - Aldo Vagge
- University Eye Clinic, DINOGMI, Polyclinic Hospital San Martino IRCCS, 16132 Genoa, Italy;
| | - Giuseppe Giannaccare
- Department of Ophthalmology, University “Magna Graecia,” 88100 Catanzaro, Italy; (A.C.); (G.G.)
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