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Sharon Y, Shochat T, Rudman Y, Kushnir S, Zahavi A, Shimon I, Fleseriu M, Akirov A. Cushing's syndrome related to higher rates and earlier onset of cataract: A nationwide retrospective cohort study. Graefes Arch Clin Exp Ophthalmol 2025:10.1007/s00417-025-06752-6. [PMID: 39847049 DOI: 10.1007/s00417-025-06752-6] [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: 11/29/2024] [Revised: 01/15/2025] [Accepted: 01/15/2025] [Indexed: 01/24/2025] Open
Abstract
PURPOSE To investigate the risk of cataract in patients with Cushing's syndrome (CS) and evaluate whether disease onset occurs at an earlier age compared to general population. METHODS A nationwide retrospective matched-cohort study including individuals diagnosed with endogenous CS from 2000 to 2023. Patients with CS were matched in a 1:5 ratio with a control group individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was the incidence of cataract and cataract surgery. The Cox proportional hazards model, accounting for death without cataract as a competing risk, was employed to estimate hazard ratio. RESULTS The study cohort included 609 patients with CS, 65% women and 35% men, and 3018 controls. The average age at CS diagnosis was 48.1 ± 17 years. Follow-up duration was 14.6 years (IQR 9.8-20.2). The source of hypercortisolism was Cushing's disease (CD) in 259 (42.6%) and adrenal CS (aCS) in 206 patients (33.8%). After CS diagnosis, cataract was observed in 171 patients (28.1%), and 771 controls (25.5%). Patients with CS had a 34% higher risk of developing cataract compared to their matched controls (HR = 1.34, 95% CI 1.03-1.75, p = 0.03). Cataract developed earlier in patients with CS compared to controls, with a mean age of onset at 64.7 ± 9.7 versus 67.6 ± 8.4 years, respectively (p = 0.01). A total of 49 (8.05%) patients had undergone cataract surgery after a diagnosis of CS compared to 177 (5.86%) in the control group (p = 0.07). CONCLUSION Patients with endogenous CS have an increased likelihood of developing cataracts and they experienced onset at a younger age. Guidelines should include annual cataract monitoring for CS patients, beginning 3-5 years earlier than the current general recommendations.
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Affiliation(s)
- Yael Sharon
- Ophthalmology Department, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel.
- School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
| | - Tzipora Shochat
- Biostatistics Unit, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Yaron Rudman
- School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
| | - Shiri Kushnir
- Research Authority, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Alon Zahavi
- Ophthalmology Department, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
- School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
- Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva, Israel
| | - Ilan Shimon
- School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
| | - Maria Fleseriu
- Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
| | - Amit Akirov
- School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
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2
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Zhao J, Wang Y, Zhang Y, Guo X, Bao H, Tao Y. In Situ Crystallized Ceria-Vesicle Nanohybrid Therapeutic for Effective Treatment of Inflammatory Intraocular Disease. Adv Healthc Mater 2025; 14:e2402523. [PMID: 39440628 DOI: 10.1002/adhm.202402523] [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: 07/09/2024] [Revised: 09/21/2024] [Indexed: 10/25/2024]
Abstract
Posterior uveitis is a leading cause of vision impairment and blindness globally due to its detrimental effects on the choroid and retina. The condition is worsened by oxidative stress, which heightens inflammation and perpetuates a cycle of damage that current treatments only temporarily relieve. To address this, a novel treatment involving the in situ crystallization of ultrasmall cerium oxide nanoparticles (≈3 nm) on mesenchymal stem cell (MSC) extracellular vesicles (EVs) for the management of primed mycobacterial uveitis (PMU) is developed. This nanohybrid leverages the individual and synergistic effects of its components for a comprehensive therapeutic approach. The cerium oxide nanoparticles act as a nanozyme to reduce inflammation and scavenge excessive reactive oxygen species (ROS), while the MSC EVs, with their biocompatibility, modulate inflammatory cell infiltration and alleviate tissue damage. This synergistic system offers a promising new treatment strategy for ocular diseases characterized by oxidative stress and inflammation.
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Affiliation(s)
- Jiawei Zhao
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, P. R. China
| | - Yingjie Wang
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, P. R. China
| | - Yiquan Zhang
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, P. R. China
| | - Xinyu Guo
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, P. R. China
| | - Han Bao
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, P. R. China
| | - Yong Tao
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, P. R. China
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Bao H, Tian Y, Wang H, Ye T, Wang S, Zhao J, Qiu Y, Li J, Pan C, Ma G, Wei W, Tao Y. Exosome-loaded degradable polymeric microcapsules for the treatment of vitreoretinal diseases. Nat Biomed Eng 2024; 8:1436-1452. [PMID: 37872369 DOI: 10.1038/s41551-023-01112-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 09/26/2023] [Indexed: 10/25/2023]
Abstract
The therapeutic benefits of many cell types involve paracrine mechanisms. Inspired by the paracrine functions of exosomes and the sustained degradation properties of microcapsules, here we report the therapeutic benefits of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules with micrometric pores for the treatment of vitreoretinal diseases. On intravitreal injection in a mouse model of retinal ischaemia-reperfusion injury, microcapsules encapsulating mouse mesenchymal-stem-cell-derived exosomes settled in the inferior vitreous cavity, released exosomes for over one month as they underwent degradation and led to the restoration of retinal thickness to nearly that of the healthy retina. In mice and non-human primates with primed mycobacterial uveitis, intravitreally injected microcapsules loaded with exosomes from monkey regulatory T cells resulted in a substantial reduction in the levels of inflammatory cells. The exosome-encapsulating microcapsules, which can be lyophilised, may offer alternative treatment options for vitreoretinal diseases.
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Affiliation(s)
- Han Bao
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P. R. China
| | - Ying Tian
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P. R. China
| | - Haixin Wang
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China
| | - Tong Ye
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China
- School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China
| | - Shuang Wang
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China
| | - Jiawei Zhao
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China
| | - Yefeng Qiu
- Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing, P. R. China
| | - Jian Li
- Department of Ophthalmology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Chao Pan
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, P. R. China
| | - Guanghui Ma
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China.
- School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China.
| | - Wei Wei
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China.
- School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China.
| | - Yong Tao
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P. R. China.
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Kohli GM, Shenoy P, Halim D, Nigam S, Shetty S, Talwar D, Sen A. Safety and efficacy of suprachoroidal triamcinolone acetonide for the management of serous choroidal detachment prior to rhegmatogenous retinal detachment surgery: A Pilot study. Indian J Ophthalmol 2022; 70:1302-1306. [PMID: 35326041 PMCID: PMC9240553 DOI: 10.4103/ijo.ijo_1788_21] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Purpose To study the safety and efficacy of pre-operative suprachoroidal triamcinolone acetonide (SCTA) for achieving reduction/resolution of serous choroidal detachment (CD) associated with rhegmatogenous retinal detachment (RRD). Methods This was a prospective, noncomparative, interventional pilot study. All consecutive patients presenting with RD and coexisting CD underwent transconjunctival injection of SCTA before proceeding with vitrectomy/scleral buckle surgery. Sequential ultrasound B scans were performed for assessing the change in height of the CD. Results The mean age of the cohort was 53.8 ± 10.8 years (range: 39-72 years). The CD was present in a median of 3 quadrants; the cumulative mean CD height was 5.59 mm (range: 2.02-9.42 mm). Following SCTA, a successful response (>50% reduction) was seen in five eyes by day 3 and in two eyes by day 5. Three eyes failed to respond to SCTA and required surgical drainage before proceeding with vitrectomy. No intraprocedural injection-related complications were noted. A transient rise in the intraocular pressure (30 mmHg) was seen in one eye following vitrectomy and was managed successfully with topical antiglaucoma medications. Conclusion Suprachoroidal administration of triamcinolone appears to be a safe and effective technique to achieve CD resolution in eyes with RRD.
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Affiliation(s)
- Gaurav Mohan Kohli
- Department of Vitreo-retina and Uveitis, Shri Sadguru Seva Sangh Trust, Sadguru Netra Chikitsalaya, Chitrakoot, Madhya Pradesh; Department of Ophthalmology, Hind Institute of Medical Sciences, Sitapur, Uttar Pradesh, India
| | - Pratik Shenoy
- Department of Vitreo-retina and Uveitis, Shri Sadguru Seva Sangh Trust, Sadguru Netra Chikitsalaya, Chitrakoot, Madhya Pradesh, India
| | - Danish Halim
- Department of Vitreo-retina and Uveitis, Shri Sadguru Seva Sangh Trust, Sadguru Netra Chikitsalaya, Chitrakoot, Madhya Pradesh, India
| | - Saurabh Nigam
- Department of Vitreo-retina and Uveitis, Shri Sadguru Seva Sangh Trust, Sadguru Netra Chikitsalaya, Chitrakoot, Madhya Pradesh, India
| | - Sachin Shetty
- Department of Vitreo-retina and Uveitis, Shri Sadguru Seva Sangh Trust, Sadguru Netra Chikitsalaya, Chitrakoot, Madhya Pradesh, India
| | - Dinesh Talwar
- Department of Ophthalmology, Indraprastha Apollo Hospital and Center for Sight, New Delhi, India
| | - Alok Sen
- Department of Vitreo-retina and Uveitis, Shri Sadguru Seva Sangh Trust, Sadguru Netra Chikitsalaya, Chitrakoot, Madhya Pradesh, India
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Khan MS, Ravi PR, Mullapudi TVR. Dose identification of triamcinolone acetonide for noninvasive pre-corneal administration in the treatment of posterior uveitis using a rapid, sensitive HPLC method with photodiode-array detector. Biomed Chromatogr 2021; 36:e5264. [PMID: 34653273 DOI: 10.1002/bmc.5264] [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: 08/05/2021] [Revised: 10/03/2021] [Accepted: 10/05/2021] [Indexed: 11/07/2022]
Abstract
Triamcinolone acetonide (TAA) is the drug of choice in the management of ocular inflammations due to its anti-inflammatory and immuno-suppressant activity. Available marketed formulations (Triesence, Trivaris, Kenalog) are in the suspension form recommended to be administered via intravitreal injection, which has many major complications. In the present study, we have designed and evaluated Hydroxypropyl-β-cyclodextrin (HP-β-CD),) based conventional formulations of TAA (aqueous suspensions) with different dose strengths to identify the dose strength required for achieving the effective concentrations in vitreous humor following pre-corneal administration of the formulations. Ocular pharmacokinetic studies of conventional formulations of triamcinolone acetonide (TAA) with different dose strengths (1 mg/30µL, 2 mg/30µL, 4 mg/30µL) were performed to identify the dose strength required to produce effective concentrations of TAA in the aqueous and vitreous humor. A rapid, sensitive, selective, accurate and precise bioanalytical method utilizing a small sampling volume (<45 µL) was developed and validated for quantification of TAA in the samples obtained from the ocular pharmacokinetic studies. Aqueous suspensions of TAA with 20% HP-β-CD produced time course profiles in the aqueous humor at all the dose strengths. However, measurable concentrations and time course of TAA in vitreous humor were achieved only with 4 mg/30µL dose strength.
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Affiliation(s)
| | - Punna Rao Ravi
- Department of Pharmacy, BITS-Pilani Hyderabad Campus, Hyderabad, India
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Lee CH, Seo YS. Intraocular Pressure: Intravitreal Preservative-free Triamcinolone Injection in Diabetic Macular Edema and Branch Retinal Vein Occlusion. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2020. [DOI: 10.3341/jkos.2020.61.2.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Chan Ho Lee
- Department of Ophthalmology, Dankook University College of Medicine, Cheonan, Korea
| | - Young Seung Seo
- Department of Ophthalmology, Dankook University College of Medicine, Cheonan, Korea
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7
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Hostovsky A, Muni RH, Eng KT, Mulhall D, Leung C, Kertes PJ. Intraoperative Dexamethasone Intravitreal Implant (Ozurdex) in Vitrectomy Surgery for Epiretinal Membrane. Curr Eye Res 2019; 45:737-741. [PMID: 31765241 DOI: 10.1080/02713683.2019.1697454] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Objective: To study the effectiveness and safety of the intravitreal dexamethasone implant 0.7 mg (Ozurdex®) in vitrectomy surgery for epiretinal membrane.Methods: This is a prospective, multicenter, pilot study. Inclusion criteria included visually significant (<20/50) idiopathic epiretinal membrane. All patients underwent 23-gauge pars plana vitrectomy with membrane peeling and Ozurdex implant injection. The primary outcome measure was best corrected visual acuity (BCVA) change at 3 months. Secondary outcomes included BCVA at 6 months and changes in central retinal thickness (CRT). Intraocular (IOP) changes were monitored and cataract progression in phakic patients was documented.Results: 15 patients were enrolled in the study, 12 eyes of 12 patients were included in the analysis. Mean preoperative BCVA was 50.67 ETDRS letters and improved significantly to 63.67 (+12.91 letters, p = .008) at 3 months. Mean CRT improved from 548 to 409 microns (p = .002) at 3 months. The IOP showed mild elevation at months 1 and 2 and returned almost to baseline at month six. There were no complications related to the steroid implant injection procedure in an air-filled eye.Conclusions: Intra-operative injection of Ozurdex® at the conclusion of PPV can be done safely. The peak IOP and lowest CRT after 2 months strengthens the findings of prior studies demonstrating Ozurdex activity up to 3 months in vitrectomized eyes.
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Affiliation(s)
- Avner Hostovsky
- Department of Ophthalmology & Vision Sciences, The John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.,Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada
| | - Rajeev H Muni
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada.,Department of Ophthalmology, St.Michael's Hospital, Toronto, Canada
| | - Kenneth T Eng
- Department of Ophthalmology & Vision Sciences, The John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.,Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada
| | - Drew Mulhall
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada
| | - Christina Leung
- Department of Ophthalmology & Vision Sciences, The John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.,Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada
| | - Peter J Kertes
- Department of Ophthalmology & Vision Sciences, The John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.,Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada
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8
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Kumari N, Karmakar A, Ganesan SK. Targeting epigenetic modifications as a potential therapeutic option for diabetic retinopathy. J Cell Physiol 2019; 235:1933-1947. [PMID: 31531859 DOI: 10.1002/jcp.29180] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 08/26/2019] [Indexed: 12/20/2022]
Abstract
Diabetic retinopathy (DR) is the leading cause of visual impairment in adults of working age (20-65 years) in developed countries. The metabolic memory phenomena (persistent effect of a glycemic insult even after retrieved) associated with it has increased the risk of developing the complication even after the termination of the glycemic insult. Hence, the need for finding early diagnosis and treatment options has been of great concern. Epigenetic modifications which generally occur during the beginning stages of the disease are responsible for the metabolic memory effect. Therefore, the therapy based on the reversal of the associated epigenetic mechanism can bring new insight in the area of early diagnosis and treatment mechanism. This review discusses the diabetic retinopathy, its pathogenesis, current treatment options, need of finding novel treatment options, and different epigenetic alterations associated with DR. However, the main focus is emphasized on various epigenetic modifications particularly DNA methylation which are responsible for the initiation and progression of diabetic retinopathy and the use of different epigenetic inhibitors as a novel therapeutic option for DR.
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Affiliation(s)
- Nidhi Kumari
- Laboratory of Translational Genetics, Structural Biology & Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Aditi Karmakar
- Laboratory of Translational Genetics, Structural Biology & Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Senthil Kumar Ganesan
- Laboratory of Translational Genetics, Structural Biology & Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
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Liang X, Zhang Y, Wang JX, Wang LF, Huang WR, Tang X. Intravitreal ranibizumab injection at the end of vitrectomy for diabetic vitreous hemorrhage (Observational Study). Medicine (Baltimore) 2019; 98:e15735. [PMID: 31096535 PMCID: PMC6531093 DOI: 10.1097/md.0000000000015735] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
To evaluate the outcomes and complications of intravitreal injections of ranibizumab in patients during pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. This retrospective, observational, comparative study included 103 patients (103 eyes) who underwent pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. Sixty-six patients received an intravitreal injection of 0.05 mg (0.05 cc) of ranibizumab at the end of surgery. Main outcome measures were the occurrence of recurrent early vitreous hemorrhage, reoperation, intraocular pressure, best corrected visual acuity. Mean follow-up time was 6 months. The rate of rebleeding in the intravitreal ranibizumab (IVR) group was 6.1% (4 eyes), which is significantly lower than the control group (24.3%, 9 eyes, P < .01). The incidence of postoperative diabetic vitreous hemorrhage (PDVH) was significantly lower in the IVR group than the control group, OR=0.26, 95% CI= (0.06, 0.95). Visual acuity 6 months after operation was better in IVR group (P<.01) There was no difference in mean intraocular pressure between the 2 groups (P=.56). The present clinical study suggests that intravitreal injection of ranibizumab is effective in the prevention of postoperative diabetic vitreous hemorrhage in eyes undergoing pars plana vitrectomy for the treatment of diabetic vitreous hemorrhage.
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Affiliation(s)
- Xu Liang
- Clinical College of Ophthalmology, Tianjin Medical University
- Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, China
| | - Yue Zhang
- Clinical College of Ophthalmology, Tianjin Medical University
- Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, China
| | - Jia-Xing Wang
- Department of Ophthalmology, Emory University, Atlanta, GA
| | - Li-Fei Wang
- Hebei Provincial Key Laboratory of Ophthalmology, Hebei Provincial Eye Institute, Hebei Provincial Eye Hospital, Hebei, China
| | - Wan-Rong Huang
- Clinical College of Ophthalmology, Tianjin Medical University
- Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, China
| | - Xin Tang
- Clinical College of Ophthalmology, Tianjin Medical University
- Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, China
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10
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Anayol MA, Sekeroglu MA, Tirhis H, Gulpamuk B, Doguizi S, Yilmazbas P. Objective evaluation of lens clarity after the intravitreal injection of sustained-release dexamethasone implant. J Cataract Refract Surg 2018; 42:1477-1482. [PMID: 27839603 DOI: 10.1016/j.jcrs.2016.08.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Revised: 08/04/2016] [Accepted: 08/07/2016] [Indexed: 10/20/2022]
Abstract
PURPOSE To evaluate the lens densitometry values in eyes with macular edema secondary to retinal vein occlusion that were treated with intravitreal dexamethasone implants and to compare these data with those of fellow healthy control eyes. SETTING Ulucanlar Eye Training and Research Hospital, Ankara, Turkey. DESIGN Prospective case series. METHODS Patients with unilateral macular edema secondary to retinal vein occlusion who were to be treated with intravitreal dexamethasone implants were recruited. The lens densitometry values measured with Scheimpflug imaging before and 3 months after the injection were compared with those in fellow healthy eyes. RESULTS Thirty-seven patients (22 with branch retinal vein occlusion and 15 with central retinal vein occlusion) with a mean age of 61.5 years ± 11.4 (SD) (range 37 to 82 years) were included. The mean lens densitometry value at Pentacam densitometry zone 1 was significantly increased in the study eyes at 3 months compared with baseline values (baseline 9.44 ± 0.99; 3 months 9.68 ± 1.24; P = .015). At zones 2 and 3, the mean and maximum lens densitometry values in study eyes and lens thickness were similar at baseline and 3 months after injection (P > .05). The densitometry values in fellow healthy eyes were also similar at baseline and at 3 months. CONCLUSION The mean lens densitometry value at zone 1 significantly increased from baseline in the study eyes 3 months after the injection of the dexamethasone implant for the treatment of macular edema secondary to retinal vein occlusion. FINANCIAL DISCLOSURE None of the authors has a financial or proprietary interest in any material or method mentioned.
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Affiliation(s)
| | | | - Hakan Tirhis
- From the Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
| | - Bayram Gulpamuk
- From the Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
| | - Sibel Doguizi
- From the Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
| | - Pelin Yilmazbas
- From the Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
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11
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Jonas JB, Spandau UH, Kamppeter BA, Vossmerbaeumer U, Harder B. Follow-Up after Intravitreal Triamcinolone Acetonide for Diabetic Macular Edema. Eur J Ophthalmol 2018; 16:566-72. [PMID: 16952096 DOI: 10.1177/112067210601600411] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE To report on the follow-up of patients who received an intravitreal high-dosage injection of triamcinolone acetonide (IVTA) as treatment of diffuse diabetic macular edema. METHODS The clinical interventional case-series study included 109 eyes (90 patients) with diffuse diabetic macular edema who consecutively received an IVTA of about 20 mg. Mean follow-up was 11.2 +/- 6.2 months. RESULTS Visual acuity improved significantly (p<0.001) from 0.89 +/- 0.33 logMAR to a best minimum of 0.65 +/- 0.35 logMAR. An increase in best visual acuity by at least 1 Snellen line, 2 lines, and 3 lines was found in 91 (83%) eyes, 68 (62%) eyes, and 45 (41%) eyes, respectively. Differences in visual acuity between baseline and follow-up examinations were significant for measurements performed at 1 month (p<0.001), 2 months (p<0.001), 3 months (p<0.001), and at 6 months (p=0.001) after the injection. At 9 months after the injection, mean visual acuity regressed significantly so that visual acuity at 9 months (p=0.83) and at 12 months after the injection (p=0.58) compared with baseline values did not differ significantly. Forty-seven (43%) eyes developed a rise in intraocular pressure (pressure >21 mmHg) for 6 to 8 months after the injection. No other severe complications were detected. CONCLUSIONS The duration of a visual acuity increase and intraocular pressure rise after high-dosage IVTA in diffuse diabetic macular edema is about 6 to 8 months. Compared with data in the literature, the high-dosage IVTA may not have a markedly higher profile of side effects than low-dosage IVTA.
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Affiliation(s)
- J B Jonas
- Department of Ophthalmology, Faculty of Clinical Medicine Mannheim, Universitäts-Augenklinik, Ruprecht-Karls-University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
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12
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Trinh HM, Cholkar K, Joseph M, Yang X, Mitra AK. Clear, Aqueous Topical Drop of Triamcinolone Acetonide. AAPS PharmSciTech 2017; 18:2466-2478. [PMID: 28185211 DOI: 10.1208/s12249-017-0714-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Accepted: 01/05/2017] [Indexed: 01/04/2023] Open
Abstract
The objective of this study was to develop a clear aqueous mixed nanomicellar formulation (NMF) of triamcinolone acetonide (TA) with a combination of nonionic surfactant hydrogenated castor oil 60 (HCO-60) and octoxynol-40 (Oc-40). In order to delineate the effects of drug-polymer interactions on entrapment efficiency (EE), loading efficiency (LE), and critical micellar concentration (CMC), a design of experiment (DOE) was performed to optimize the formulation. In this study, full-factorial design has been used with HCO-60 and OC-40 as independent variables. All formulations were prepared following solvent evaporation and film rehydration method, characterized with size, polydispersity, shape, morphology, EE, LE, and CMC. A specific blend of HCO-60 and Oc-40 at a particular wt% ratio (5:1.5) produced highest drug EE, LE, and smallest CMC (0.0216 wt%). Solubility of TA in NMF improved 20 times relative to normal aqueous solubility. Qualitative 1H NMR studies confirmed the absence of free drug in the outer aqueous NMF medium. Moreover, TA-loaded NMF appeared to be highly stable and well tolerated on human corneal epithelial cells (HCEC) and human retinal pigment epithelial cells (D407 cells). Overall, these studies suggest that TA in NMF is safe and suitable for human topical ocular drop application.
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Blazaki S, Tsika C, Tzatzarakis M, Naoumidi E, Tsatsakis A, Tsatsanis C, Tsilimbaris MK. Pharmacokinetics and efficacy of intraocular flurbiprofen. Graefes Arch Clin Exp Ophthalmol 2017; 255:2375-2380. [DOI: 10.1007/s00417-017-3812-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 09/05/2017] [Accepted: 09/18/2017] [Indexed: 11/28/2022] Open
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Pachis K, Blazaki S, Tzatzarakis M, Klepetsanis P, Naoumidi E, Tsilimbaris M, Antimisiaris SG. Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation. Eur J Pharm Sci 2017; 109:324-333. [PMID: 28843864 DOI: 10.1016/j.ejps.2017.08.028] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 07/30/2017] [Accepted: 08/22/2017] [Indexed: 12/18/2022]
Abstract
A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated.
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Affiliation(s)
- K Pachis
- Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, University of Patras, Rio 26510, Patras, Greece
| | - S Blazaki
- Laboratory of Optics and Vision, Department of Medicine, University of Crete, Heraklion, Greece
| | - M Tzatzarakis
- Laboratory of Toxicology, Medical School, University of Crete, Heraklion, Greece
| | - P Klepetsanis
- Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, University of Patras, Rio 26510, Patras, Greece; Institute of Chemical Engineering, Foundation for Research and Technology Hellas, FORTH/ICE-HT, Platani 26504, Greece
| | - E Naoumidi
- Laboratory of Optics and Vision, Department of Medicine, University of Crete, Heraklion, Greece
| | - M Tsilimbaris
- Laboratory of Optics and Vision, Department of Medicine, University of Crete, Heraklion, Greece.
| | - S G Antimisiaris
- Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, University of Patras, Rio 26510, Patras, Greece; Institute of Chemical Engineering, Foundation for Research and Technology Hellas, FORTH/ICE-HT, Platani 26504, Greece.
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Efficacy of systemic diclofenac sodium on intravitreal concentration. Int Ophthalmol 2017; 38:99-104. [PMID: 28074420 DOI: 10.1007/s10792-016-0428-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Accepted: 12/26/2016] [Indexed: 10/20/2022]
Abstract
BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs), as an alternative, are replacing corticosteroids in ocular inflammatory diseases. Diclofenac has been used mainly topically, and recent focus has been on intravitreal delivery. Both of these methods have been shown to have complications in long-term application. PURPOSE To assess the efficacy of slow release oral diclofenac sodium on intravitreal concentration in experimental model of chemically injured eyes. METHODS In an experimental double-masked clinical trial, right eyes of 24 albino rabbits were chemically injured by 1 N NaOH. One hour after chemical injury, 10 cc suspension gavage containing 100 mg slow release diclofenac sodium was administered in all cases. 2, 4, 6, 12, 24, 48 h after gavage, vitreous samples were obtained in all cases. Intravitreal concentration of diclofenac sodium was evaluated in all samples using high-performance liquid chromatography (HPLC) method. RESULTS Intravitreal diclofenac levels by oral intake were enhanced by the inflammation in all the measurements. In inflamed eyes, diclofenac concentration was ten times more than control eye (2.658 ± 0.344 vs. 0.242 ± 0.0279 and 1.617 ± 0.527 vs. 0.148 ± 0.095; in 2 and 4 h, respectively). After 6 h, diclofenac concentration was statistically different, although it reduced below 1 μg/ml. CONCLUSION Diclofenac is delivered to the inflamed eye more than healthy eye. It seems that by oral diclofenac consumption, it is possible to make a significant intravitreal concentration.
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Corticosteroidi per via Intravitreale per il Trattamento Dell'edema Maculare: Revisione e Valutazione Della Qualità Dell'evidenza. GLOBAL & REGIONAL HEALTH TECHNOLOGY ASSESSMENT 2017. [DOI: 10.5301/grhta.5000251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Bolinger MT, Antonetti DA. Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy. Int J Mol Sci 2016; 17:E1498. [PMID: 27618014 PMCID: PMC5037775 DOI: 10.3390/ijms17091498] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/22/2016] [Accepted: 08/30/2016] [Indexed: 12/25/2022] Open
Abstract
Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin-kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies.
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Affiliation(s)
- Mark T Bolinger
- Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA.
| | - David A Antonetti
- Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA.
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Taskar P, Tatke A, Majumdar S. Advances in the use of prodrugs for drug delivery to the eye. Expert Opin Drug Deliv 2016; 14:49-63. [PMID: 27441817 DOI: 10.1080/17425247.2016.1208649] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Ocular drug delivery is presented with many challenges, taking into account the distinctive structure of the eye. The prodrug approach has been, and is being, employed to overcome such barriers for some drug molecules, utilizing a chemical modification approach rather than a formulation-based approach. A prodrug strategy involves modification of the active moiety into various derivatives in a fashion that imparts some advantage, such as membrane permeability, site specificity, transporter targeting and improved aqueous solubility, over the parent compound. Areas covered: The following review is a comprehensive summary of various novel methodologies and strategies reported over the past few years in the area of ocular drug delivery. Some of the strategies discussed involve polymer and lipid conjugation with the drug moiety to impart hydrophilicity or lipophilicity, or to target nutrient transporters by conjugation with transporter-specific moieties and retrometabolic drug design. Expert opinion: The application of prodrug strategies provides an option for enhancing drug penetration into the ocular tissues, and overall ocular bioavailability, with minimum disruption of the ocular diffusion barriers. Although success of the prodrug strategy is contingent on various factors, such as the chemical structure of the parent molecule, aqueous solubility and solution stability, capacity of targeted transporters and bioreversion characteristics, this approach has been successfully utilized, commercially and therapeutically, in several cases.
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Affiliation(s)
- Pranjal Taskar
- a Department of Pharmaceutics and Drug Delivery , University of Mississippi , University , MS , USA.,b Research Institute of Pharmaceutical Sciences , University of Mississippi , University , MS , USA
| | - Akshaya Tatke
- a Department of Pharmaceutics and Drug Delivery , University of Mississippi , University , MS , USA.,b Research Institute of Pharmaceutical Sciences , University of Mississippi , University , MS , USA
| | - Soumyajit Majumdar
- a Department of Pharmaceutics and Drug Delivery , University of Mississippi , University , MS , USA.,b Research Institute of Pharmaceutical Sciences , University of Mississippi , University , MS , USA
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Querques G, Darvizeh F, Querques L, Capuano V, Bandello F, Souied EH. Assessment of the Real-Life Usage of Intravitreal Dexamethasone Implant in the Treatment of Chronic Diabetic Macular Edema in France. J Ocul Pharmacol Ther 2016; 32:383-9. [PMID: 27285799 DOI: 10.1089/jop.2016.0010] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
PURPOSE Intravitreal steroids, including dexamethasone implant (Ozurdex(®)), are effective for the treatment of diabetic macular edema (DME). However, the dosing regimen for Ozurdex in DME is unclear, and thus, this study was designed to evaluate the dosing regimen for dexamethasone in real-life clinical practice. METHODS Results are presented from 3 studies based on a questionnaire that was sent out by e-mail to physicians; the monitoring of drugs dispensing over time through pharmacies; and the French Social Security database for 2011 and 2012. Data are presented as the average number of dexamethasone treatments per year and the time interval between injections. RESULTS Study 1 involved 111 ophthalmologists and assessed DME prescriptions. The number of injections per year and the time interval between 2 successive injections were measured as 2.3 and 4.8 months, respectively. In study 2, the survey incorporated 570 prescriptions from retail pharmacies; the mean follow-up period was 13.7 months, and 2.3 injections were administered per year with a time interval between injections of 5.2 months. In study 3, relating to the reimbursements by social security, 114 patients were initially identified and, among these, 15 patients were treated with Ozurdex. Over the course of a 25-month follow-up period, an average of 2.5 Ozurdex implants were injected per year with 4.7 months between injections. CONCLUSIONS The average number of dexamethasone implant injections was consistent between studies with an average of 2.4 injections per year and 4.9 months between treatments. This highlights the need for a study to evaluate the optimal treatment frequency in DME.
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Affiliation(s)
- Giuseppe Querques
- 1 Service d'Ophtalmologie, Centre Hospitalier Intercommunal de Créteil , Université Paris Est Creteil, France .,2 Department of Ophthalmology, IRCCS Ospedale San Raffaele, University Vita-Salute San Raffaele , Milan, Italy
| | - Fatemeh Darvizeh
- 2 Department of Ophthalmology, IRCCS Ospedale San Raffaele, University Vita-Salute San Raffaele , Milan, Italy
| | - Lea Querques
- 2 Department of Ophthalmology, IRCCS Ospedale San Raffaele, University Vita-Salute San Raffaele , Milan, Italy
| | - Vittorio Capuano
- 1 Service d'Ophtalmologie, Centre Hospitalier Intercommunal de Créteil , Université Paris Est Creteil, France
| | - Francesco Bandello
- 2 Department of Ophthalmology, IRCCS Ospedale San Raffaele, University Vita-Salute San Raffaele , Milan, Italy
| | - Eric H Souied
- 1 Service d'Ophtalmologie, Centre Hospitalier Intercommunal de Créteil , Université Paris Est Creteil, France
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Trinh HM, Joseph M, Cholkar K, Pal D, Mitra AK. Novel strategies for the treatment of diabetic macular edema. World J Pharmacol 2016; 5:1-14. [DOI: 10.5497/wjp.v5.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 12/19/2015] [Accepted: 01/07/2016] [Indexed: 02/06/2023] Open
Abstract
Macular edema such as diabetic macular edema (DME) and diabetic retinopathy are devastating back-of-the-eye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior ocular diseases are challenging to treat due to complex ocular physiology and barrier properties. Major ocular barriers are static (corneal epithelium, corneal stroma, and blood-aqueous barrier) and dynamic barriers (blood-retinal barrier, conjunctival blood flow, lymph flow, and tear drainage). Moreover, metabolic barriers impede posterior ocular drug delivery and treatment. To overcome such barriers and treat back-of-the-eye diseases, several strategies have been recently developed which include vitreal drainage, laser photocoagulation and treatment with biologics and/or small molecule drugs. In this article, we have provided an overview of several emerging novel strategies including nanotechnology based drug delivery approach for posterior ocular drug delivery and treatment with an emphasis on DME.
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Efficacy and safety of postvitrectomy intravitreal triamcinolone therapy for diabetic macular edema. Eur J Ophthalmol 2016; 26:485-90. [PMID: 26951531 DOI: 10.5301/ejo.5000768] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2016] [Indexed: 11/20/2022]
Abstract
PURPOSE After vitrectomy, diffusion and clearance rates of numerous drugs are increased, leading to a shorter intravitreal half-life. This raises doubts about the efficacy of intravitreal therapies, as retina specialists generally believe that a shorter half-life compromises the drugs' therapeutic effect. We conducted a study to evaluate the functional and anatomical effect of intravitreal triamcinolone acetonide therapy (IVTA) in previously vitrectomized eyes with diabetic macular edema (DME). METHODS In this retrospective, multicenter case series study including vitrectomized patients with DME who underwent IVTA injections, central macular thickness (CMT) measured with spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters were evaluated after each procedure. All relevant medical data were collected, including previous ophthalmologic treatments and comorbidities. RESULTS Twenty vitrectomized eyes of 20 patients, mean age 58.1 years (range 40-72 years), were enrolled in the study. All patients presented DME and received at least one IVTA injection. Mean time between pars plana vitrectomy and IVTA was 12.9 ± 8.7 months. Mean pretreatment and posttreatment CMT was 438.8 ± 90.8 μm and 301.2 ± 76.2 μm, respectively, a difference that reached statistical significance (p<0.001). Mean gain in BCVA letter score was 7.83 ± 14.9 letters after treatment (p = 0.039). Mean intraocular pressure was significantly increased after IVTA (17.2 ± 1.9 mm Hg at baseline vs 21.2 ± 4.59 mm Hg after IVTA, p = 0.002). CONCLUSIONS A positive anatomical and functional effect was observed in our cohort. Our results suggest that, despite prior vitrectomy, triamcinolone remains a valid therapeutic approach for eyes with persistent DME. Further prospective randomized studies with larger patient samples are needed to validate this conclusion.
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Hahn P, Yashkin AP, Sloan FA. Effect of Prior Anti-VEGF Injections on the Risk of Retained Lens Fragments and Endophthalmitis after Cataract Surgery in the Elderly. Ophthalmology 2016; 123:309-315. [PMID: 26278863 PMCID: PMC4724443 DOI: 10.1016/j.ophtha.2015.06.040] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 06/17/2015] [Accepted: 06/19/2015] [Indexed: 12/26/2022] Open
Abstract
PURPOSE To investigate the effect of prior intravitreal anti-vascular endothelial growth factor (VEGF) injections on surgical and postoperative complication rates associated with cataract surgery in a nationally representative longitudinal sample of elderly persons. DESIGN Retrospective, longitudinal cohort analysis. PARTICIPANTS A total of 203 643 Medicare beneficiaries who underwent cataract surgery from January 1, 2009, to December 31, 2013. METHODS By using the 5% sample of Medicare claims data, the study assessed risks of 3 adverse outcomes after receipt of cataract surgery for beneficiaries with a history of intravitreal injections. Risks of these outcomes in beneficiaries with a history of intravitreal injections relative to those without were calculated using the Cox proportional hazard model. MAIN OUTCOME MEASURES The primary outcome was the risk of subsequent removal of retained lens fragments (RLFs) within 28 days after cataract surgery. Secondary outcomes were a new diagnosis of acute (<40 days) or delayed-onset (40+ days) endophthalmitis and risk of a new primary open-angle glaucoma (POAG) diagnosis within 365 days after cataract surgery. RESULTS Prior intravitreal anti-VEGF injections were associated with a significantly increased risk of subsequent RLF removal within 28 days after cataract surgery (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.19-4.30). Prior injections were also associated with increased risk of both acute (HR, 2.29; 95% CI, 1.001-5.22) and delayed-onset endophthalmitis (HR, 3.65; 95% CI, 1.65-8.05). Prior injections were not a significant indicator of increased risk of a new POAG diagnosis. CONCLUSIONS A history of intravitreal injections may be a risk factor for cataract surgery-related intraoperative complications and endophthalmitis. Given the frequency of intravitreal injections and cataract surgery, increased preoperative assessment, additional intraoperative caution, and postoperative vigilance are recommended in patients with a history of intravitreal injections undergoing cataract extraction.
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Affiliation(s)
- Paul Hahn
- Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina
| | | | - Frank A Sloan
- Department of Economics, Duke University, Durham, North Carolina.
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Dodwell DG, Krimmel DA, de Fiebre CM. Sterile endophthalmitis rates and particle size analyses of different formulations of triamcinolone acetonide. Clin Ophthalmol 2015; 9:1033-40. [PMID: 26089635 PMCID: PMC4467755 DOI: 10.2147/opth.s82562] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
PURPOSE To evaluate the rate of sterile endophthalmitis (SE) following intravitreal injection of three different formulations of triamcinolone acetonide (TA) in a single physician practice and also to assess the mean diameter and concentration of particles of the two TA formulations currently available commercially in the USA. It was hypothesized that TA formulations with smaller particles and/or greater concentrations would have a higher incidence of SE. METHODS Single-site, interventional case series in which the medical records of 392 consecutive eyes receiving intravitreal TA as Triesence(®), Kenalog(®)-40, or preservative-free TA between September 2008 and October 2013 were retrospectively reviewed for the incidence of SE. Particle sizing of TA formulations was conducted by an independent commercial laboratory. RESULTS Five cases of SE were identified. The four cases of SE following Triesence(®) (4.6%) represented a rate significantly higher than the one case of SE following preservative-free TA (0.6%; P=0.049) and the 0% incidence rate of SE following Kenalog(®)-40 (P=0.0210). Triesence(®) had significantly smaller particles than Kenalog(®)-40 (P<0.0001). CONCLUSION The rate of SE was the highest with the formulation of TA that had the smallest particle size and highest particle load (number of particles injected). The lowest rate of SE was seen with Kenalog(®)-40, the only TA formulation that contained a benzyl alcohol preservative. The data do not support a principal causative role of benzyl alcohol in the development of TA-induced SE. Instead, the data support the particle theory of TA-induced SE; however, larger-scale, multicenter studies are needed to confirm and expand on these findings.
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Liu Q, He M, Shi H, Wang Q, Du Y, Liu J, Ren C, Xu D, Yu J. Efficacy and safety of different doses of a slow-release corticosteroid implant for macular edema: meta-analysis of randomized controlled trials. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:2527-35. [PMID: 26005329 PMCID: PMC4427600 DOI: 10.2147/dddt.s82929] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Background The purpose of this meta-analysis was to assess the efficacy and safety of intravitreal corticosteroid implants for macular edema. Methods A total of 3,586 patients from previously reported randomized controlled trials were included. The meta-analysis was performed using RevMan 5.2. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, employing random-effects or fixed-effects models according to between-study heterogeneity. The main outcome measures were the ORs for effects and safety of intravitreal corticosteroid implants. Results Four eligible studies were included. Compared with the sham group, the ORs for ≥15 letter improvement of visual acuity in the high-dose and low-dose groups were 1.89 (95% CI 1.33–2.69, P=0.0004) and 1.62 (95% CI 1.10–2.41, P=0.02), respectively. The weight mean differences in central retinal thickness increases were −75.46 (95% CI −90.29, −60.63, P<0.0001) and −46.47 (95% CI −92.08, −0.86, P=0.05), respectively. However, the ORs for increased intraocular pressure in both intervention groups were higher than in the sham group, and were 11.50 (95% CI 7.24–18.28, P<0.00001) and 10.30 (95% CI 6.49–16.36, P<0.00001), respectively. The incidence of cataract was 7.25 (95% CI 5.68–9.25, P<0.00001) and 3.56 (95% CI 1.28–9.96, P=0.02) in the two intervention groups, respectively. There was no significant difference between the intervention groups except for the incidence of cataract in which the OR was 1.59 (95% CI 1.28–1.97, P<0.001). Conclusion Intravitreal corticosteroid implants are effective in treating macular edema. However, the efficacy is not related to corticosteroid dose.
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Affiliation(s)
- Qingyu Liu
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China ; Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Mengmei He
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China ; Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Hui Shi
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China ; Department of First Clinical Medical College, Nanjing Medical University, Nanjing, People's Republic of China
| | - Qianyi Wang
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China ; Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Yaru Du
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China ; Department of First Clinical Medical College, Nanjing Medical University, Nanjing, People's Republic of China
| | - Junling Liu
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China ; Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Chengda Ren
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China ; Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Ding Xu
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China
| | - Jing Yu
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, People's Republic of China
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Abstract
Intravitreal injections for the treatment of retinal disorders and intraocular infection have become a common ophthalmic procedure, and injections of anti-vascular endothelial growth factor agents or steroids are frequently performed for the treatment of diabetic macular edema or other diabetic vascular pathology. Diabetic patients may be at higher risk of adverse events than non-diabetic individuals given frequent systemic co-morbidities, such as cardiovascular and renal disease, susceptibility to infection, and unique ocular pathology that includes fibrovascular proliferation. Fortunately, many associated complications, including endophthalmitis, are related to the injection procedure and can therefore be circumvented by careful attention to injection techniques. This review highlights the safety profile of intravitreal injections in patients with diabetes. Although diabetic patients may theoretically be at higher risk than non-diabetic patients for complications, a comprehensive review of the literature does not demonstrate substantial increased risk of intravitreal injections in patients with diabetes.
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Affiliation(s)
- Hasanain Shikari
- Beetham Eye Institute, Joslin Diabetes Center , Boston, Massachusetts , USA and
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Demir M, Dirim B, Acar Z, Sendul Y, Oba E. Comparison of the effects of intravitreal bevacizumab and triamcinolone acetonide in the treatment of macular edema secondary to central retinal vein occlusion. Indian J Ophthalmol 2015; 62:279-83. [PMID: 23571251 PMCID: PMC4061662 DOI: 10.4103/0301-4738.105769] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
AIM To compare the effects of intravitrealbevacizumab (IVB) and intravitreal triamcinolone acetonide (IVT) in the treatment of macular edema (ME) secondary to central retinal vein occlusion (CRVO). MATERIALS AND METHODS There were 20 patients treated with IVB (1.25 mg/0.05 mL) and 16 treated with IVT (4 mg/0.1 mL). The two groups were compared with regard to best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography (OCT), slit-lamp biomicroscopy and fundus fluorescein angiography results, intraocular pressure (IOP), numbers of injections, and adverse events. RESULTS The mean follow-up times in the IVB and IVT groups were 17.45±8.1 months (range: 8-33 months) and 19.94±10.59 months (range: 6-40 months), respectively (P = 0.431). Visual acuity increased and CMT decreased significantly within both groups, but no differences were observed between the groups (P = 0.718). The percentages of patients with increased IOP and iatrogenic cataracts were significantly higher in the IVT group than in the IVB group. CONCLUSIONS Treatment with IVB and IVT both resulted in significant improvement in visual acuity and a decrease in CMT in patients with ME secondary to non-ischemic CRVO, with no difference between the two treatments. The incidence of adverse events, however, was significantly greater in the IVT group than in the IVB group. IVB may be preferred over IVT for the treatment of ME in patients with non-ischemic CRVO.
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Affiliation(s)
- Mehmet Demir
- Department of Ophthalmology, Sisli Etfal Training and Research Hospital, Sisli, Istanbul, Turkey
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Degoumois A, Akesbi J, Laurens C, Rodallec FT, Adam R, Blumen-Ohana E, Laplace O, Virevialle C, Le Dû B, Guyader V, Nordmann JP. [Efficacy of intravitreal dexamethasone implants in macular edema excluding venous occlusions: results for a cohort of 80 patients]. J Fr Ophtalmol 2015; 38:126-33. [PMID: 25592383 DOI: 10.1016/j.jfo.2014.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Revised: 08/01/2014] [Accepted: 08/25/2014] [Indexed: 10/24/2022]
Abstract
INTRODUCTION The intravitreal dexamethasone implant has shown efficacy in the treatment of macular edema (ME) arising after retinal venous occlusions (central or branch), and in the treatment of non-infectious uveitis. The purpose of this study was to evaluate the efficacy of this implant in the treatment of other diffuse macular edemas with an inflammatory mechanism. MATERIALS AND METHODS We carried out a retrospective cohort study over 2 years: from January 2012 to December 2013, including all patients who received at least one injection of intravitreal dexamethasone implant, excluding venous occlusions and non-infectious uveitis. The primary study parameter was the progression of visual acuity. The study protocol had the approval of the institutional review board of the respective clinical ethics committees, and was conducted in accordance to the tenets of the Declaration of Helsinki. RESULTS Eighty patients were included. Eighty-eight percent of patients were pseudophakic. The indications for treatment were: diabetic ME when anti-VEGF were ineffective (53%), ME after retinal detachment (RD) (22%), ME of Irvine-Gass syndrome (16%), ME after endophthalmitis (4%), macular telangiectasia (4%), ME secondary to retinitis pigmentosa (1%). The mean ETDRS visual acuity was 53.7 letters prior to injection, improving to 62.3 letters after injection (P<0.001). The average gain in visual acuity was 6.7 letters [4.53;8.84] (P<0.001) in patients treated for diabetic ME, 9.6 letters [6.1;13.1] (P<0.001) in patients with ME after RD, and 15.2 letters [10.25;20.28] (P<0.001) for Irvine-Gass syndrome. The mean duration of efficiency was 4.6 months, with a median of 3.8 months. CONCLUSION The intravitreal dexamethasone implant appears to be an effective second-line treatment even in patients with diabetic ME after failure or in the case of contraindication of anti-VEGF. It is also effective and well tolerated in patients with ME after RD, as well as in patients with Irvine-Gass syndrome.
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Affiliation(s)
- A Degoumois
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France; Service d'ophtalmologie, centre hospitalier universitaire de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex, France.
| | - J Akesbi
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - C Laurens
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - F-T Rodallec
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - R Adam
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - E Blumen-Ohana
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - O Laplace
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - C Virevialle
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - B Le Dû
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - V Guyader
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
| | - J-P Nordmann
- Centre hospitalier national ophtalmologique des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France
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Cholkar K, Hariharan S, Gunda S, Mitra AK. Optimization of dexamethasone mixed nanomicellar formulation. AAPS PharmSciTech 2014; 15:1454-67. [PMID: 24980081 DOI: 10.1208/s12249-014-0159-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Accepted: 05/22/2014] [Indexed: 12/11/2022] Open
Abstract
The purpose of this study was to develop a clear aqueous mixed nanomicellar formulation (MNF) of dexamethasone utilizing both D-α-tocopherol polyethylene glycol-1000 succinate (Vit E TPGS) and octoxynol-40 (Oc-40). In this study, Vit E TPGS and Oc-40 are independent variables. Formulations were prepared following solvent evaporation method. A three level full-factorial design was applied to optimize the formulation based on entrapment efficiency, size, and polydispersity index (PDI). A specific blend of Vit E TPGS and Oc-40 at a particular wt% ratio (4.5:2.0) produced excellent drug entrapment, loading, small mixed nanomicellar size and narrow PDI. Solubility of DEX in MNF is improved by ~6.3-fold relative to normal aqueous solubility. Critical micellar concentration (CMC) for blend of polymers (4.5:2.0) was found to be lower (0.012 wt%) than the individual polymers (Vit E TPGS (0.025 wt%) and Oc-40 (0.107 wt%)). No significant effect on mixed nanomicellar size and PDI with one-factor or multi-factor interactions was observed. Qualitative (1)H NMR studies confirmed absence of free drug in the outer aqueous MNF medium. MNF appeared to be highly stable. Cytotoxicity studies on rabbit primary corneal epithelial cells did not indicate any toxicity suggesting MNF of dexamethasone is safe and suitable for human topical ocular drops after further in vivo evaluations.
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Corticosteroids for the Treatment of Diabetic Macular Edema. CURRENT OPHTHALMOLOGY REPORTS 2014. [DOI: 10.1007/s40135-014-0051-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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O'Day RF, Barthelmes D, Zhu M, Wong TY, McAllister IL, Arnold JJ, Gillies MC. Intraocular pressure rise is predictive of vision improvement after intravitreal triamcinolone acetonide for diabetic macular oedema: a retrospective analysis of data from a randomised controlled trial. BMC Ophthalmol 2014; 14:123. [PMID: 25335434 PMCID: PMC4223852 DOI: 10.1186/1471-2415-14-123] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2013] [Accepted: 09/25/2014] [Indexed: 01/27/2023] Open
Abstract
Background Intravitreal triamcinolone acetonide (IVTA) is an effective treatment for recalcitrant diabetic macular oedema (DMO). It has been shown to improve vision with benefits persisting up to five years. The most common initial side effect of IVTA treatment is rise in intraocular pressure, occurring in approximately 50% of patients within the first 6 months of treatment. We evaluated whether there is a correlation between the development of intraocular pressure rise and improvement in vision. Methods Analysis of individual data from 33 eyes of 33 participants treated with IVTA for DMO from a prospective, randomised, double-masked, placebo controlled trial. The degree of intraocular pressure (IOP) rise was correlated with improvement in best-corrected visual acuity (BCVA) at 1 and 6 months. Results The proportion of eyes gaining 5 or more logMAR letters was higher in eyes with greater IOP rise (p = 0.044). Better absolute improvement in BCVA at 6 months (p = 0.045) was also found in eyes with greater IOP rise. Regression analyses revealed a correlation between IOP rise of 10 or more mmHg and absolute BCVA improvement at 6 months (odds ratio 1.22, 95% confidence interval 1.01-1.48, p = 0.039), but not at 1 month. Conclusions IOP rise and vision improvement appear to be correlated following IVTA for DMO, suggesting that the mechanisms that cause both may be linked. Trial Registration Clinical trials.gov NCT00167518, September 5, 2005.
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Affiliation(s)
- Roderick F O'Day
- Clinical Ophthalmology & Eye Health, The University of Sydney, Sydney, Australia.
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Gerometta R, Kumar S, Shah S, Alvarez L, Candia O, Danias J. Reduction of steroid-induced intraocular pressure elevation in sheep by tissue plasminogen activator. Invest Ophthalmol Vis Sci 2013; 54:7903-9. [PMID: 24176900 DOI: 10.1167/iovs.13-12801] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To investigate whether tissue plasminogen activator (tPA) can prevent and/or reverse steroid-induced IOP elevation in an ovine model. METHODS Three animal groups were subjected to bilateral steroid-induced IOP elevation using thrice daily topical ocular prednisolone administration. In the first group (N = 8), one eye each of two sheep was injected intravitreally with 100 μg, 200 μg, 500 μg, or 1 mg human recombinant tPA, while contralateral eyes received vehicle. In the second group (N = 2), one eye was injected intravitreally with tPA (100 μg), while contralateral eyes received vehicle containing L-arginine. In the third group (N = 4), each animal received intravitreal tPA in one eye concurrently with initiation of bilateral steroid administration. IOP was monitored for the duration of the experiment. Tissues from eyes of the third group were used to determine relative gene expression. RESULTS In the first and second groups, IOP decreased by 9.7 (±2.8) and 9.7 (±1.6) mm Hg, respectively, 24 hours after tPA administration. In the third group, tPA-treated eyes did not develop IOP elevation with ΔIOP of 11.8 (±1.3) mm Hg 8 days later. In all tPA-treated eyes, IOP remained low until the end of the study. mRNA levels in the trabecular meshwork were decreased for plasminogen activator tissue (PLAT), increased for matrix-metalloproteinase 1 (MMP-1), and stable for plasminogen activator inhibitor 1 (PAI-1), MMP-2, MMP-9, and MMP-13 in tPA-treated eyes compared with contralateral controls. PAI-1 mRNA levels in ciliary processes also remained similar. CONCLUSIONS Recombinant human tPA is effective in both preventing and reversing steroid-induced IOP elevation in sheep. Tissue plasminogen activator may be useful as a therapeutic agent in steroid-induced glaucoma.
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Diakonis VF, Tsourdou A, Tzatzarakis MN, Tsika C, Charisis S, Naoumidi I, Plainis S, Tsilimbaris MK. Evaluation of Vitreous Clearance and Potential Retinal Toxicity of Intravitreal Lornoxicam (Xefo). J Ocul Pharmacol Ther 2013; 29:627-32. [DOI: 10.1089/jop.2012.0194] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Vasilios F. Diakonis
- Institute of Vision and Optics (IVO), University of Crete, Heraklion, Greece
- Department of Ophthalmology, University of Crete, Heraklion, Greece
| | - Antigoni Tsourdou
- Institute of Vision and Optics (IVO), University of Crete, Heraklion, Greece
| | | | - Chrysanthi Tsika
- Department of Ophthalmology, University of Crete, Heraklion, Greece
| | | | - Irini Naoumidi
- Institute of Vision and Optics (IVO), University of Crete, Heraklion, Greece
| | - Sotiris Plainis
- Institute of Vision and Optics (IVO), University of Crete, Heraklion, Greece
| | - Miltiadis K. Tsilimbaris
- Institute of Vision and Optics (IVO), University of Crete, Heraklion, Greece
- Department of Ophthalmology, University of Crete, Heraklion, Greece
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O'Day R, Barthelmes D, Zhu M, Wong TY, McAllister IL, Arnold JJ, Gillies MC. Baseline central macular thickness predicts the need for retreatment with intravitreal triamcinolone plus laser photocoagulation for diabetic macular edema. Clin Ophthalmol 2013; 7:1565-70. [PMID: 23946643 PMCID: PMC3739543 DOI: 10.2147/opth.s47424] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Purpose To identify baseline characteristics that predict the number of treatments with intravitreal triamcinolone acetonide (IVTA) plus laser photocoagulation needed to treat diabetic macular edema over a 2-year period. Methods Individual data from 42 eyes of 42 participants treated with IVTA plus laser photocoagulation for diabetic macular edema during a prospective, randomized, double-masked, placebo-controlled trial were used for this post hoc analysis. Baseline characteristics – age, gender, best-corrected visual acuity, glycosylated hemoglobin, phakic status, intraocular pressure, and central macular thickness (CMT) – were correlated with the number of IVTA plus laser treatments received during the 2 years of this study. Results The median number of treatments received over the 2-year period was 2.5 (interquartile range 1.0–3.0), with 21 (50%) eyes needing three or more treatments. Eyes that received more IVTA plus laser treatments had a higher mean baseline CMT and eyes with a higher baseline CMT were more likely to receive three or more treatments (odds ratio 5.13, 95% confidence interval 1.75–15.04, P=0.003 per 100 μm increase in CMT). No significant relationship was found between other baseline characteristics and the number of IVTA plus laser treatments received. Conclusion Higher baseline CMT was strongly linked with receiving more IVTA plus laser treatments. These patients may be at higher risk of developing dose-dependent steroid-related adverse events, cataract progression, and intraocular pressure rise.
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Affiliation(s)
- Roderick O'Day
- Clinical Ophthalmology and Eye Health, The University of Sydney, Sydney, NSW, Australia
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Intraocular Pressure Monitoring Post Intravitreal Steroids: A Systematic Review. Surv Ophthalmol 2013; 58:291-310. [DOI: 10.1016/j.survophthal.2012.08.003] [Citation(s) in RCA: 122] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2012] [Revised: 08/04/2012] [Accepted: 08/07/2012] [Indexed: 12/29/2022]
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Lee Y, Kang S, Park YH. Posterior subtenon triamcinolone acetonide in gas-filled eyes as an adjunctive treatment for complicated proliferative diabetic retinopathy. KOREAN JOURNAL OF OPHTHALMOLOGY 2013; 27:28-33. [PMID: 23372376 PMCID: PMC3550308 DOI: 10.3341/kjo.2013.27.1.28] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2011] [Accepted: 04/06/2012] [Indexed: 11/23/2022] Open
Abstract
PURPOSE To evaluate the effect of adjunctive subtenon injection of triamcinolone acetonide (TA) in gas-filled eyes after vitrectomy for complicated proliferative diabetic retinopathy (PDR). METHODS This nonrandomized comparative study included 27 patients (27 eyes) who underwent pars plana vitrectomy and gas tamponade for treatment of PDR with tractional or combined tractional-rhegmatogenous retinal detachment and who received subtenon injection of TA (40 mg) at the end of surgery. The study group was compared with the control group (29 eyes), which was matched with the study group for preoperative and intraoperative parameters, but underwent pars plana vitrectomy and gas tamponade without a subtenon injection of TA. RESULTS Retinal reattachments without reoperation were achieved in 25 eyes (92.6%) and 26 eyes (89.7%) at 6 months (p = 1.000) in the study and control groups, respectively. The study group and the control group did not differ significantly in the frequency of postoperative proliferative vitreoretinopathy, retinal redetachment rate, reoperation rate, macular pucker formation, postoperative vitreous hemorrhage, gain in visual acuity, intraocular pressure, and intraocular inflammation (p > 0.05). CONCLUSIONS The clinical results of pars plana vitrectomy for complicated PDR are not improved significantly by an adjunctive subtenon TA injection in gas-filled eyes.
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Affiliation(s)
- Yongeun Lee
- Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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Han HC, Bang JW, Yum JH, Kim JH, Lee DH, Lee JH. A Case of Acute Endophthalmitis Following a Dexamethasone Intravitreal Implant. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2013. [DOI: 10.3341/jkos.2013.54.12.1939] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Hyun Cheol Han
- Department of Ophthalmology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Jong Wook Bang
- Department of Ophthalmology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Jung Hoon Yum
- Department of Ophthalmology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Jin Hyoung Kim
- Department of Ophthalmology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Do Hyung Lee
- Department of Ophthalmology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Jong Hyun Lee
- Department of Ophthalmology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
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Sonmez K, Ozturk F. Complications of intravitreal triamcinolone acetonide for macular edema and predictive factors for intraocular pressure elevation. Int J Ophthalmol 2012; 5:719-25. [PMID: 23275907 DOI: 10.3980/j.issn.2222-3959.2012.06.13] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2012] [Accepted: 11/10/2012] [Indexed: 12/25/2022] Open
Abstract
AIM To investigate the complications of intravitreal triamcinolone acetonide (IVTA) for the treatment of macular edema, and to determine the risk factors for intraocular pressure (IOP) elevation. METHODS Charts of patients with macular edema secondary to branch retinal vein occlusion (BRVO), diabetic retinopathy and uveitis who had received IVTA injections were reviewed to document its complications. IOP elevation was defined as a pressure of ≥24mmHg at some point during follow-up. Multivariate logistic regression analysis was performed to characterize baseline risk factors for this elevation. RESULTS The study included 111 eyes of 65 female and 46 male patients with a mean follow-up of (11.6±5.1) months. Of the 111 eyes, 52 (46.8%) had macular edema secondary to BRVO, 44 (39.6%) had clinically significant diabetic macular edema (CSDME) and 15 (13.5%) had non-infectious uveitis with macular edema. IOP was recorded ≥ 24mmHg in 38 eyes (34.2%) during the follow-up. Higher baseline IOP (P=0.022), younger age (P=0.003), and male gender (P=0.014) were significant risk factors for IOP elevation after IVTA injection. Eyes with prior vitrectomy were less likely to have IOP elevation (P=0.054). Two eyes (5.2% of eyes with increased IOP) underwent trabeculectomy, and 9 eyes (16.3% of the phakic eyes) necessitated cataract surgery. Other complications included branch vein occlusion (1.8%), sterile endophthalmitis (0.9%) and pseudohypopyon (0.9%). CONCLUSION IVTA has side effects with IOP elevation and cataract formation being the two most common. A subset of patients is more prone to developing increased IOP following IVTA, namely, younger male patients with higher baseline IOP.
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Affiliation(s)
- Kenan Sonmez
- Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
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Abstract
Diabetic retinopathy is the leading cause of blindness in working age individuals in developed countries. Most cases of diabetes related vision loss result from breakdown of the blood-retinal barrier with resultant diabetic macular edema (DME). For over 30 years, laser photocoagulation has been the standard therapy for DME, but most eyes do not experience significant improvements in visual acuity. Intravitreal injections of drugs that inhibit the action of vascular endothelial growth factor (VEGF) lead to gains in vision, but can be expensive and need to be repeated frequently. In addition to VEGF-mediated breakdown of the blood-retinal barrier, recent evidence suggests that inflammation plays an important role in the development of DME. Recognizing this, physicians have injected steroids into the vitreous and developers have created sustained release implants. Intravitreal injections of triamcinolone acetonide lead to rapid resolution of macular edema and significant short-term improvements in visual acuity, but unfortunately, visual acuities diminish when treatment is continued through 2 years. However, intravitreal triamcinolone remains an attractive treatment option for eyes that are pseudophakic, scheduled to undergo cataract surgery, resistant to laser photocoagulation, or require urgent panretinal photocoagulation for proliferative retinopathy. In controlled trials, intraocular implants that slowly release dexamethasone and fluocinolone show promise in reducing macular edema and improving visual acuity. The high incidences of drug related cataracts and glaucoma, however, require that corticosteroids be used cautiously and that patients be selected carefully. The increasing number of patients with DME, the burgeoning cost of medical care and the continuing development of intravitreal steroids suggest that the use of these agents will likely increase in coming years.
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Pickrell A, Harris A, Ngo S, Amireskandari A, Stewart E, Siesky B. Delivery of intraocular triamcinolone acetonide in the treatment of macular edema. Pharmaceutics 2012; 4:230-42. [PMID: 24300190 PMCID: PMC3834899 DOI: 10.3390/pharmaceutics4010230] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2012] [Revised: 02/28/2012] [Accepted: 03/09/2012] [Indexed: 12/02/2022] Open
Abstract
Macular edema (ME) is one of the eventual outcomes of various intraocular and systemic pathologies. The pathogenesis for ME is not yet entirely understood; however, some of the common risk factors for its development have been identified. While this investigation will not discuss the numerous etiologies of ME in detail, it appraises the two most widely studied delivery modalities of intraocular corticosteroids in the treatment of ME—intravitreal injection (IVI) and sub-Tenon’s infusion (STI). A thorough review of the medical literature was conducted to identify the efficacy and safety of IVI and STI, specifically for the administration of triamcinolone acetonide (TA), in the setting of ME in an attempt to elucidate a preferred steroid delivery modality for treatment of ME.
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Affiliation(s)
- Aaron Pickrell
- Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, 1160 W. Michigan Street, Room 205Q, Indianapolis, IN 46202, USA.
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Prieto E, Puente B, Uixera A, Garcia de Jalon J, Perez S, Pablo L, Irache J, Garcia M, Bregante M. Gantrez AN Nanoparticles for Ocular Delivery of Memantine: In vitro Release Evaluation in Albino Rabbits. Ophthalmic Res 2012; 48:109-17. [DOI: 10.1159/000337136] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2011] [Accepted: 01/20/2012] [Indexed: 11/19/2022]
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Kang HK, Chin HS. Complications after Intravitreal Triamcinolone Acetonide Injection: Incidence and Risk Factors. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2012. [DOI: 10.3341/jkos.2012.53.1.76] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Haeng Ku Kang
- Department of Ophthalmology, Inha University School of Medicine, Incheon, Korea
| | - Hee Seung Chin
- Department of Ophthalmology, Inha University School of Medicine, Incheon, Korea
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Veritti D, Di Giulio A, Sarao V, Lanzetta P. Drug safety evaluation of intravitreal triamcinolone acetonide. Expert Opin Drug Saf 2011; 11:331-40. [PMID: 22066820 DOI: 10.1517/14740338.2012.635141] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Triamcinolone acetonide (TA) is a steroidal drug that has been widely administered intravitreally for retinal and choroidal conditions. Safety of steroidal products for intraocular use is essential because of their risk of ocular adverse events. This review comprehensively discusses the safety of intravitreal administration of TA. AREAS COVERED This paper analyzes the mechanisms of action and key pharmacokinetic attributes and provides a discussion of the main clinical trials investigating clinical applications of intravitreal TA. The safety of intravitreal TA is evaluated through a search of the Medline database from 1980 to 2011. The most relevant literature on the safety of intravitreal TA is also discussed. EXPERT OPINION The complications of intravitreal TA therapy include secondary ocular hypertension in about 20 - 40% of eyes, steroid-induced cataract in about 15 - 20% of cases and postinjection infectious endophthalmitis and pseudoendophthalmitis in less than 1%. TA is an effective drug for various retinal and choroidal diseases when delivered intravitreally. It may imply an off-label use and it may be associated with ocular adverse events. Intravitreal TA is not associated with significant systemic safety risks.
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Affiliation(s)
- Daniele Veritti
- University of Udine, Department of Ophthalmology, P.le S. Maria della Misericordia, 33100 Udine, Italy
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Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial. Ophthalmology 2011; 118:1580-7. [PMID: 21813090 DOI: 10.1016/j.ophtha.2011.02.048] [Citation(s) in RCA: 151] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2010] [Revised: 02/23/2011] [Accepted: 02/28/2011] [Indexed: 11/21/2022] Open
Abstract
PURPOSE We studied the 3-year efficacy and safety results of a 4-year study evaluating fluocinolone acetonide (FA) intravitreal implants in eyes with persistent or recurrent diabetic macular edema (DME). DESIGN Prospective, evaluator-masked, controlled, multicenter clinical trial. PARTICIPANTS We included 196 eyes with refractory DME. METHODS Patients were randomized 2:1 to receive 0.59-mg FA implant (n = 127) or standard of care (SOC additional laser or observation; n = 69). The implant was inserted through a pars plana incision. Visits were scheduled on day 2, weeks 1, 3, 6, 12, and 26, and thereafter every 13 weeks through 3 years postimplantation. MAIN OUTCOME MEASURES The primary efficacy outcome was ≥15-letter improvement in visual acuity (VA) at 6 months. Secondary outcomes included resolution of macular retinal thickening and Diabetic Retinopathy Severity Score (DRSS). Safety measures included incidence of adverse events (AEs). RESULTS Overall, VA improved ≥3 lines in 16.8% of implanted eyes at 6 months (P=0.0012; SOC, 1.4%); in 16.4% at 1 year (P=0.1191; SOC, 8.1%); in 31.8% at 2 years (P=0.0016; SOC, 9.3%); and in 31.1% at 3 years (P=0.1566; SOC, 20.0%). The number of implanted eyes with no evidence of retinal thickening at the center of the macula was higher than SOC eyes at 6 months (P<0.0001), 1 year (P<0.0001; 72% vs 22%), 2 years (P=0.016), and 3 years (P=0.861). A higher rate of improvement and lower rate of decline in DRSS occurred in the implanted group versus the SOC group at 6 months (P=0.0006), 1 year (P=0.0016), 2 years (P=0.012), and 3 years (P=0.0207). Intraocular pressure (IOP) ≥30 mmHg was recorded in 61.4% of implanted eyes (SOC, 5.8%) at any time and 33.8% required surgery for ocular hypertension by 4 years. Of implanted phakic eyes, 91% (SOC, 20%) had cataract extraction by 4 years. CONCLUSIONS The FA intravitreal implant met the primary and secondary outcomes, with significantly improved VA and DRSS and reduced DME. The most common AEs included cataract progression and elevated IOP. The 0.59-mg FA intravitreal implant may be an effective treatment for eyes with persistent or recurrent DME. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.
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Sharma A, Pirouzmanesh A, Patil J, Estrago-Franco MF, Zacharias LC, Pirouzmanesh A, Andley UP, Kenney MC, Kuppermann BD. Evaluation of the toxicity of triamcinolone acetonide and dexamethasone sodium phosphate on human lens epithelial cells (HLE B-3). J Ocul Pharmacol Ther 2011; 27:265-71. [PMID: 21574867 DOI: 10.1089/jop.2010.0120] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
PURPOSE The purpose of this study was to compare the in vitro effects of triamcinolone acetonide (TA) and dexamethasone sodium phosphate (DEX) on human lens epithelial cells (HLE B-3). METHODS HLE B-3 cells were exposed for 24 h to commercially available TA (c-TA) and dimethylsulfoxide-solubilized TA (s-TA). The cells were treated with 1,000 (clinical dose), 750, 500, 200, and 100 μg/mL concentrations of c-TA, s-TA, and supernatant for 24 h. The cells were also treated with DEX at 2, 1, 0.5, 0.2, 0.1 (clinical dose), and 0.05 mg/mL. Cell viability, caspase-3/7 activity, and DNA fragmentation analyses were performed. RESULTS The mean cell viabilities of HLE B-3 after exposure to c-TA at 1,000, 750, 500, 200, and 100 μg/mL were significantly reduced compared with control untreated cells. The s-TA also significantly reduced cell viability at 1,000, 750, and 500 μg/mL compared with dimethylsulfoxide control. The supernatant did not reduce cell viability. Caspase-3/7 activity significantly increased after treatment with c-TA and s-TA. DNA laddering revealed bands at 200 bp intervals with both c-TA at≥100 μg/mL and s-TA at ≥500 μg/mL. The cell viabilities of HLE B-3 after 24 h exposure to DEX were significantly reduced at 2 and 1 mg/mL but not at lower concentrations tested. Caspase-3/7 activities in HLE B-3 cells were not increased significantly after treatment with DEX at any dose tested. DNA laddering did not reveal any band at any dose tested. CONCLUSION This study showed that TA at its clinical dose (1,000 μg/mL) in both commercial preparation and solubilized forms decrease HLE B-3 cell viability through an apoptotic pathway. DEX at its clinical dose (0.1 mg/mL) does not decrease cell viability or cause any increase of caspase-3/7 activity. This study suggests that for long-term sustained-release devices, DEX may be less damaging to human lens cells than TA.
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Affiliation(s)
- Ashish Sharma
- Gavin Herbert Eye Institute Department of Ophthalmology, School of Medicine, University of California at Irvine, Irvine, California 92697, USA
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Wiley LA, Rajagopal R, Dattilo LK, Beebe DC. The tumor suppressor gene Trp53 protects the mouse lens against posterior subcapsular cataracts and the BMP receptor Acvr1 acts as a tumor suppressor in the lens. Dis Model Mech 2011; 4:484-95. [PMID: 21504908 PMCID: PMC3124053 DOI: 10.1242/dmm.006593] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
We previously found that lenses lacking the Acvr1 gene, which encodes a bone morphogenetic protein (BMP) receptor, had abnormal proliferation and cell death in epithelial and cortical fiber cells. We tested whether the tumor suppressor protein p53 (encoded by Trp53) affected this phenotype. Acvr1 conditional knockout (Acvr1CKO) mouse fiber cells had increased numbers of nuclei that stained for p53 phosphorylated on serine 15, an indicator of p53 stabilization and activation. Deletion of Trp53 rescued the Acvr1CKO cell death phenotype in embryos and reduced Acvr1-dependent apoptosis in postnatal lenses. However, deletion of Trp53 alone increased the number of fiber cells that failed to withdraw from the cell cycle. Trp53CKO and Acvr1;Trp53DCKO (double conditional knockout), but not Acvr1CKO, lenses developed abnormal collections of cells at the posterior of the lens that resembled posterior subcapsular cataracts. Cells from human posterior subcapsular cataracts had morphological and molecular characteristics similar to the cells at the posterior of mouse lenses lacking Trp53. In Trp53CKO lenses, cells in the posterior plaques did not proliferate but, in Acvr1;Trp53DCKO lenses, many cells in the posterior plaques continued to proliferate, eventually forming vascularized tumor-like masses at the posterior of the lens. We conclude that p53 protects the lens against posterior subcapsular cataract formation by suppressing the proliferation of fiber cells and promoting the death of any fiber cells that enter the cell cycle. Acvr1 acts as a tumor suppressor in the lens. Enhancing p53 function in the lens could contribute to the prevention of steroid- and radiation-induced posterior subcapsular cataracts.
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Affiliation(s)
- Luke A Wiley
- Department of Ophthalmology and Visual Sciences, Washington University, Saint Louis, MO 63110, USA
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Margalit E, Boysen JL, Zastrocky JP, Katz A. Use of intraocular ketorolac tromethamine for the treatment of chronic cystoid macular edema. Can J Ophthalmol 2010; 45:409-10. [DOI: 10.3129/i09-281] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
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Gerometta R, Spiga MG, Borrás T, Candia OA. Treatment of sheep steroid-induced ocular hypertension with a glucocorticoid-inducible MMP1 gene therapy virus. Invest Ophthalmol Vis Sci 2010; 51:3042-8. [PMID: 20089869 PMCID: PMC2891463 DOI: 10.1167/iovs.09-4920] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2009] [Revised: 01/12/2010] [Accepted: 01/13/2010] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To investigate whether intracameral injection of the adenovirus vector AdhGRE.MMP1 would reduce or prevent elevated intraocular pressure (IOP) induced by corticosteroids in living animals. METHODS Glucocorticoid-inducible adenovirus vectors carrying wild-type or mutant forms of human metalloproteinase 1 (MMP1 and mutMMP1) cDNAs were generated. An adenovirus carrying no gene (Ad5.CMV.Null) was used as an additional control. Sheep were injected intracamerally with 30 microL of each vector, either previously or after the induction of increased IOP with topical prednisolone or sub-Tenon triamcinolone under various protocols. IOP was measured with a Perkins tonometer. Inflammation was monitored by visual inspection. RESULTS In eyes in which IOP was already elevated to 24 to 30 mm Hg, injection of AdhGRE.MMP1 reduced IOP by 70% in 24 hours and to 10 to 13 mm Hg in 48 hours. In eyes with normal IOP (9-11 mm Hg), preinjection of the virus protected against the increase in IOP normally produced by the corticosteroid. IOP remained at a level of approximately 12 mm Hg for 5 days despite the continuous application of the corticosteroid. Injections of the control viruses had no hypotensive effects. There were no signs of ocular inflammation or discomfort to the animals. CONCLUSIONS A single dose of a gene therapy vector carrying an inducible metalloproteinase human gene can both protect against the IOP increase produced by corticosteroid instillation in the sheep model and quickly reverse the IOP increase previously elicited by the corticosteroid. These results are a first step toward a treatment of steroid-glaucoma with inducible overexpression of extracellular matrix modulator genes.
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Affiliation(s)
- Rosana Gerometta
- From the Departamento de Oftalmología, UNNE, Corrientes, Argentina
| | - Maria-Grazia Spiga
- the Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina; and
| | - Teresa Borrás
- the Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina; and
| | - Oscar A. Candia
- the Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York
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Abstract
PURPOSE OF REVIEW Over the past few years, the results of many studies have highlighted the risks and benefits of intravitreal injection of a number of medications, the most common being triamcinolone, antivascular endothelial growth factor (VEGF) agents, antibiotics, antivirals, antifungals, and methotrexate. The purpose of this review is to highlight the complications associated with these injections. RECENT FINDINGS Elevated intraocular pressure and glaucoma are the most common complications of intraocular triamcinolone. There is also an increased incidence of cataract formation/progression over time. The immunosuppressive effect of triamcinolone does not appear to increase the risk of endophthalmitis. Recent reports suggest that intravitreal anti-VEGF injections have a low complication rate. Similarly, antimicrobials also have low rates of injection-associated complications. SUMMARY Intravitreal injections play a critical role in daily ophthalmic practice. The overall risk of endophthalmitis and retinal detachment appears to be low and most of the commonly used drugs are well tolerated, even with repeat injection. Further long-term studies need to be performed to elucidate ways of increasing the safety of these procedures and medications.
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Gillies MC, Islam FMA, Larsson J, Pasadhika S, Gaston C, Zhu M, Wong TY. Triamcinolone-induced cataract in eyes with diabetic macular oedema: 3-year prospective data from a randomized clinical trial. Clin Exp Ophthalmol 2010; 38:605-12. [PMID: 20528977 DOI: 10.1111/j.1442-9071.2010.02341.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Mark C Gillies
- Department of Clinical Ophthalmology, Save Sight Institute, University of Sydney, Sydney, New South Wales, Australia.
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Kuo CH, McCluskey P, Gillies M. Pharmacotherapeutic efficacy of preservative-free intravitreal triamcinolone acetonide. Expert Opin Pharmacother 2010; 11:155-66. [PMID: 20001437 DOI: 10.1517/14656560903463885] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Preservative-free formulations of triamcinolone acetonide have recently been introduced to the market over concerns of local toxicity of the vehicle and preservatives, including benzyl alcohol in the original formulation, which was not designed for intraocular use. The pharmacokinetics and pharmacodynamics of intravitreal triamcinolone (IVTA) are discussed. The therapeutic effects of IVTA include improvement of visual acuity and reduction of macular edema. However, ongoing treatment is usually required to maintain its effects. The efficacy of IVTA for both FDA-approved and 'off-labeled' indications is reviewed. Elevation of intraocular pressure and cataract formation are the two major side effects of IVTA; these are manageable but require close long-term follow-up. More studies are required to determine the optimal dosage and treatment frequency in different posterior segment disease.
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Affiliation(s)
- Chih-Hung Kuo
- Save Sight Institute, Sydney Medical School,Sydney Eye Hospital, 8 Macquarie Street, Sydney 2001, NSW, Australia
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