If the upper boundary is less than 0. For missing data, the worst observed value will be imputed for triamcinolone patients and the best value for dexamethasone patients. A sensitivity analysis will be performed with multiple imputation. For secondary end points, the mean visual analogue scale score evaluating the moment of injection will be compared between groups using a linear mixed model; the score for the moment tolerable, uncomfortable or very unpleasant will be compared using the Mantel—Haenszel stratified Chi-squared test.
Duration of injection efficacy duration is determined by the reappearance of oedema will be compared between the groups using the Van Elteren test semiquantitative outcome. Comparisons between the groups will be performed using Chi-squared or Fisher tests for intermittent ocular hypertension, cataract, endophthalmitis, glycaemic and blood pressure imbalances in both arms.
There will be no imputation for missing data for these secondary end points. The ICERs will be estimated along with their corresponding acceptability curves, i. Sensitivity analyses will be performed for all end points, adjusted for the duration of macular oedema. All statistical tests will be bilateral. For secondary endpoints, a P value less than 0. As this is a noninferiority study, the analyses will be carried out on the intent-to-treat population and on the per-protocol population.
The intent-to-treat population consists of all randomised patients in the study. The per-protocol population includes the most compliant patients, based on compliance with the inclusion and exclusion criteria, absence of major deviations from the protocol and availability of the main criterion.
This TRIOZ trial aims to demonstrate the noninferiority of subconjunctival triamcinolone injections compared to intravitreal dexamethasone implants. Noninferiority will be evaluated in terms of the difference in macular thickness in the treated eye between D0 and M2. Preliminary data observed retrospectively in Nantes between and in 25 patients who received triamcinolone injections showed a decrease of 0. The difference in macular thickness between D0 and M2 is assumed to be the same in the two groups and the common standard deviation is set at 0.
Based on these assumptions, patients are needed to demonstrate the noninferiority of triamcinolone compared to dexamethasone. Randomisation will be conducted openly and stratified by centre. It will be performed according to a ratio and balanced by blocks. The random numbers will be generated by computer. Subjects are randomised into blocks as the allocation progresses, a block being a subgroup of predetermined size within which there is a random allocation of patients.
The software used for the randomisation is SAS version 9. The randomisation key is known only to the biostatistician and the data managers to make it impossible for the investigator to assign a particular treatment. As mentioned above, for logistical reasons the trial is now open-label. As Karanicolas et al.
Based on the randomisation, the batch used will be replaced by the pharmacy of CHU Nantes. The treatments will be kept at the pharmacy in each study centre for issue on the prescription of the investigator during the treatment visit. There are no pharmacokinetic data in the literature for triamcinolone administered subconjunctivally.
Inflammatory macular oedema, a chronic and recurrent pathology, requires regular ophthalmological monitoring at least every 6 months, regardless of the type of treatment administered. The investigator must ensure that the information entered in this report is accurate and clear. After receiving an unexpected SAE report, the sponsor notifies the authorities.
Once a year, the sponsor prepares an annual safety report. Members of the committee who are competent in the field of clinical trials pathology and methodology are not involved in the study. In any event, written confirmation will be sent to the coordinating investigator for the study specifying the reasons for early termination and to the principal investigator of each centre, if applicable.
All patients in the study will be informed and will be required to complete their early discharge visit. The clinical study will be conducted in accordance with the relevant versions of the French Public Health Code, national and international Good Clinical Practice guidelines, and the Declaration of Helsinki, each in the applicable version.
In compliance with French law, the study protocol was submitted to the French regulatory authority ANSM and was approved on 31 August The clinical protocol has been writeen according to Spirit check-list see Additionnal file 5. The amended protocol should be a dated, updated version. If necessary, the information form and consent form should be amended.
As required, the sponsor has provided an insurance policy to cover the financial consequences of its civil liability in accordance with the regulations. It has been possible to carry out the protocol and the trial thanks to an Executive Committee which includes a Scientific Committee and a Steering Committee.
The Scientific Committee was created by M. Weber and its membership comprises external experts in this pathology, biostatisticians and methodologists, the medical economist and the project manager of the clinical investigation centre CIC It is coordinated by Dr. The Steering Committee is composed of the members of the Scientific Committee, except the external experts, and with the addition of the data management team, the nurse study coordinator from the Ophthalmology Department of CHU Nantes who coordinates assistance for patient inclusion in the other centres, and the monitoring Clinical Research Assistant CRA.
Inspectors will check the documents, logistics, records and any other resources that the authorities consider to be associated with the clinical trial and that may be located at the trial site itself. The trial results will be published in international ophthalmological, medical and scientific journals and presented at national and international conferences.
In practice, the Scientific Committee will be among the authors of the publication, as will the investigators who have included the most patients in the trial. The trial sponsor and the French Ministry of Health, which provided the grant, must be cited in the publication. Demonstration of the efficacy and safety of subconjunctival triamcinolone injections will enable their continued use at a time when the marketing authorisation for an intravitreal device requires the intraocular delivery of a unique, expensive compound, exposing the patient to a rare risk of endophthalmitis and retinal detachment, while the relative efficacy and safety of these approaches have never been compared.
The European Union has established a tight safety net. No medicinal product may be marketed in a member state unless the competent authorities of that state have issued a marketing authorisation [ 33 ]. Recently, a control framework for medically justified off-label prescriptions has been implemented in France. Act no. It also introduces a second, unique derogating provision into French law pursuant to Article L. The French health authorities have amended the RTU framework in order to authorise the reimbursement of a drug used off-label, despite the existence of licensed therapeutic alternatives, because of the burden of licensed drugs on the health care system.
The other significant difference is the striking disparity in the cost of the two drugs. We hope, therefore, that if this clinical trial proves the efficiency of subconjunctival triamcinolone injections the French Health Authorities will authorise the reimbursement of this drug. This trial is still ongoing; patient inclusion is not yet complete.
The updated protocol is at version 10 on 7 July The first patient was included on 13 January Recruitment by the investigating centres is planned to continue until 13 October and the study period will end in March Data sharing is not applicable to this paper as no datasets were generated or analysed during the current study. The data from the completed trial will not be shared and will only be transmitted to the sponsor. Data collected during the test may be processed electronically, in accordance with the requirements of the CNIL compliance with reference methodology MR Impact of macular edema on visual acuity in uveitis.
Article Google Scholar. The possible impact of uveitis in blindness: a literature survey. Br J Ophthalmol. Degree, duration, and causes of visual loss in uveitis. Causes and frequency of blindness in patients with intraocular inflammatory disease. Rothova A. Inflammatory cystoid macular edema. Curr Opin Ophthalmol. Dexamethasone concentration in vitreous and serum after oral administration. Am J Ophthalmol. Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate.
Peribulbar corticosteroid injection: vitreal and serum concentrations after dexamethasone disodium phosphate injection. High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection. Biochemical quantification of triamcinolone in subconjunctival depots. Arch Ophthalmol Chic Ill Turpin C. The effects of posterior subtenon injection of triamcinolone acetonide in patients with intermediate uveitis.
Complications and safety profile of posterior subtenon injection of triamcinolone acetonide. Survey of triamcinolone acetonide for ocular diseases in Japan. Nippon Ganka Gakkai Zasshi. Evaluation of the safety and performance of an applicator for a novel intravitreal dexamethasone drug delivery system for the treatment of macular edema.
Retina Phila Pa. The dexamethasone drug delivery system: indications and evidence. Adv Ther. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.
Functional and anatomical results after a single intravitreal Ozurdex injection in retinal vein occlusion: a 6-month follow-up — the SOLO study. Acta Ophthalmol. Retreatment with Ozurdex for macular edema secondary to retinal vein occlusion. Eur J Ophthalmol. J Fr Ophtalmol. Outcome of intravitreal triamcinolone in uveitis. Vision-related functioning outcomes of dexamethasone intravitreal implant in noninfectious intermediate or posterior uveitis. Invest Ophthalmol Vis Sci.
Normative comparison of patient-reported outcomes in patients with noninfectious uveitis. JAMA Ophthalmol. Logarithmic transformation of spectral-domain optical coherence tomography data in uveitis-associated macular edema. A proposed method of logarithmic transformation of optical coherence tomography data for use in clinical research. Chevalier J.
France: Paris IX Dauphine; Chevalier J, de Pouvourville G. Valuing EQ-5D using time trade-off in France. Estimating mean QALYs in trial-based cost-effectiveness analysis: the importance of controlling for baseline utility. Health Econ. Practical tips for surgical research: blinding: who, what, when, why, how? Google Scholar. Cited 28 Sept N Engl J Med. Department of Health and Human Services. Medicare payments for drugs used to treat wet age-related macular degeneration. Download references.
This study was supported by a grant from the French Ministry of Health awarded in under the Hospital Clinical Research Programme , no. This grant is allocated following peer review. The research projects selected by this call for tenders must contribute to medical progress and the improvement of the health care system.
The funding body will be mentioned in the acknowledgements as having funded the research but does not get involved in the study, analysis or interpretation of the data. You can also search for this author in PubMed Google Scholar.
CC and AP contributed equally to the drafting of the manuscript. V-PR wrote the medical economic analyses. AC and AJ assisted with pharmacovigilance for the trial. All authors read and approved the final manuscript. Correspondence to Alexandra Poinas. All patients participating in the study will be given oral and written information about this trial and will sign the informed consent form.
The authors declare that they have no competing interests. This study is considered to be externally funded as MW has been awarded government funding via a funding body. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Major ocular complications of steroids by route of administration from Turpin et al. SPIRIT checklist: recommended items to address in a clinical trial protocol and related documents.
Reprints and Permissions. Couret, C. Comparison of two techniques used in routine care for the treatment of inflammatory macular oedema, subconjunctival triamcinolone injection and intravitreal dexamethasone implant: medical and economic importance of this randomized controlled trial. Trials 21, Download citation. Received : 18 October Accepted : 11 January Published : 10 February Skip to main content. Purpose: To study the dexamethasone level reached in human vitreous after a peribulbar injection of 5 mg of dexamethasone disodium phosphate and to assess its systemic uptake.
Methods: In a prospective study, 61 eyes of 61 patients scheduled for vitrectomy received a single peribulbar injection of 5 mg of dexamethasone disodium phosphate at varied intervals before surgery. At the start of vitrectomy, an undiluted vitreous sample was taken. In 22 patients, multiple serum samples were collected. Dexamethasone concentrations were measured by radioimmunoassay. The physiologic cortisol concentration was determined in the vitreous of 12 eyes of 12 patients who did not receive dexamethasone.
The mechanism of breakdown of the blood retina barrier at the level of the retinal capillaries and the retinal pigment epithelium may be due to changes to tight junction proteins such as occludin. The increase in retinal capillary permeability and subsequent retinal edema may be the result of a breakdown of the blood retina barrier mediated in part by vascular endothelial growth factor VEGF , a 45 kD glycoprotein.
Aiello et al, demonstrated in an in vivo model that VEGF can increase vascular permeability. The effect of intravitreal administration of VEGF on retinal vascular permeability was assessed by vitreous fluorophotometry. In all 15 eyes receiving an intravitreal injection of VEGF, a statistically significant increase in vitreous fluorescein leakage was recorded.
In contrast, control eyes, which were fellow eyes injected with vehicle alone, did not demonstrate a statistically significant increase in vitreous fluorescein leakage. Antonetti et al, demonstrated that VEGF may regulate vessel permeability by increasing phosphorylation of tight junction proteins such as occludin and zonula occluden 1. Sprague-Dawley rats were given intravitreal injections of VEGF and changes in tight junction proteins were observed through Western blot analysis.
Treatment with alkaline phosphatase revealed that these changes were caused by a change in phosphorylation of tight junction proteins. This model provides, at the molecular level, a potential mechanism for VEGF-mediated vascular permeability in the eye.
Similarly, in human non-ocular disease states such as ascites, VEGF has been characterized as a potent vascular permeability factor VPF. Vinores et al, using immunohistochemical staining for VEGF, demonstrated that increased VEGF staining was found in retinal neurons and retinal pigment epithelium in human eyes with diabetic retinopathy.
As the above discussion suggests, attenuation of the effects of VEGF provides a rationale for treatment of macular edema associated with diabetic retinopathy. Corticosteroids, a class of substances with anti-inflammatory properties, have been demonstrated to inhibit the expression of the VEGF gene. In a study by Nauck et al, the platelet-derived growth-factor PDGF induced expression of the VEGF gene in cultures of human aortic vascular smooth muscle cells was abolished by corticosteroids in a dose-dependent manner.
This study was performed using primary cultures of human pulmonary fibroblasts and pulmonary vascular smooth muscle cells. As discussed above, corticosteroids have been experimentally shown to down regulate VEGF production and possibly reduce breakdown of the blood-retinal barrier. Similarly, steroids have anti-angiogenic properties possibly due to attenuation of the effects of VEGF.
Both of these steroid effects have been utilized. For example, triamcinolone acetonide is often used clinically as a periocular injection for the treatment of cystoid macular edema CME secondary to uveitis or as a result of intraocular surgery. In animal studies, intravitreal triamcinolone acetonide has been used in the prevention of proliferative vitreoretinopathy and retinal neovascularization.
Intravitreal triamcinolone acetonide has been used clinically in the treatment of proliferative vitreoretinopathy and choroidal neovascularization. Scans were 6 mm length and included the 6 radial line pattern for quantitative measures and the cross hair pattern to o'clock for qualitative assessment of retinal morphology. Negative changes represent a decrease in retinal thickening. Negative changes represent a worsening in visual acuity.
Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. To be eligible, the following inclusion criteria must be met:. A patient is not eligible if any of the following exclusion criteria are present:. Patient is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next 8 months.
The patient must have at least one eye meeting all of the inclusion criteria a-e and none of the exclusion criteria f-t listed below:. Media clarity, pupillary dilation, and patient cooperation sufficient for adequate fundus photographs and OCT. History of major ocular surgery including cataract extraction, scleral buckle, any intraocular surgery, etc.
History of YAG capsulotomy performed within 2 months prior to randomization. History of open-angle glaucoma either primary open-angle glaucoma or other cause of open-angle glaucoma; note: angle-closure glaucoma is not an exclusion. A patient may have two "study eyes" only if both are eligible at the time of randomization. Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information.
Search for terms. Save this study. Warning You have reached the maximum number of saved studies A Pilot Study of Peribulbar Triamcinolone Acetonide for Diabetic Macular Edema Peribulbar The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U. Federal Government.
Read our disclaimer for details. Results First Posted : June 14, Last Update Posted : August 26, Study Description. Patients with one study eye will be randomly assigned stratified by prior laser with equal probability to one of five treatment groups: Focal laser photocoagulation modified ETDRS technique Posterior peribulbar injection of 40 mg triamcinolone Kenalog Anterior peribulbar injection of 20 mg triamcinolone Posterior peribulbar injection of 40 mg triamcinolone followed after one month by laser Anterior peribulbar injection of 20 mg triamcinolone followed after one month by laser For patients with two study eyes both eyes eligible at the time of randomization , the right eye stratified by prior laser will be randomly assigned with equal probabilities to one of the five treatment groups listed above.
Show detailed description. Hide detailed description. Detailed Description:. Drug Information available for: Triamcinolone diacetate Triamcinolone acetonide Triamcinolone Triamcinolone hexacetonide. FDA Resources. Arms and Interventions. Posterior peribulbar injection of 40 mg triamcinolone Kenalog. Anterior peribulbar injection of 20 mg triamcinolone. Posterior peribulbar injection of 40 mg triamcinolone followed after one month by laser. Anterior peribulbar injection of 20 mg triamcinolone followed after one month by laser.
Outcome Measures. Change in visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the electronic Early Treatment for Diabetic Retinopathy Study E-ETDRS technique. Eligibility Criteria. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision.
Study Level Exclusion Criteria A patient is not eligible if any of the following exclusion criteria are present: History of chronic renal failure requiring dialysis or kidney transplant. A condition that, in the opinion of the investigator, would preclude participation in the study e.
Patients in poor glycemic control who, within the last 4 months, initiated intensive insulin treatment a pump or multiple daily injections or plan to do so in the next 4 months should not be enrolled. Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at the time of study entry.
Known allergy to any corticosteroid or any component of the delivery vehicle. History of systemic e. Whereas some researchers reported an association between the MYOC gene and steroid-induced glaucoma [ 45 , 46 ], others reported no such association [ 47 , 48 ]. Finally, the MYOC genetic mutation was negatively associated with steroid-induced glaucoma in a recent study [ 49 ].
This is reasonable because RVO is known to develop in elderly people. Regarding risk factors for IOP elevation, younger people are widely known to be at higher risk [ 34 — 37 ]. Baseline IOP values in these patients were The results from our study with a large number of patients were similar; younger age and higher baseline IOP were risk factors for IOP elevation.
From the analyses of IOP elevation under the steroid fixed condition, the risk factors were same; younger age and higher baseline IOP. However, a lower incidence of DME was identified as a risk factor with a fixed steroid dose, whereas a higher incidence of DME was a risk factor under a variable steroid dose; this suggested that IOP might increase in association with the dose of TA, especially in patients with DME.
An absolute IOP elevation i. However, a relatively large difference in IOP may induce an effect on ganglion cells. In the present study, This steroid dose-dependent elevation in IOP was previously reported [ 35 ]. We acknowledge several limitations to this study.
First, the IOP measurement device was not standardized among hospitals. Second, the time to measure IOP was not standardized among hospitals because our study was a retrospective multicentre study. However, this study included a large number of patients, such that the respective risks of IOP elevation and increase are likely to be accurate and representative.
We thank Tadanobu Yoshikawa, M. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Methods This was a multicentre retrospective study of the medical records of patients men eyes ; mean age: Results IOP elevation was observed in eyes Funding: The authors received no specific funding for this work.
Introduction Subtenon triamcinolone acetonide injection STTA was initially reported as treatment for optic neuritis [ 1 ], and has been used to treat diabetic macular oedema DME [ 2 — 10 ], cystoid macular oedema CME due to retinal vein occlusion RVO [ 11 — 13 ], uveitis [ 14 — 17 ], scleritis[ 18 , 19 ], neuroretinitis [ 20 ], and CME following intraocular surgery [ 21 ]. Study protocol Data were extracted from medical records in the various hospitals and sent to the data centre in the Department of Ophthalmology, Hyogo College of Medicine.
IOP measurements IOP measurements were performed using a Goldman tonometer or non-contact type tonometer in each hospital. Statistical analyses For continuous variables, the mean, standard deviation, median, and range were calculated. Download: PPT. Table 4. Discussion In this study, we analysed the proportions of eyes with IOP elevation after STTA in a sample of more than 1, Japanese patients, and assessed the characteristics associated with IOP elevation in those patients.
Supporting information. S1 Dataset. Acknowledgments We thank Tadanobu Yoshikawa, M. References 1. Sub-tenon steroid injection for optic neuritis. Trans Am Acad Ophthalmol Otolaryngol. Posterior subtenon triamcinolone acetonide for refractory diabetic macular edema. Am J Ophthalmol. Comparison of intravitreal versus posterior sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema.
Intravitreal vs. BMC Ophthalmol. View Article Google Scholar 5. Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: a pilot study. Posterior sub-tenon triamcinolone for refractory diabetic macular edema: a randomized clinical trial. Eur J Ophthalmol. Posterior subtenon and intravitreal triamcinolone acetonide for diabetic macular edema. J Diabetes Complications. Posterior sub-Tenon's capsule triamcinolone acetonide injection for the treatment of diabetic macular edema.
J Ocul Pharmacol Ther. Drug reflux during posterior subtenon infusion of triamcinolone acetonide in diffuse diabetic macular edema not only brings insufficient reduction but also causes elevation of intraocular pressure. Graefes Arch Clin Exp Ophthalmol. Injection of triamcinolone acetonide into the posterior sub-tenon capsule for treatment of diabetic macular edema.
Trans-Tenon's retrobulbar triamcinolone acetonide injection for macular oedema related to branch retinal vein occlusion. Br J Ophthalmol. Early treatment of severe cystoid macular edema in central retinal vein occlusion with posterior sub-tenon triamcinolone acetonide. Trans-tenon retrobulbar triamcinolone infusion for chronic macular edema in central and branch retinal vein occlusion.
Efficacy and complications of intravitreal injection of triamcinolone acetonide for refractory cystoid macular edema associated with intraocular inflammation. Jpn J Ophthalmol. Clinical trial to compare efficacy and side-effects of injection of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in the management of posterior uveitis. Clin Exp Ophthalmol. The effects of posterior subtenon injection of triamcinolone acetonide in patients with intermediate uveitis.
Real-world evidence of treatment for relapse of noninfectious uveitis in tertiary centers in Japan: A multicenter study. Evaluation of sub-Tenon triamcinolone acetonide injections in the treatment of scleritis. Park YH. Sub-tenon triamcinolone acetonide injection in the treatment of scleritis. Combined intravitreal bevacizumab and triamcinolone acetonide injection for idiopathic neuroretinitis. Ocul Immunol Inflamm. A comparison of retrobulbar versus sub-Tenon's corticosteroid therapy for cystoid macular edema refractory to topical medications.
Jonas JB, Sofker A. Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular edema. Intravitreal triamcinolone acetonide for macular oedema due to central retinal vein occlusion. Intravitreal triamcinolone acetonide for ischaemic macular oedema caused by branch retinal vein occlusion. Acute endophthalmitis following intravitreal triamcinolone acetonide injection.
Arch Ophthalmol. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Complications and safety profile of posterior subtenon injection of triamcinolone acetonide.
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Injection into the orbital floor is easily performed in the clinic with a 25 mm gauge needle. It is well tolerated and carries only a very small risk of globe perforation, as the needle is directed away from the globe at all times. It has a duration of action of up to 3 months, but it can require 6 weeks to take full effect. This may not be fast enough for patients with severe vitritis or CME, in whom a more immediate therapeutic effect is desirable. In addition, some cases of vitritis and CME prove resistant even to repeated injections of periocular steroid; patients are declared refractory to treatment if they fail to respond to 3 separate injections given at 6-week intervals.
Like other modes of corticosteroid delivery, periocular corticosteroids are linked with the development of elevated intraocular pressure IOP and cataract. IVTA injection is of particular use in 2 groups of patients: those with severe vitritis or CME that is unlikely to respond rapidly to periocular corticosteroids, and those with inflammation that has already proved refractory to such treatment. Indeed, small case series have demonstrated that IVTA has beneficial effects in the treatment of refractory CME associated with uveitis, including in patients previously treated with periocular corticosteroids and second-line immunosuppressive agents.
However, when used, it takes effect rapidly and has a duration of action of weeks. IVTA is also useful in establishing whether there is a reversible component to visual loss. Visual loss of inflammatory origin can be considered truly refractory to immunosuppression only if there is no improvement in response to IVTA, in which case discontinuing systemic therapy may be appropriate. However, the use of intravitreal corticosteroids can cause side effects.
However, many clinicians now consider this only a relative contraindication, particularly with the advent of corticosteroid implants. Filtration surgery in these patients has a high success rate, probably owing to the corticosteroid influence, and the visual benefits of treatment may still outweigh the risks, at least in the short term.
Infectious culture-positive endophthalmitis is rare, occurring in zero to 0. There is continuing debate regarding the contribution to this occurrence of the preservatives in the preparation, but we have found sterile endophthalmitis to be a rare development. Removing preservatives by washing prior to use also reduces the dose given 7 and may increase the risk of bacterial contamination.
There is also debate over the dosage: 2 mg, 4 mg, and 25 mg doses of triamcinolone have all been reported, although most of the 25 mg doses reported were subsequently washed, significantly reducing the actual dose delivered. We use 4 mg, as a 2 mg dose does not allow the treating clinician to determine whether a patient who fails to respond is refractory to treatment or has simply been undertreated, and larger doses appear to provide no discernable extra benefit.
To avoid the need for recurrent intravitreal corticosteroid injections in patients with chronic disease, sustained-release devices have been developed, 2 of which are currently undergoing phase 4 trials. The Posurdex implant is an injected intravitreal biodegradable polymer that releases low-dose dexamethasone over a period of approximately 6 months, and the Retisert device is a surgically placed intravitreal insert that releases fluocinolone acetonide over a period of 2.
Both can result in a significant rise in IOP; the Retisert implant is associated with a very high rate of cataract surgery and trabeculectomy. Essentially, the systemic side effects of traditional immunosuppression are exchanged for treatable local complications. The Posurdex trial is due to report in , and 3-year data is starting to become available for the Retisert implant.
While periocular corticosteroid injections remain the mainstay of treatment for unilateral vitritis or CME on the grounds of their relative safety, intravitreal therapy has made treatment possible of disease that had previously been considered refractory.
The trend toward intravitreal treatment is likely to continue with the introduction into clinical practice of long-acting steroid implants that, it is hoped, will prove both effective and convenient for patients with chronic sight-threatening disease requiring long-term immunosuppression. References 1. Clinical trial to compare efficacy and side-effects of injection of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in the management of posterior uveitis.
Clin Experiment Ophthalmol. Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study. The efficacy of glucocorticoids may be affected by several factors, particularly the administration route. For instance, systemically administered glucocorticoids may have multiple complications and side effects 5. However, retrobulbar or subconjunctival injection of corticosteroids for TAO treatment may avoid systemic complications 6. Previous studies have revealed the benefits of periocular injection of methylprednisolone and triamcinolone in improving the symptoms of TAO 6 , 7.
At present, studies evaluating the effectiveness of various corticosteroids used locally to treat Chinese patients with TAO are scarce. Therefore, the present study aimed to retrospectively analyze the clinical outcomes of periorbital injection of triamcinolone acetonide TA combined with dexamethasone DEX in Chinese patients with TAO and also assess factors that affect therapeutic effectiveness. The following exclusion criteria were applied: i Contraindication to steroids diabetes or systemic hypertension, gastritis, psychosis or pregnancy ; ii previous treatment of TAO with steroids or radiation.
Patients were included regardless of their endocrine status. This retrospective study was performed according to the Declaration of Helsinki, and approved by the review board of West China Hospital, Sichuan University Chengdu, China. Patients provided written informed consent for the publication of the images and data in this retrospective study.
The dose of TA was determined referring to previous studies 6. The patient was placed in the supine position and sterile local anesthetic drops were placed in the eye. Subsequently, the eyelids were cleaned with povidone-iodine solution. Mixed corticosteroids were injected into the interior lateral and superior inner quadrants of the orbit, vertically and slowly by the same physician using a gauge disposable needle, avoiding the eyeball and surrounding vessels.
The eye was closed, with light pressure immediately placed on the periorbital area for min after needle withdrawal in order to spread the steroids and prevent hematoma formation. The patient's pulse and ocular condition were also observed.
All patients were followed up and assessed one month after each injection. Ocular complications linked to glucocorticoid injection and systemic adverse reactions were recorded. All patients underwent a monthly follow-up for half a year, followed by quarterly follow-up for at least another year.
The upper normal limit was determined to be 15 mm in oriental populations Substantial improvement very good effectiveness was defined as changes in all major and auxiliary outcome measures and improvement in subjective symptoms. No change was defined as no improvement in any outcome measure after periorbital injection. Variables with a skewed distribution were tested by the Wilcoxon signed-rank test or the Kruskal-Wallis H test. Bivariate analysis was performed by the non-parametric Mann-Whitney U-test or Kruskal-Wallis test followed by Dunn's test to examine the associations of effectiveness with predictive factors.
The relevant independent variables were as follows: Demographic characteristics, including gender and age; lifestyle parameters such as smoking and alcohol consumption; a thyroid function-associated factor, i. Variable selection was based on a previous study assessing the potential of variables for predicting the clinical outcome A total of patients eyes were included.
There were males The average duration of ocular signs and TAO symptoms was A total of patients Furthermore, 35 cases 9. Among the patients treated with anti-thyroid drug, 98 recovered to have normal thyroid function. Those patients with thyroid dysfunction were advised to receive medical endocrinology treatment during the therapy for TAO.
A total of 41 All patients had varying degrees of eyelid swelling, retraction and sluggishness. Furthermore, 38 patients suffered from corneal epithelial defects without optic nerve involvement. The clinicopathological characteristics of the patients are summarized in Table II. Disease severity classification was referred to the criterion of Table I.
Thyroid-associated ophthalmopathy signs in patients are improved after treatment. A-D Female patient, 23 years old; A and B the right eye with A upper eyelid retraction and B drooping eyelid prior to treatment. C No eyelid retraction and D no drooping after periorbital injection of triamcinolone acetonide and dexamethasone. E-H Female patient, 36 years old; E right eye with upper eyelid swelling, eyelid retraction and conjunctival edema prior to treatment; F drooping eyelid prior to treatment; normal eyelid when looking forward G and looking downward H after periorbital injection.
A total of patients received periorbital injection therapy with a month follow-up period. Among the patients who experienced tearing, photophobia and blurred vision, Pain due to eye movement was relieved in 31 of the 43 cases Among the cases with eyelid swelling, Eyelid retraction was improved in Upper eyelid sluggishness in A total of 49 Eye motility disturbance was improved in 29 The patients received at least two injections and stopped when no significant effect was observed after the last injection.
No significant difference in treatment effectiveness was observed between the 3 and 4 injection groups. These results indicated that the rate of patients with substantial improvement increased with the number of injections Table II. The patients were stratified into groups of mild to severe TAO based on the degree of proptosis, diplopia and visual acuity impairment, according to the assessment criteria of TAO severity Table I.
A total of cases Thus, thyroid function influenced the response to treatment. MT, medical treatment. A total of 5 subjects developed subcutaneous ecchymosis, which was relieved gradually within two weeks during follow-up by pressure manipulation using swabs to hemostasis. Furthermore, 3 cases exhibited conjunctival edema that was eased after applying swabs with erythromycin ointment to return the prolapsed conjunctiva back into the eyelid.
In addition, 1 case developed a self-limiting subconjunctival hemorrhage. A total of 31 cases 8. Furthermore, 2 post-menopausal females 49 and 55 years old had a menstruation after treatment. In addition, menstrual disorders occurred in 11 out of 90 A total of 2 patients had moon face symptoms. No other ocular or systemic adverse reactions, including infection, penetrating eye, eye muscle motility disturbance restriction of eye movement and cerebral vascular events were observed 9.
Furthermore, the rate at which patients experienced an effective outcome significantly increased with the number of periorbital injections. However, age and drinking habits were not significantly associated with the effectiveness of periorbital injection. According to the multivariate analyses, the adjusted factors that significantly and favorably associated with treatment efficacy in the ordinal logistic regression were female vs.
The present study demonstrated the effectiveness of periorbital injection of corticosteroids, namely TA and DEX in combination. This clinical outcome was affected by several factors, including gender, smoking, as well as disease severity and activity. Treatment options for different TAO stages remain controversial, as systemic administration of glucocorticoids may exert numerous side effects 5. The present study demonstrated that periorbital injection of TA combined with DEX improved the symptoms of TAO with limited systemic adverse effects and side effects.
TA, an insoluble long-acting synthetic fluorinated corticosteroid, is slowly absorbed into the eye; its potency is 5 times higher than that of cortisol, with effects sustained for weeks or even longer Thus, TA injection is required every weeks. DEX is also a long-acting corticosteroid with a potency 25 times that of short-acting products 20 , and combination with TA requires reduced injection dosages and times in patients with mild to moderate TAO compared with each corticosteroid applied as a monotherapy.
According to our own experience, combination therapy of TA and DEX for patients with TAO may also achieve a prolonged local steroid concentration and higher potency to inhibit the inflammation compared with the use of TA only. In addition, a previous study indicated that periorbital injection of a combination of TA and DEX may improve lid retraction and limitation of eye movement in patients with TAO After periorbital injection, the symptoms of TAO exhibited various levels of improvement.
Among TAO signs, substantial remissions in eyelid swelling, upper eyelid lag and retraction were achieved in the present study. Proptosis, involvement of eye muscles and corneal epithelial defects were also improved to varying degrees. Next, patients with active TAO were divided into groups based on disease severity mild to severe according to the degree of proptosis, diplopia and visual acuity impairment, which referred to the assessment criterion of TAO severity Although substantial improvement was achieved in patients with mild to moderate proptosis, eye muscles were not successfully improved.
These results indicated that periorbital injection of corticosteroids was more effective in patients with mild to moderate TAO. The results also indicated that patients with TAO injected 3 or 4 times had a more pronounced improvement than those who received two injections.
This suggests that the effectiveness of periorbital injection of these corticosteroids is cumulative. Next, factors potentially predicting clinical outcome were assessed. Indeed, the current treatment was more effective in female patients compared with males, while smoking decreased the therapeutic effectiveness. A previous meta-analysis revealed a strong association of cigarette smoking with TAO progression and deterioration In addition, smoking was previously reported to attenuate the effectiveness of systemic glucocorticoids as well as orbital radiotherapy However, the pathogenic mechanisms underlying the effects of smoking in TAO remain to be fully elucidated.
Thus, it is imperative for patients with TAO to quit smoking. The present study also demonstrated that patients with mild or moderate TAO were more likely to exhibit improvement after treatment compared with cases of severe TAO. These results indicated that periorbital injection of corticosteroids alone in cases of severe TAO may not suffice and should be combined with systemic administration of glucocorticoids or orbital radiotherapy.
Furthermore, patients with a shorter course of TAO responded better to treatment than those with a longer course, although the duration of TAO was not significantly associated with the effectiveness of the treatment. Therefore, early treatment is also recommended for TAO. Previous studies indicated that progressive exacerbation of TAO characterized by lymphocyte infiltration may occur over months and is considered the active progressive phase when anti-inflammatory therapy is indicated This is followed by a weakened inflammatory activity and a static phase, which may lead to orbital tissue fibrosis.
The severity of TAO reflects the degree of orbital inflammation, which is remedied by the anti-inflammatory function of glucocorticoids In addition, thyroid dysfunction may increase the risk of aggravation of TAO and reduce the effectiveness of periorbital injection. Previous studies revealed that thyroid-stimulatory hormone receptor antibody and thyroxine or triiodothyronine levels are associated with the worsening of TAO However, further investigation is required to confirm the roles of the above factors in the development of TAO.
It is known that I administration triggers hypothyroidism and autoimmune inflammation, leading to the deterioration of TAO The risk of radioactive iodine therapy is higher in comparison with that of anti-thyroid drugs 29 ,