Glucocorticosteroids are synthetic analogs of hormones produced by the suprarenal gland. Traditionally these drugs have been used for their anti-inflammatory properties and as immunosuppressants, for their ability to inhibit the activities of different cells types including lymphocytes, macrophages, neutrophiles, basophiles, endothelial vascular cells, and fibroblasts. The inhibitory effect of corticoids on fibroblast proliferation and endothelial vascular cells (1) had been observed in vitro and given rise to numerous possible therapeutic applications. However, these therapies were initially hindered by the inability to obtain sufficiently high doses of intraocular glucocorticoids using traditional topical or systemic administrations (2). In 1970, Machemer et al. (3) were the first to use intravitreal steroids in an animal model with retinal detachment. Intravitreal injections of triamcinolone were administered to obtain sufficient concentrations of intraocular corticoids inside the eye to prevent the development of proliferative vitreoretinopathy (PVR) after surgery. Other experimental models appeared later, evaluating the therapeutic effects of corticoid injections into the vitreous cavity (4,5).

Corticosteroids are known to reduce inflammation and tissue edema. Clinical studies suggest that intravitreal injections of steroids after the vehicle is removed may be an appropriate treatment for intraocular neovascular or edematous diseases (6, 7, 8 and 9). Steroids have been found to be potent inhibitors of vascular endothelial growth factor (VEGF) and may reduce the leakage of fluid from compromised capillaries in patients with maculopathy as well as inhibit neovascularization.

Triamcinolone acetonide (TA) is a corticosteroid with practically no water solubility which prolongs its presence in the vitreous nearly five times as compared to hydrocortisone (10). This increased media life makes it a useful alternative for the treatment of inflammatory ocular pathologies or other proliferative intraocular diseases.

Since the 1970s, many articles have been published evaluating the pharmacological effects of intraocular triamcinolone, as well as determining its safety and therapeutic effectiveness for a wide range of ophthalmologic pathologies (11, 12, 13, 14, 15 and 16).

In 1977, Perry et al. (17) published an article describing the apparent safety of an accidental intravitreal injection. A similar situation was described in 1993 by Gomez-Ulla et al. (18), when paramethasone acetate was inadvertently injected into the vitreous cavity during a subtenon’s placement of the medication; side effects were not noted. These incidents preceded planned intravitreal corticoid injection. The first intentional intraocular injections of triamcinolone in humans were administered in 1993 and 1994 by Dominguez et al. (19,20) for the treatment of pathologies like macular edema and choroidal neovascularization and in 1995 by Pendfold et al. (21) to treat 28 patients with exudative or wet age-related macular degeneration.

Intravitreal triamcinolone acetonide (IVTA) has been applied with an exponentially increasing frequency for various intraocular neovascular and edematous diseases, including diabetic macular edema (DME), proliferating diabetic retinopathy, and neovascular glaucoma due to proliferative diabetic retinopathy (PDR).

In DME, the edema may almost completely resolve, and visual acuity may increase as much as macular ischemia and the tissue destruction by the diabetic process may allow. For PDR and neovascular glaucoma, investigations have suggested an antiangiogenic effect of IVTA (22). The use of other steroids like intravitreal dexamethasone and slow release device such as sustained release fluocinolone intravitreal implant, are also areas of active research.

IVTA is a promising therapeutic method for DME that fails to respond to conventional laser photocoagulation (23, 24, 25, 26, 27 and 28).

Different techniques (nonfilter and filter techniques) applied to reduce the solvent agent benzyl alcohol (9.9 mg/ml) from a commercially prepared TA suspension were made (29).

Two different nonfilter techniques were used: sedimentation and centrifugation. Commercially prepared TA suspension was allowed to sediment overnight and 0.9 ml of the supernatant was extracted with a tuberculin syringe. The pellet was resuspended with 0.9 or 0.5 ml of balanced salt solution (BSS). In the other nonfilter technique, the commercial suspension was centrifuged at 3000 × g for 5 minutes; 0.9 ml of the supernatant was extracted with a tuberculin syringe and the pellet resuspended with 1 ml of BSS.

Filtered triamcinolone has been prepared by taking 0.62 ml from the commercial TA ampoule, following the technique described by Jonas (8,9). The extracted volume was placed in a tuberculin syringe (1 ml) filled with Ringer lactate solution. Two different syringe driven filter units were evaluated: a Millipore filter and a Pall filter. The selected filter was placed on the top of the syringe and most of the contents of the syringe were pressed through the filter, with the triamcinolone crystals remaining in the syringe. The syringe was refilled with Ringer lactate solution and the same procedure was repeated three times. In the end, 0.2 ml of the solution was left in the syringe.

Intravitreal injection of triamcinolone effectively reduces macular thickening due to diffuse DME, at least in the short term. However, in this chronic disease, the need to repeat intravitreal injections every 4 to 6 months will increase the risk of injection-related complications and may not be tolerated by the patients.

The injection technique is as follows. Topical anesthesia is applied to the ocular surface followed by preparation with 5% povidone iodine. A cotton-tipped applicator soaked in povidone iodine is then applied to the injection site, 3.5 mm posterior to the limbus in pseudophakic eyes and 4.0 mm posterior to the limbus in phakic eyes. TA is injected through the inferior pars plana at a dose of 4 mg (0.1 ml). A 30-gauge needle is used. Indirect ophthalmoscopy is used to confirm proper intravitreal localization of the suspension and perfusion of the optic nerve head (30).

The complications of IVTA include secondary ocular hypertension in about 40% of the eyes, medically uncontrollable high intraocular pressure (IOP) leading to antiglaucomatous surgery in about 1% to 2% (31,32), posterior subcapsular cataract and nuclear cataract leading to cataract surgery in
about 15% to 20%, especially in elderly patients within 1 year after injection (22,33), postoperative infectious endophthalmitis with a rate of about 1:500 or 1:1000 (34, 35 and 36), noninfectious endophthalmitis (36,37), and pseudo-endophthalmitis (38), which can recur even after successive injections (39). IVTA can be combined with other intraocular surgeries including cataract surgery (40), particularly in eyes with iris neovascularization due to diabetic retinopathy.

Pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peeling has also been advocated for the treatment of diabetic maculopathy (41), the reasons being mainly to relieve anteroposterior vitreomacular traction, tangential traction, as well as to remove interleukin 6 (IL-6), VEGF and other vasopermeable factors from the vitreous, improve microcirculation, and improve oxygenation (42, 43, 44 and 45). The benefit of ILM peeling is that it ensures that all posterior hyaloidal traction has been removed (46). When laser photocoagulation and TA treatment is not effective for diabetic maculopathy, vitrectomy with the complete removal of the posterior hyaloid face, including possible removal of the ILM, should be considered (47, 48 and 49). TA greatly improves the visualization of the ILM. TA is used during vitrectomy to visualize the hyaloid. After the posterior hyaloid is surgically separated from the optic nerve head and posterior retina, TA suspension is injected over the posterior pole and an intraocular forceps is used to peel the ILM in a circumferential manner. The peeled area is seen as an area lacking white specks.

Several complications of advanced diabetic retinopathy can be treated surgically. Vitrectomy can clear media opacities, relieve traction on the retina, and make adequate laser treatment of the retina possible. IVTA may be an additional tool in PPV for PDR (50

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