Corticosteroids in Endophthalmitis

Fig. 22.1
Structure of corticosteroid

Mechanism of Action

Corticosteroids exert their anti-inflammatory activity through the following mechanisms:
  • They cause constriction of blood vessels, which reduces the vascular permeability, thereby reducing leakage of fluid, proteins and inflammatory cells into the target site [10].
  • Corticosteroids prevent adherence of neutrophils to the vascular endothelium, thus decreasing their mobility and making them less accessible to the site of inflammation [11].
  • They stabilize intracellular lysosomal membranes and inhibit the expression of various damaging enzymes [12].
  • Stabilization of mast cell and basophil membranes by corticosteroids plays an important role in inhibiting the process of degranulation and further release of inflammatory mediators [12].
  • Corticosteroids inhibit macrophage recruitment and migration and also interfere with the ability of macrophages to process antigens [13].
  • Corticosteroids inhibit phospholipase A2 resulting in inhibition of arachidonic acid degradation. Thus, subsequent synthesis of prostaglandins and leukotrienes by cyclooxygenase and lipoxygenase pathways is affected [14].

Role of Mineralocorticoids in Inflammation

Aldosterone is a mineralocorticoid receptor agonist which can be expressed by cells of the immune system and has been associated with release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis [15]. Normally, in the body, mineralocorticoid receptor is co-expressed with 11β-hydroxysteroid dehydrogenase 2 enzyme, which converts active cortisol into inactive glucocorticoids. The close proximity of this enzyme and mineralocorticoid receptor has been proposed to prevent the receptor activation by glucocorticoids [16, 17].
Under physiological conditions, the circulating glucocorticoid concentrations are 100–1000 times higher than those of aldosterone. Thus, the mineralocorticoid receptor activity is most likely controlled by glucocorticoids and not aldosterone [18]. To avoid the adverse effects caused by excessive mineralocorticoid receptor action, synthetic glucocorticoids have been designed to activate glucocorticoid receptor only and not the mineralocorticoid receptor. These drugs are widely used in therapy of inflammatory and autoimmune diseases [19, 20].
The general therapeutic effects in different organs of the body and side efffects of glucocorticoid are shown in Fig. 22.2.
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Fig. 22.2
Therapeutic and side effects of glucocorticoid

Dose and Route of Administration of Corticosteroids in Endophthalmitis

Intravitreal Route

Dexamethasone is the most common steroids administered intravitreally. Intravitreal dexamethasone has been proven nontoxic in rabbits up to 400 μg, but there is no precise minimum dose for the therapeutic effect, and even the smallest dose has some beneficial effect [21]. In a prospective randomized trial, it was reported to reduce inflammation faster both in culture-positive and culture-negative endophthalmitis and did not affect the final visual outcome [22]. It is advisable to inject intravitreal steroids separately and not with other antibiotics, particularly vancomycin, since precipitation of the drug is known to occur.

Topical

Topical steroids have the potential to penetrate an intact cornea and its efficacy is proportional to the frequency of instillation [23].

Systemic Route

It is a general practice to withhold the administration of systemic steroids until the culture reports are available and specific antibiotics are administered for at least 24 h. The recommended dose is 1.0–1.5 mg/kg/day of oral prednisolone administered in two to three divided doses to achieve uniform concentration throughout the day [23].
While most ophthalmologists agree that steroids have a potentially beneficial role in bacterial endophthalmitis, the choice of the route of administration is not uniform with most controversies persisting in regard to the intravitreal steroid therapy.

Timing of Intravitreal Steroid Injection

The combination therapy of antibiotic and dexamethasone given between 24 and 72 h after inoculation reduced inflammation in Staphylococcus aureus endophthalmitis in rabbits [24, 25], though it did not work in experimental Pseudomonas endophthalmitis when the combination therapy was given 6 h after the inoculation [21, 26]. While there are multiple studies indicating the timing of the first corticosteroid intravitreal injection, there is no study on the effect of repeated intravitreal corticosteroids in endophthalmitis.

Choice of Corticosteroids

Triamcinolone Acetonide

Triamcinolone is a synthetic corticosteroid (Fig. 22.3) and is eight times more potent than prednisolone. Triamcinolone seems to contain inflammation in experimental Staphylococcus endophthalmitis [27, 28]. Safety and efficacy have been shown in human studies [5, 29] when given after the sensitive intravitreal antibiotic injection. Triamcinolone acetonide is a suspension; it is given at a dose of 4 mg in 0.1 ml, and the clearance time in rabbit is faster in vitrectomized eyes (1.57 day in vitrectomized eyes and 2.89 in non-vitrectomized eyes) [30].
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Fig. 22.3
Structure of triamcinolone acetonide

Dexamethasone Sodium Phosphate

Dexamethasone sodium phosphate (Fig. 22.4) is a clear solution. The intravitreal dose is 0.4 mg in 0.1 ml, and its half-life is quite short. While in a prospective human study involving 63 patients Das et al. [22] have shown quick reduction in inflammation without affecting the final vision at 3 months, Shah et al. [7] in a retrospective study involving 57 patients reported less likelihood of three lines of improvement in eyes that received intravitreal dexamethasone as part of endophthalmitis management [7]. Subsequent studies by Gan et al. [31] and Albrecht et al. [32] did not report any adverse impact of intravitreal dexamethasone adjuvant therapy on the final visual outcome in human eyes.
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Fig. 22.4
Structure of dexamethasone
Intravitreal corticosteroids are not advocated in fungal endophthalmitis. Majji et al. [33] did not report any detrimental effect of intravitreal dexamethasone given to eyes as part of a larger prospective study; in fact, the number of patients with favourable visual outcome was greater in the corticosteroid group. In an experimental study, Candida albicans endophthalmitis, when treated with a combination of amphotericin B and dexamethasone intravitreal injection, resulted in clearer vitreous and did not compromise the antifungal effect of amphotericin B [34].
The clinical and experimental studies of intravitreal corticosteroid are shown in Tables 22.1 and 22.2.
Table 22.1
Studies involving intravitreal corticosteroids in endophthalmitis in human subjects
Author
Intravitreal steroid
Organism
Result
Das et al. [22]
Dexamethasone
Bacteria
Early reduction of inflammation but no change in final visual outcome in steroid-antibiotic combination group
Shah et al. [7]
Dexamethasone
Bacteria
Reduced likelihood of obtaining a three-line improvement in visual acuity in steroid-antibiotic combination group vs. antibiotic alone group
Gan et al. [31]
Dexamethasone
Bacteria
Better visual outcome in steroid-antibiotic combination group vs. placebo and antibiotic
Albrecht et al. [32]
Dexamethasone
Bacteria
Steroid group had better visual acuity compared to the placebo, but this was not statistically significant
Majji et al. [33]
Dexamethasone
Fungi
Favourable visual outcome was greater in the steroid antifungal combination group, but this was not statistically significant
Flak et al. [29]
Triamcinolone acetate
Bacteria
Favourable outcome in steroid-antibiotic combination group
Pathengay et al. [5]
Triamcinolone acetate
Bacteria
Reduced inflammation in steroid-antibiotic combination group
Table 22.2
Studies involving intravitreal corticosteroids in experimental endophthalmitis in rabbits
Author
Intravitreal steroid
Organism
Result
Yoshizumi et al. [24]
Dexamethasone
Staphylococcus aureus
Group treated with steroid-antibiotic combination showed better ERG response and less inflammation
Ermis et al. [35]
Dexamethasone
Staphylococcus aureus
Difference in the histopathological scores between the treated groups was not statistically significant
Meredith et al. [36]
Dexamethasone
Staphylococcus aureus
Group treated with intraocular steroids showed increased inflammatory scores, choroidal inflammation and retinal necrosis
De Kaspar et al. [25]
Dexamethasone
Staphylococcus aureus
Group treated with steroid-antibiotic combination showed better ERG response and less clinical and histological inflammation
Yildirim et al. [37]
Dexamethasone
Staphylococcus epidermidis
Lower histopathological scores in treated groups vs. control groups
Smith et al. [8]
Dexamethasone
Staphylococcus epidermidis
Less histological inflammation in group treated with steroid-antibiotic combination
Meredith et al. [38]
Dexamethasone
Staphylococcus epidermidis
Quantitative grading of inflammation and media clarity was least in the group treated with vitrectomy, intraocular antibiotics and steroids
Ermis et al. [39]
Dexamethasone
Staphylococcus epidermidis
Difference in the histopathological scores between the treated groups was not statistically significant
Park et al. [2]
Dexamethasone
Streptococcus pneumoniae
Significant reduction in intraocular inflammation in the steroid-antibiotic combination treated group
Liu et al. [40]
Dexamethasone
Bacillus cereus
Significant decreased inflammation in the retina was seen in the steroid-antibiotic combination group
Liu et al. [40]

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Mar 1, 2018 | Posted by in OPHTHALMOLOGY | Comments Off on Corticosteroids in Endophthalmitis

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