Intracameral dexamethasone injection in the treatment of cataract surgery induced inflammation: design, development, and place in therapy

Figures & data

Figure 1 A model of the mechanism of action upon administration of intraocular DXM.

Notes: The steroid traverses the cellular membrane as a free molecule and interacts with glucocorticoid-receptor. The dimerized complex enters the nucleus where it acts as a transcription factor to upregulate and downregulate certain products to promote its anti-inflammatory effects. Additionally, free DXM inhibits the production of prostaglandins, which are implicated in post-surgical ocular symptoms.
Abbreviations: DXM, dexamethasone; CBG, cortisol-binding globulin; GR, glucocorticoid receptor; HSP, heat-shock protein; IL-1RA, interleukin-1 receptor antagonist; IL-10, interleukin 10; IL-1, interleukin-1; IL-1b, interleukin-1b; Cxcl-10, chemokine (C-X-C motif) ligand; TNF-α, tumor necrosis factor α; COX-1, cyclooxygenase 1; COX-2, cycloxygenase 2.

Table 1 A summary of the advantages and disadvantages of various routes of DXM delivery to control post-cataract surgery inflammation

Possible routes of DXM delivery to control inflammation after cataract surgery
Route	Delivery area	Advantages	Disadvantages
Topical	Cornea, sclera, conjunctiva	• Noninvasive • Greatest evidence of efficacy and safety • Easier on surgeon • Higher patient preference • Self-administrable • Many formulations (eg, prodrugs, nanotechnology, cubosomes, etc.) available to increase bioavailability	• Low patient compliance • Low bioavailability • Away from target site → greater amount needed
Periocular	Transscleral (subconjunctival, sub-tenon, etc.)	• Not as painful as other injections • Higher therapeutic drug levels • Closer to target area • Bypasses corneal barrier	• Greater risk of skin hypopigmentation, subdermal fat atrophy, extraocular muscle atrophy • Higher risk for systemic side effects • Tissue hemorrhage
Intracameral	Anterior chamber or posterior chamber	• More direct method • Lesser drug amount needed • Reduces corneal and systemic side effects seen with topical steroid application • Bypasses corneal barrier	• Invasive • Risk of toxic anterior segment syndrome • Risk of toxic endothelial cell destruction syndrome • Tissue hemorrhage
Intravitreal	Vitreous	• Bypasses blood–retinal barrier • Bypasses corneal barrier • Beneficial in preventing worsening of diabetic macular edema	• Serious side effects may occur with repeat injections, such as endophthalmitis and retinal detachment • Invasive
Systemic	Oral/intramuscular/intravitreal	• Higher patient compliance • Easier on surgeon	• Low bioavailability • Higher doses required leading to greater likelihood of toxicity • Needs to bypass blood-aqueous and blood-retinal barrier

Abbreviation: DXM, dexamethasone.

Table 2 A summary of the visual acuity using intracameral DXM and topical steroids at a postoperative interval (~4–6 weeks). Only studies that quantitatively evaluated visual acuity using the logMAR scale were included

Postoperative LogMAR after intracameral DXM vs topical steroid
Study	LogMAR	Total eyes, n
Gungor et al, 2014^Citation20 (intracameral)	0.07±NA*	30
Wadood et al, 2004^Citation19 (intracameral)	0.06±0.0	11
Wadood et al, 2004^Citation19 (topical)	0.15±0.2	8
Asano et al, 2008^Citation71 (topical)	−0.066±0.078	52
Endo et al, 2010^Citation72 (topical)	−0.04±0.085	31
Miyanaga et al, 2009^Citation73 (topical)	0.07±0.08	22
Wang et al, 2013^Citation74 (topical)	0.084±0.1	43

Notes:

* Indicates that no standard deviation was reported in this study. Topical steroid use varied between studies. Notably, Gungor 2014 (Intracameral) cohort also received postoperative prednisone acetate drops as part of their standard of care. Wadood 2003 (Intracameral) cohort did not receive any postoperative steroid drops.

Abbreviations: DXM, dexamethasone; NA, not available.

Table 3 A summary of evidence of all studies that have used intracameral DXM after cataract surgery

Summary of evidence of intracameral DXM use after cataract surgery
Study	Delivery method	Anterior cell and flare	Visual symptoms	IOP	Corneal endothelial cells	Significant adverse events
Tan et al 1999^Citation16	Surodex^®	Lower scores compared to topical group at all postoperative visits	Less early postop ocular discomfort & tearing than topical group	2 cases of IOP spikes on day 15	No difference compared to topical group	Trauma-related iris prolapse
Chang et al 1999^Citation17	Surodex^® (Phase II)	Lower scores compared to no treatment group	Less ocular discomfort, pain, photophobia & lacrimation than no treatment group	N/A	No difference compared to no treatment group	Persistent wound leakage
Tan et al 2001^Citation18	Surodex^®	No difference compared to topical group	Less ocular discomfort, photophobia & lacrimation than topical group	N/A	No difference compared to topical group	Localized angle changes from
Wadood et al 2004^Citation19	Surodex^®	No difference compared to topical group	No difference when compared to topical group	No difference compared to topical group	No difference compared to topical group	None
Chang et al 2009^Citation67	0.4 mg/0.1 mL injection	Lower scores compared to no treatment group	Less ocular discomfort, photophobia & lacrimation than no treatment group	No significant difference compared to no treatment group	N/A	None
Gungor et al 2014^Citation20	0.4 mg/0.1 mL injection	No difference compared to intracameral triamcinolone acetonide use	No difference compared to intracameral triamcinolone acetonide use	Less IOP increase in first 24 hours than triamcinolone acetonide	No difference compared to intracameral triamcinolone acetonide	None
Donnenfeld et al 2018^Citation22	Dexycu^® (Phase III)	Lower scores compared to no treatment group	N/A	Increase in IOP more than no treatment group	N/A	None

Notes: Studies that did not report either subjective visual symptoms, anterior cell and flare score, intraocular pressure, or corneal endothelial cell count after surgery were not included.

Abbreviations: DXM, dexamethasone; IOP, intraocular pressure; N/A, not available.

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