Identifying and treating amiodarone-induced corneal deposits: When the heart saves and the cornea speaks

Table 1 Key studies included in the literature review

Ref.	Study design	Sample size	Main findings reported in the literature	Clinical relevance
Chew et al[16]	Clinical series	37 patients	In an early clinical series, typical amiodarone keratopathy was documented in 35 of 37 treated patients, although none reported ocular symptoms. In the patient who underwent corneal biopsy because of severe keratopathy, electron microscopy showed membrane-bound lamellar bodies throughout the corneal epithelium, along with predominantly granular membrane-bound structures in stromal keratocytes	This study supports the view that amiodarone keratopathy is common, often clinically silent, and ultrastructurally consistent with intracellular drug-related deposition
Alnawaiseh et al[17]	Comparative observational study	66 consecutively enrolled amiodarone-treated patients vs 66 healthy controls	Scheimpflug corneal densitometry demonstrated significantly higher corneal light backscatter in patients receiving amiodarone than in healthy controls. N-desethylamiodarone levels showed the strongest correlation with anterior corneal densitometry, whereas treatment duration and cumulative dose were associated with full-thickness densitometric changes	These findings suggest that corneal densitometry may provide an objective tool for quantifying and monitoring corneal involvement during amiodarone therapy
Rivera et al[18]	Case report	1 patient	A grade IV amiodarone-induced keratopathy was described in a soft contact lens wearer. Among 686 amiodarone-treated patients followed at the Mayo Clinic, this was the first grade IV case identified	This report indicates that advanced keratopathy can occur, but appears to be distinctly rare
Frings and Schargus[19]	Case report	1 patient	In a single case, topical treatment with unpreserved phosphate-free 01% sodium hyaluronate containing heparin was associated with a marked reduction in the area of cornea verticillata and with improvement in keratopathy grade over 3 months, whereas the fellow eye treated with sodium hyaluronate alone showed no comparable change	This observation suggests that, at least in selected cases, corneal deposits may partially regress with topical treatment
Mehta et al[20]	Case report	1 patient	Complete disappearance of cornea verticillata was documented during ongoing amiodarone therapy after rifampin reduced serum amiodarone and desethylamiodarone concentrations to subtherapeutic levels. The deposits reappeared after rifampin discontinuation, once therapeutic drug levels were restored	This case strongly supports the idea that corneal deposits reflect dynamic systemic exposure rather than fixed, irreversible corneal damage
Inoue et al[21]	Case report	1 patient	In a patient with epithelial basement membrane dystrophy, typical vortex opacities coexisted with oval-shaped corneal lesions. In vivo confocal microscopy revealed highly reflective epithelial cell clusters, epithelial basement membrane abnormalities, and epithelial microcysts	This report shows that amiodarone keratopathy may assume atypical morphologic features when the epithelial microenvironment is altered
Rogers et al[22]	Case report	1 patient	In a grafted cornea, the whorl-like pattern of amiodarone keratopathy was oriented almost 90 degrees from its usual direction	This case suggests that local corneal architecture or epithelial migratory behavior may influence the visible orientation of vortex deposits
Bhatt and Ramaesh[23]	Case report	1 patient	An unusual unilateral presentation was described in a patient taking amiodarone whose fellow eye, fitted with an occlusive contact lens, remained free of keratopathy. Reduced ultraviolet exposure was proposed as a possible explanation	This observation highlights that asymmetrical or unilateral presentations may occur under specific local surface conditions
Erdurmus et al[24]	Case report	1 patient	Confocal laser scanning microscopy demonstrated not only epithelial verticillata, but also reflective deposits around stromal keratocytes and diffuse bright microdeposits within endothelial cells	This case indicates that, although amiodarone keratopathy is usually considered an epithelial process, deeper corneal involvement may occasionally be present
Meng et al[25]	Case report and literature review	1 patient	A patient developed both corneal deposits and optic neuropathy during systemic amiodarone treatment. The accompanying review emphasized that keratopathy is generally benign and potentially reversible, whereas optic neuropathy is rare but may lead to permanent visual loss	This report reinforces the need to reconsider the diagnosis whenever visual loss appears disproportionate to the corneal findings alone