Deep Corneal Calcification Associated With Preservative-free Eyedrops and Persistent Epithelial Defects

Lake, Damian; Tarn, Anne; Ayliffe, William

doi:10.1097/ico.0b013e31815c5a24

Cited by 23 publications

(13 citation statements)

References 12 publications

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“…Several previous studies have reported that calcium deposition is associated with chronic epithelial defects (Lake et al. 2008), inflammation (López‐Mejías & González‐Gay 2019), dry eye (Lemp & Ralph 1977; Jhanji et al. 2011) and topical phosphate‐containing eyedrop therapy (Taravella et al.…”

Section: Discussionmentioning

confidence: 99%

Corneal calcification of acellular porcine corneal stroma following lamellar keratoplasty

Dong

Zhou

et al. 2020

Acta Ophthalmologica

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Purpose: To describe the corneal calcification of acellular porcine corneal stroma (APCS) following lamellar keratoplasty (LKP) and identify risk factors. Methods: Two cases of APCS calcification were evaluated by slit-lamp photography and anterior segment optical coherence tomography (AS-OCT). von Kossa staining and scanning electron microscope/energy-dispersive spectrometry (SEM/EDS) were performed on pathologic tissue. Associated graft and postoperative risk factors were analysed. Acellular porcine corneal stroma (APCS) cleanliness and element content after rinsing with sterilized water were observed by SEM/EDS and inductively coupled plasma mass spectrometry. Calcium metabolism-related proteins were analysed by protein mass spectrometry. Corneal epithelial defects and postoperative medications were reviewed. Results: Two cases of APCS calcification occurred at 23 and 22 days postoperatively. Anterior segment optical coherence tomography (AS-OCT) and von Kossa staining demonstrated calcium deposition in the superficial stroma composed of calcium, phosphorus and oxygen conforming to the Ca/P ratio of hydroxyapatite. Phosphate crystals were present on the APCS surface and decreased with number of rinsing times. The phosphorus content of APCS was minimal after rinsing 10 times and avoiding excessive corneal swelling. Calcium metabolism-related proteins were downregulated in APCS. Patients with corneal calcification had 1-week postoperative corneal epithelial defects and were treated with three types of phosphorous eyedrops. Conclusions: Acellular porcine corneal stroma (APCS) calcification occurs in the superficial corneal stroma about 1 month after LKP. The application of AS-OCT, von Kossa staining and SEM/EDS provides a basis for the clinical and pathological diagnosis of corneal calcification. The associated risk factors were mainly high phosphorus content and downregulated calcium metabolism-related proteins in APCS. Postoperative epithelial defects, inflammation and use of phosphorous eyedrops may promote corneal calcification.

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Section: Discussionmentioning

confidence: 99%

Corneal calcification of acellular porcine corneal stroma following lamellar keratoplasty

Dong

Zhou

et al. 2020

Acta Ophthalmologica

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“…16 In cases with both epithelial damage and disruption of Bowman’s membrane, accumulation occurs in the deeper corneal stroma and Descemet’s membrane in the form of calcareous degeneration. 17 The solubility of these crystals decreases with alkaline pH and high temperature. 18 The pH value (physiological range 7.6-7.8) 19 and tonicity of the ocular surface, extent of epithelial damage, and presence of inflammation and barrier dysfunction are among the factors responsible for the development of corneal calcification.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Phosphate and Osmolarity Levels in Chronically Administered Eye Drops

Özalp

Atalay

Kebapçı

et al. 2019

tjo

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Objectives: To assess phosphate and osmolarity levels of chronically administered eye drops commercially available in Turkey. Materials and Methods: A total of 53 topical eye drops including 18 antiglaucoma drugs, 4 nonsteroidal anti-inflammatory drugs (NSAIDs), 10 corticosteroids, 7 antihistaminics, and 14 artificial tears identified using the Vademecum Modern Medications Guideline (2018) were included in the study. Phosphate levels were assessed using Roche Cobas C501 analyzer (Roche Diagnostics GmbH, Mannheim, Germany) and the respective kits. Osmolarity was assessed using Vescor Vapro 5600 vapor pressure osmometer (Sanova Medical Systems, Vienna, Austria). Mean phosphate and osmolarity levels were obtained after averaging three measurements. Eye drops were categorized as isoosmolar, hypoosmolar and hyperosmolar based on physiologic tear osmolarity range (296.5±9.8 mOsm/L). Results: The highest phosphate concentration was found in the antiglaucoma group (20.3±35.4 mmol/L), followed by antihistaminics (17.3±17.9 mmol/L), corticosteroids (15.2±19.1 mmol/L), artificial tears (0.8±1.0), and NSAIDs (0.04±0.08). Percentage of medications in the hyperosmolar category was highest in the NSAI group (75%), followed by antihistaminics (43%), corticosteroids (20%), and antiglaucoma drugs (19%). Nearly all of the artificial tear formulations were in the hypoosmolar (71%) or isoosmolar (21%) categories. Conclusion: Approximately 40% of glaucoma medications and approximately 60% of corticosteroid and antihistaminic medications had a phosphate concentration higher than the physiologic tear phosphate level (1.45 mmol/L).

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“…Intact epithelium and absence of Bowman layer in the presence of high level of phosphate ions plus an inflammatory response seem to provide the necessary environment for the formation of calcium salts deep within the stroma of the cornea (37,45). Reports have implicated the role of sodium hyaluronate artificial tears, preservatives of eyedrops with phosphate buffers, timolol, retinoic acid and dexamethasone in calcium salt depositions (36,41,42).…”

Section: Corneal Calcification and Treatment With Amniotic Membrane Tmentioning

confidence: 99%

“…Reports have implicated the role of sodium hyaluronate artificial tears, preservatives of eyedrops with phosphate buffers, timolol, retinoic acid and dexamethasone in calcium salt depositions (36,41,42). Calcium salt deposition can also occur in cases of older patients, decreased tear production, and history with previous herpes virus infection (37,45). The high phosphate concentration leads to a critical increase of the calcium phosphate which together with the breakdown of the tissue barrier, results in the formation of hydroxyapatite deposits (36).…”

Section: Corneal Calcification and Treatment With Amniotic Membrane Tmentioning

confidence: 99%

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Ultrasound biomicroscopy as a diagnostic method of corneal degeneration and inflammation

Skribek

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Deep Corneal Calcification Associated With Preservative-free Eyedrops and Persistent Epithelial Defects

Abstract: A contributory factor in our case series seems to be the use of preservative-free medications in persistent epithelial defects. The preservative-free medications we measured had high levels of phosphate, which may not be common knowledge.

Cited by 23 publications

References 12 publications

Corneal calcification of acellular porcine corneal stroma following lamellar keratoplasty

Corneal calcification of acellular porcine corneal stroma following lamellar keratoplasty

Assessment of Phosphate and Osmolarity Levels in Chronically Administered Eye Drops

Ultrasound biomicroscopy as a diagnostic method of corneal degeneration and inflammation

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