In vitro drug-induced spoliation of a keratoprosthetic hydrogel

Traian V. Chirila, David A. Morrison, Celia R. Hicks, Zoya Gridneva, Christopher J. Barry, Sarojini Vijayasekaran

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose: To investigate in vitro the effects of selected drugs on the spoliation of poly(2-hydroxyethyl methacrylate) (PHEMA), a synthetic acrylic hydrogel currently used for the manufacture of a keratoprosthesis, AlphaCor TM. The experiments were carried out both in the presence of simulated aqueous humor (SAH) and in its absence. Methods: Disks of PHEMA were incubated and shaken with 9 commonly prescribed drugs at 37°C in sterile conditions for 1 week. Samples were incubated either in SAH only (controls), in each drug preparation, or in each drug for 1 week followed by 1 week in SAH. The drugs selected for this study were steroids (prednisolone, dexamethasone, fluorometholone, medroxyprogesterone), antiglaucoma drugs (timolol maleate and pilocarpine), and antibiotics (chloramphenicol, cephazolin, and ciprofloxacin), as commercially available formulations. Following incubation, the PHEMA specimens were examined visually and then histologically, after staining with alizarin red for the presence of calcium in the spoliating sediments/deposits. Results: Although only 5 of the drug formulations (dexamethasone as Maxidex, fluorometholone as FML, pilocarpine as Isopto Carpine, chloramphenicol as Chlorsig, and medroxyprogesterone as Depo-Ralovera) induced spoliation of the hydrogel in the absence of SAH, all drugs induced spoliation after postincubation in SAH, and calcium was detected in the majority of samples. The deposits on the hydrogel specimens incubated first in cephazolin (as Cefazolin-BC), pilocarpine (as Isopto Carpine), and chloramphenicol (as Chlorsig) and then in SAH did not contain calcium, despite its presence in SAH. Conclusions: The study appears to confirm our earlier clinical observations that topical medication may play a role in the spoliation of the hydrogel opthalmic devices. Presence of calcium in the deposits seems to be correlated to the nature of drug. Although the incidence of spoliation in real clinical situations is much lower than suggested by this extreme-case in vitro simulation, topical therapy after implantation of AlphaCor TM should be carefully considered, kept to the minimum required, and additive-free where possible.

Original languageEnglish
Pages (from-to)620-629
Number of pages10
JournalCornea
Volume23
Issue number6
DOIs
Publication statusPublished - Aug 2004

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Aqueous Humor
Hydrogel
Fluorometholone
Cefazolin
Pilocarpine
Pharmaceutical Preparations
Chloramphenicol
Medroxyprogesterone
Dexamethasone
Calcium
Drug Compounding
Timolol
Ciprofloxacin
Prednisolone
In Vitro Techniques
Steroids
Staining and Labeling
Anti-Bacterial Agents
Equipment and Supplies
Incidence

Cite this

Chirila, Traian V. ; Morrison, David A. ; Hicks, Celia R. ; Gridneva, Zoya ; Barry, Christopher J. ; Vijayasekaran, Sarojini. / In vitro drug-induced spoliation of a keratoprosthetic hydrogel. In: Cornea. 2004 ; Vol. 23, No. 6. pp. 620-629.
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title = "In vitro drug-induced spoliation of a keratoprosthetic hydrogel",
abstract = "Purpose: To investigate in vitro the effects of selected drugs on the spoliation of poly(2-hydroxyethyl methacrylate) (PHEMA), a synthetic acrylic hydrogel currently used for the manufacture of a keratoprosthesis, AlphaCor TM. The experiments were carried out both in the presence of simulated aqueous humor (SAH) and in its absence. Methods: Disks of PHEMA were incubated and shaken with 9 commonly prescribed drugs at 37°C in sterile conditions for 1 week. Samples were incubated either in SAH only (controls), in each drug preparation, or in each drug for 1 week followed by 1 week in SAH. The drugs selected for this study were steroids (prednisolone, dexamethasone, fluorometholone, medroxyprogesterone), antiglaucoma drugs (timolol maleate and pilocarpine), and antibiotics (chloramphenicol, cephazolin, and ciprofloxacin), as commercially available formulations. Following incubation, the PHEMA specimens were examined visually and then histologically, after staining with alizarin red for the presence of calcium in the spoliating sediments/deposits. Results: Although only 5 of the drug formulations (dexamethasone as Maxidex, fluorometholone as FML, pilocarpine as Isopto Carpine, chloramphenicol as Chlorsig, and medroxyprogesterone as Depo-Ralovera) induced spoliation of the hydrogel in the absence of SAH, all drugs induced spoliation after postincubation in SAH, and calcium was detected in the majority of samples. The deposits on the hydrogel specimens incubated first in cephazolin (as Cefazolin-BC), pilocarpine (as Isopto Carpine), and chloramphenicol (as Chlorsig) and then in SAH did not contain calcium, despite its presence in SAH. Conclusions: The study appears to confirm our earlier clinical observations that topical medication may play a role in the spoliation of the hydrogel opthalmic devices. Presence of calcium in the deposits seems to be correlated to the nature of drug. Although the incidence of spoliation in real clinical situations is much lower than suggested by this extreme-case in vitro simulation, topical therapy after implantation of AlphaCor TM should be carefully considered, kept to the minimum required, and additive-free where possible.",
keywords = "Calcification, Hydrogels, Intraocular implants, Keratoprosthesis, Simulated aqueous humor, Spoliation, Topical medication",
author = "Chirila, {Traian V.} and Morrison, {David A.} and Hicks, {Celia R.} and Zoya Gridneva and Barry, {Christopher J.} and Sarojini Vijayasekaran",
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Chirila, TV, Morrison, DA, Hicks, CR, Gridneva, Z, Barry, CJ & Vijayasekaran, S 2004, 'In vitro drug-induced spoliation of a keratoprosthetic hydrogel' Cornea, vol. 23, no. 6, pp. 620-629. https://doi.org/10.1097/01.ico.0000121703.74077.ea

In vitro drug-induced spoliation of a keratoprosthetic hydrogel. / Chirila, Traian V.; Morrison, David A.; Hicks, Celia R.; Gridneva, Zoya; Barry, Christopher J.; Vijayasekaran, Sarojini.

In: Cornea, Vol. 23, No. 6, 08.2004, p. 620-629.

Research output: Contribution to journalArticle

TY - JOUR

T1 - In vitro drug-induced spoliation of a keratoprosthetic hydrogel

AU - Chirila, Traian V.

AU - Morrison, David A.

AU - Hicks, Celia R.

AU - Gridneva, Zoya

AU - Barry, Christopher J.

AU - Vijayasekaran, Sarojini

PY - 2004/8

Y1 - 2004/8

N2 - Purpose: To investigate in vitro the effects of selected drugs on the spoliation of poly(2-hydroxyethyl methacrylate) (PHEMA), a synthetic acrylic hydrogel currently used for the manufacture of a keratoprosthesis, AlphaCor TM. The experiments were carried out both in the presence of simulated aqueous humor (SAH) and in its absence. Methods: Disks of PHEMA were incubated and shaken with 9 commonly prescribed drugs at 37°C in sterile conditions for 1 week. Samples were incubated either in SAH only (controls), in each drug preparation, or in each drug for 1 week followed by 1 week in SAH. The drugs selected for this study were steroids (prednisolone, dexamethasone, fluorometholone, medroxyprogesterone), antiglaucoma drugs (timolol maleate and pilocarpine), and antibiotics (chloramphenicol, cephazolin, and ciprofloxacin), as commercially available formulations. Following incubation, the PHEMA specimens were examined visually and then histologically, after staining with alizarin red for the presence of calcium in the spoliating sediments/deposits. Results: Although only 5 of the drug formulations (dexamethasone as Maxidex, fluorometholone as FML, pilocarpine as Isopto Carpine, chloramphenicol as Chlorsig, and medroxyprogesterone as Depo-Ralovera) induced spoliation of the hydrogel in the absence of SAH, all drugs induced spoliation after postincubation in SAH, and calcium was detected in the majority of samples. The deposits on the hydrogel specimens incubated first in cephazolin (as Cefazolin-BC), pilocarpine (as Isopto Carpine), and chloramphenicol (as Chlorsig) and then in SAH did not contain calcium, despite its presence in SAH. Conclusions: The study appears to confirm our earlier clinical observations that topical medication may play a role in the spoliation of the hydrogel opthalmic devices. Presence of calcium in the deposits seems to be correlated to the nature of drug. Although the incidence of spoliation in real clinical situations is much lower than suggested by this extreme-case in vitro simulation, topical therapy after implantation of AlphaCor TM should be carefully considered, kept to the minimum required, and additive-free where possible.

AB - Purpose: To investigate in vitro the effects of selected drugs on the spoliation of poly(2-hydroxyethyl methacrylate) (PHEMA), a synthetic acrylic hydrogel currently used for the manufacture of a keratoprosthesis, AlphaCor TM. The experiments were carried out both in the presence of simulated aqueous humor (SAH) and in its absence. Methods: Disks of PHEMA were incubated and shaken with 9 commonly prescribed drugs at 37°C in sterile conditions for 1 week. Samples were incubated either in SAH only (controls), in each drug preparation, or in each drug for 1 week followed by 1 week in SAH. The drugs selected for this study were steroids (prednisolone, dexamethasone, fluorometholone, medroxyprogesterone), antiglaucoma drugs (timolol maleate and pilocarpine), and antibiotics (chloramphenicol, cephazolin, and ciprofloxacin), as commercially available formulations. Following incubation, the PHEMA specimens were examined visually and then histologically, after staining with alizarin red for the presence of calcium in the spoliating sediments/deposits. Results: Although only 5 of the drug formulations (dexamethasone as Maxidex, fluorometholone as FML, pilocarpine as Isopto Carpine, chloramphenicol as Chlorsig, and medroxyprogesterone as Depo-Ralovera) induced spoliation of the hydrogel in the absence of SAH, all drugs induced spoliation after postincubation in SAH, and calcium was detected in the majority of samples. The deposits on the hydrogel specimens incubated first in cephazolin (as Cefazolin-BC), pilocarpine (as Isopto Carpine), and chloramphenicol (as Chlorsig) and then in SAH did not contain calcium, despite its presence in SAH. Conclusions: The study appears to confirm our earlier clinical observations that topical medication may play a role in the spoliation of the hydrogel opthalmic devices. Presence of calcium in the deposits seems to be correlated to the nature of drug. Although the incidence of spoliation in real clinical situations is much lower than suggested by this extreme-case in vitro simulation, topical therapy after implantation of AlphaCor TM should be carefully considered, kept to the minimum required, and additive-free where possible.

KW - Calcification

KW - Hydrogels

KW - Intraocular implants

KW - Keratoprosthesis

KW - Simulated aqueous humor

KW - Spoliation

KW - Topical medication

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DO - 10.1097/01.ico.0000121703.74077.ea

M3 - Article

VL - 23

SP - 620

EP - 629

JO - Cornea

JF - Cornea

SN - 0277-3740

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