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Therapeutic contact lenses and eyedrops — is there a problem?
Contact Lens and Anterior Eye, Vol. 20, No. 1, pp. 9-11, 1997
© 1997 British Contact Lens Association
Printed in Great Britain
THERAPEUTIC CONTACT LENSES AND EYEDROPS A PROBLEM?
IS THERE
Martin P. Rubinstein* and Jane E. Evanst (Received 8th July 1996; in revised form 25th October 1996)
Abstract-- Numerous authors have investigated the interactions of contact lenses with their care solutions. Many reported hypersensitivity and toxicity reactions induced by the preservative in the care solution, especially with soft contact lenses. In medical contact lens practice the concurrent use of eyedrops in a patient wearing therapeutic contact lenses is a contentious issue. The usual practice is to prescribe unpreserved drops. In reviewing the literature, we found no evidence of complications using preserved eyedrops with such contact lenses in situ. The reluctance to prescribe preserved topical medication could stem from the evidence relating to contact lens care solutions. KEY WORDS:
Preservatives, benzalkonium chloride, chlorhexidine gIuconate, thiomersal, contact lenses, toxicity, eyedrops
Introduction
p
reservatives used in topical ophthalmic preparations can result in a wide variety of toxicity or hypersensitivity reactions. ~,2 The use of eyedrops in patients wearing therapeutic contact lenses is therefore a contentious issue. In one of the major contemporary contact lens texts advice is both confusing and contradictory. 3,4 The British National Formulary and the Monthly Index of Medical Specialities advise discontinuation of contact lens wear (particularly soft lenses) when using preserved preparations. Unpreserved drops are suggested as a safer alternative? There appears to be less concern regarding wearers of rigid gas-permeable lenses. This issue is of particular importance in medical contact lens practice where therapeutic lenses are widely used for specific purposes and often for periods exceeding 24h. In these circumstances, unpreserved drops are frequently prescribed, at considerably greater cost than their preserved equivalent. This perceived problem of using preserved eyedrops with contact lenses may stem from previous studies of contact lens interactions with care solutions. Contact Lens Interactions with Care S o l u t i o n s There is extensive literature describing the adverse ocular effects of preservatives in contact lens care solutions. The active ingredients and preservatives in contact lens care solutions may bind to and impregnate the constituent polymer and be retained for long periods of time. Soft Lenses
Gasset 6 reported a toxicity reaction in a unilateral aphakic soft lens wearer. On changing from an unpreserved to a preserved care regimen, after 3 days the eye became inflamed. This was attributed to the cytoxic effects of benzalkonium chloride (BAK) in the care * FCOptom PhD. t MCOptom, MPhil.
system used. BAK, a cationic preservative, has been shown to be a strong strong soft lens binder, indicating the influence of electrostatic forces. 3 Other authors have confirmed this effectJ ,8 High water content lenses absorb greater quantifies of BAK than do low water content lenses) Chlorhexidine gluconate (CLX), is also a weak cationic preservative. CLX in cleaning solutions has also been shown to accumulate in soft lenses. 1° It has a large molecular structure, hence its binding capacity is about one tenth of that of BAI~ However, CLX is very effectively bound to protein deposits on lens surfaces, which exacerbates the binding effect. At the concentration likely to be found in the tear film, following desorpfion from soft lenses, it produces little effect on the corneal epithelium. 11 Thiomersal is an anionic preservative and binding effects with soft lenses have been considered to be much weaker. However, thiomersal keratopathy has been another well documented problem 1~,1~ although cases are infrequently seen nowadays. In the current generation of multi-function, soft lens care solutions large molecular weight preservatives are used (e.g., Polyquad, Dymed). These resist diffusion into the lens matrix hence minimising potential problems. 14,15 But a recent study advocates caution in the use of such solutions. 16 Rigid Lenses
Various authors consider that binding and toxicity effects with PMMA and RGP materials are negligible. This has been reported for BAK, 17,18thiomersaP 9 and chlorhexidine, e° Other authors are more cautious regarding BAK-containing solutions and RGP lenses31,22 Cases have been reported of kerafifis thought to have been related to BAK binding. 23 Effects of Preservatives o n the Anterior Segment
Manifestations of BAK toxicity include marked conjuncrival hyperaemia and minimal chemosis. In an animal study using rabbits, corneal signs of BAK binding were
THERAPEUTICCONTACTLENSESAND EYEDROPS- - IS THEREA PROBLEM?
reported as superficial puntate epitheliopathy and filamentary keratitis. 24There has been a report of destructive change to corneal stromal cells by BAK in the presence of epithelial breaks. 2~With thiomersal, similar conjunctival signs have been reported along with mild superior limbitis and cystic changes in this area progressing with increased severity of reaction to diffuse epithelial keratitisY ,13In the longer term a vascularised pannus may develop in this areaY ,13.
Contact Lenses and Eyedrops Ophthalmologists and other hospital-based clinicians generally consider it unsafe to use preserved topical medication with therapeutic soft contact lenses in situ. Extended wear of soft lenses would theoretically pose a greater risk for toxicity reactions. However, several studies of bandage lens use with topical medication find no evidence of corneal damage. In the management of severe keratoconjunctivitis sicca and filamentary keratifis with 38% water content lenses, frequent administration of artificial tears preserved with 0.01% BAK caused no adverse effects over periods of wear of up to 8 weeks. 26 Other authors found similar resultsY In the treatment of bullous keratopathy with low and high water content lenses, various types of topical medication were used including steroids, lubricants, antibiotics and those for glaucoma. The lens replacement interval varied between 1.2 to 8.3 months. Another study reported the fitting of bandage lenses (high and medium water content and silicone) for short-term use. A wide variety of ocular conditions was treated with a large range of drops. No evidence of drug-related complications was found. % Similar conclusions have been drawn in users of daily wear soft lenses. In a study of the management of giant papillary conjunctivitis it was concluded that there were no problems associated with the use of disodium cromoglycate in soft lens wearers. 29 This was further substantiated in a study showing no accumulation of either the drug (sodium cromoglycate) or its preservative (BAK) in the lenses. 3° In addition it was concluded that the preserved drop could be safely applied directly onto a worn contact lens. Although the concentration of preservative (BAK) in eyedrops is generally higher than that in contact lens care solutions, the actual contact time with the contact lens is far less. A contact lens may soak in a care solution for many hours or even days whereas a topical drop will be fairly rapidly dissipated by the action of the tears and lids. Reflex lacrimation on instillation of a drop will further enhance this effect, particularly with the more irritating drugs. Retention of preservative/drug in a hydrogel lens is theoretically proportional to water content and thickness. The general tendency is for thinner lenses, reducing any potential problems. This relationship is particularly pertinent to the use of bandage therapeutic lenses which are generally of plano power and hence very thin, even in high water content materials. The 10
potential theoretical risk of any problems will also depend on frequency of drug instillation and duration of the treatment. For example, antibiotics are frequently prescribed by ophthalmologists as an adjunct to shortterm therapeutic contact lens use. The difference in cost between equivalent volumes of preserved and unpreserved drops is highly significant - - for example in the UK a 10ml bottle of chloramphenicol currently costs 50p compared with £4.92 for 20 unit dose Minims.
Conclusion The impression from our review of the literature is that the clinical manifestations of eyedrop preservative binding with contact lenses appears to be based on anecdotal evidence, perhaps relating to contact lens care solutions. We fully accept that preservatives and indeed some active ingredients in topical ophthalmic preparations can have side effects on the anterior segment of the eye. However, in the hospital-based contact lens clinic, where therapeutic lenses are often used on a short-term basis, we question the necessity to prescribe unpreserved drops. For longer-term use of such lenses we would still advocate caution. Address for Correspondence Optometry Unit, Department of Ophthalmology, University Hospital, Nottingham NG7 2UH. REFERENCES 1Kanstd, J.J. Clinical Ophthalmology, 2nd edn, Butterworths, London, Chapter 5, 100-149 (1989). 2 O'Connor Davis, P.H., Hopkins, G.A. and Pearson, R.M. The Actions and Uses of Ophthalmic Drugs, 3rd edn, Butterworths, London, Chapter 4, 67-79 (1989). Stewart-Jones, J.H., Hopkins, G.A. and Phillips, A.J. Drugs and solutions in contact lens practice and related microbiology. In: Phillips, A.J. and Stone, J. (eds), Contact Lenses, 3rd edn, Butterworths, London, 146-148 (1989). 4 Westerhout, D. Contact lenses in abnormal conditions. In: Phillips, A.J. and Stone, J. (eds), Contact Lenses, 3rd edn, Butterworths, London, 813-814 (1989). 5 British National Formulary. British Medical Association and the Royal Pharmaceutical Society of Great Britain, 32, 430-442 (1996). 6 Gasset, A.R. BAK toxicity to the human cornea. Am. J. Ophthal., 84, 169-171 (1977). 7 Vaughan, J.S. and Porter, D.A. A new in vitro method for assessing the potential toxicity of soft contact lens care solutions. CLAO J., 19, 54-57 (1993). s Hirji, N.K., Scott, J. and Sabell, A.G. Conjuncfival Sytology in hard and soft contact lens wear. Ophthal. Physiol. Opt., 5, 333-335 (1985). 9 Chapman, J.M., Cheeks, L. and Green, K. Interactions of benzalkonium chloride with soft and hard contact lenses. Arch. Ophthal., 108, 244-246 (1990). 10Lumbroso, P., Nhamias, M., Nhamias, S. and Tranche, P. A preliminary study of the adsorption and release of preservatives by contact lenses and collagen shields. CLAOJ., 22, 61-63 (1996). n Green, IC, Livingstone, V., Bowman, K. and Hull, D. Chlorhexidine effects on corneal epithelium and endothelium. Arch. Ophthal., 98, 1273-1278 (1990). 12Wright, P. and Mackie, I. Preservative related problems in soft contact lens wearers. Trans. Ophthal. Soc. UK, 102, 3-6 (1982). 1'~Wilson-Holt, N. and Dart, J.K.D. Thiomersal keratoconjunctivitis, frequency, clinical spectrum and diagnosis. Eye, 3, 581-587 (1989). 14Lowe, R. A review of the new multi-function lens care solutions. Optician, 2 0 7 (5454), 22-25 (1994). lS Bevington, R. Evaluation of benzalkonium chloride in a soaking/disinfecting rigid gas permeable regimen. Contact Lens Spectrum, 3 (3), 30-33 (1988). 16Atkins, N. and Allsopp, G. Multi-purpose solution intolerance.
MAR?FINP. RUBINSTEINAND JANEE. EVANS Diagnosis and management. Optician, 212 (5562), 22-30 (1996). 17Bergmanson, J.P. and Barbeito, R. Clinical assessment of ocular response to a multipurpose contact lens care solution. Ophthal. Physiol. Optics, 15, 535-544 (1995). is Hoffman, W. Ending the BAK-RGP controversy. Int. Contact Lens Clinic, 14, 31-33 (1987). 19Rebert, H. and Koffel, J.C. Evaluation of thlmerosal absorption. Contactologia, 11,172-175 (1989). ~0MacKeen, D.L. and Green, K. Chlorhexidine kinetics in hard contact lenses.J. Pharm. Pharmacol., 31,714-716 (1979). 21 Rosenthal, P., Chou, M.H. Salamone, J.C. and Israel, S.C. Preservative interaction with gas permeable lenses. Optician, 192 (5071), 33-38 (1986). 22 Herskowitz R. Solution interactions and gas permeable performance. Contact Lens]., 15, 3-5 (1987). 2a Sterling, J. and Hecht, A. BAK induced chemical keratitis? Contact Lens Spectrum, 3 (3), 62-64 (1988). 24 Imayasu, M., Moriyama, T., Ichijima, H., Ohashi, J., Petroll, W.M.
Jester, J.V. and Cavanagh, H.D. The effects of daily wear of rigid gas permeable contact lenses treated with contact lens care solutions containing preservatives on the rabbit cornea. CLAO ]., 20, 183-188 (1983). 2s Collin, B. Ultrastructural changes to corneal stromal cells due to ophthalmic preservatives. Acta Ophthahnol., 64, 72-74 (1986). 28Lemp, M.A. Bandage lenses and the use of topical solutions conraining preservatives. Ann. Ophthalrnol., 10, 1319-1321 (1978). 27Andrew, N.C. and Woodward, E.G. The bandage lens in bullous keratopathy. Ophthal. Physiol. Opt., 9, 66-68 (1989). 28Smiddy, W.E., Hamburg, T.R., Kracher, G.P., Gottsch, J.D. and Stark, W.J. Therapeutic contact lenses. Ophthalmology, 97, 291-295 (1990). ~gAllansmith, M.R. Early stages of giant papillary conjunctivitis. Contact Lens ]., 17, 112-114 (1989). 3oIwasaki, W. Kosaka, Y., Momose, T. and Yasuda, T. Absorption of topical disodium cromogiycate and its preservatives by soft contact lenses. CLAO]., 14, 155-158 (1988).
11
© 1997 British Contact Lens Association
Printed in Great Britain
THERAPEUTIC CONTACT LENSES AND EYEDROPS A PROBLEM?
IS THERE
Martin P. Rubinstein* and Jane E. Evanst (Received 8th July 1996; in revised form 25th October 1996)
Abstract-- Numerous authors have investigated the interactions of contact lenses with their care solutions. Many reported hypersensitivity and toxicity reactions induced by the preservative in the care solution, especially with soft contact lenses. In medical contact lens practice the concurrent use of eyedrops in a patient wearing therapeutic contact lenses is a contentious issue. The usual practice is to prescribe unpreserved drops. In reviewing the literature, we found no evidence of complications using preserved eyedrops with such contact lenses in situ. The reluctance to prescribe preserved topical medication could stem from the evidence relating to contact lens care solutions. KEY WORDS:
Preservatives, benzalkonium chloride, chlorhexidine gIuconate, thiomersal, contact lenses, toxicity, eyedrops
Introduction
p
reservatives used in topical ophthalmic preparations can result in a wide variety of toxicity or hypersensitivity reactions. ~,2 The use of eyedrops in patients wearing therapeutic contact lenses is therefore a contentious issue. In one of the major contemporary contact lens texts advice is both confusing and contradictory. 3,4 The British National Formulary and the Monthly Index of Medical Specialities advise discontinuation of contact lens wear (particularly soft lenses) when using preserved preparations. Unpreserved drops are suggested as a safer alternative? There appears to be less concern regarding wearers of rigid gas-permeable lenses. This issue is of particular importance in medical contact lens practice where therapeutic lenses are widely used for specific purposes and often for periods exceeding 24h. In these circumstances, unpreserved drops are frequently prescribed, at considerably greater cost than their preserved equivalent. This perceived problem of using preserved eyedrops with contact lenses may stem from previous studies of contact lens interactions with care solutions. Contact Lens Interactions with Care S o l u t i o n s There is extensive literature describing the adverse ocular effects of preservatives in contact lens care solutions. The active ingredients and preservatives in contact lens care solutions may bind to and impregnate the constituent polymer and be retained for long periods of time. Soft Lenses
Gasset 6 reported a toxicity reaction in a unilateral aphakic soft lens wearer. On changing from an unpreserved to a preserved care regimen, after 3 days the eye became inflamed. This was attributed to the cytoxic effects of benzalkonium chloride (BAK) in the care * FCOptom PhD. t MCOptom, MPhil.
system used. BAK, a cationic preservative, has been shown to be a strong strong soft lens binder, indicating the influence of electrostatic forces. 3 Other authors have confirmed this effectJ ,8 High water content lenses absorb greater quantifies of BAK than do low water content lenses) Chlorhexidine gluconate (CLX), is also a weak cationic preservative. CLX in cleaning solutions has also been shown to accumulate in soft lenses. 1° It has a large molecular structure, hence its binding capacity is about one tenth of that of BAI~ However, CLX is very effectively bound to protein deposits on lens surfaces, which exacerbates the binding effect. At the concentration likely to be found in the tear film, following desorpfion from soft lenses, it produces little effect on the corneal epithelium. 11 Thiomersal is an anionic preservative and binding effects with soft lenses have been considered to be much weaker. However, thiomersal keratopathy has been another well documented problem 1~,1~ although cases are infrequently seen nowadays. In the current generation of multi-function, soft lens care solutions large molecular weight preservatives are used (e.g., Polyquad, Dymed). These resist diffusion into the lens matrix hence minimising potential problems. 14,15 But a recent study advocates caution in the use of such solutions. 16 Rigid Lenses
Various authors consider that binding and toxicity effects with PMMA and RGP materials are negligible. This has been reported for BAK, 17,18thiomersaP 9 and chlorhexidine, e° Other authors are more cautious regarding BAK-containing solutions and RGP lenses31,22 Cases have been reported of kerafifis thought to have been related to BAK binding. 23 Effects of Preservatives o n the Anterior Segment
Manifestations of BAK toxicity include marked conjuncrival hyperaemia and minimal chemosis. In an animal study using rabbits, corneal signs of BAK binding were
THERAPEUTICCONTACTLENSESAND EYEDROPS- - IS THEREA PROBLEM?
reported as superficial puntate epitheliopathy and filamentary keratitis. 24There has been a report of destructive change to corneal stromal cells by BAK in the presence of epithelial breaks. 2~With thiomersal, similar conjunctival signs have been reported along with mild superior limbitis and cystic changes in this area progressing with increased severity of reaction to diffuse epithelial keratitisY ,13In the longer term a vascularised pannus may develop in this areaY ,13.
Contact Lenses and Eyedrops Ophthalmologists and other hospital-based clinicians generally consider it unsafe to use preserved topical medication with therapeutic soft contact lenses in situ. Extended wear of soft lenses would theoretically pose a greater risk for toxicity reactions. However, several studies of bandage lens use with topical medication find no evidence of corneal damage. In the management of severe keratoconjunctivitis sicca and filamentary keratifis with 38% water content lenses, frequent administration of artificial tears preserved with 0.01% BAK caused no adverse effects over periods of wear of up to 8 weeks. 26 Other authors found similar resultsY In the treatment of bullous keratopathy with low and high water content lenses, various types of topical medication were used including steroids, lubricants, antibiotics and those for glaucoma. The lens replacement interval varied between 1.2 to 8.3 months. Another study reported the fitting of bandage lenses (high and medium water content and silicone) for short-term use. A wide variety of ocular conditions was treated with a large range of drops. No evidence of drug-related complications was found. % Similar conclusions have been drawn in users of daily wear soft lenses. In a study of the management of giant papillary conjunctivitis it was concluded that there were no problems associated with the use of disodium cromoglycate in soft lens wearers. 29 This was further substantiated in a study showing no accumulation of either the drug (sodium cromoglycate) or its preservative (BAK) in the lenses. 3° In addition it was concluded that the preserved drop could be safely applied directly onto a worn contact lens. Although the concentration of preservative (BAK) in eyedrops is generally higher than that in contact lens care solutions, the actual contact time with the contact lens is far less. A contact lens may soak in a care solution for many hours or even days whereas a topical drop will be fairly rapidly dissipated by the action of the tears and lids. Reflex lacrimation on instillation of a drop will further enhance this effect, particularly with the more irritating drugs. Retention of preservative/drug in a hydrogel lens is theoretically proportional to water content and thickness. The general tendency is for thinner lenses, reducing any potential problems. This relationship is particularly pertinent to the use of bandage therapeutic lenses which are generally of plano power and hence very thin, even in high water content materials. The 10
potential theoretical risk of any problems will also depend on frequency of drug instillation and duration of the treatment. For example, antibiotics are frequently prescribed by ophthalmologists as an adjunct to shortterm therapeutic contact lens use. The difference in cost between equivalent volumes of preserved and unpreserved drops is highly significant - - for example in the UK a 10ml bottle of chloramphenicol currently costs 50p compared with £4.92 for 20 unit dose Minims.
Conclusion The impression from our review of the literature is that the clinical manifestations of eyedrop preservative binding with contact lenses appears to be based on anecdotal evidence, perhaps relating to contact lens care solutions. We fully accept that preservatives and indeed some active ingredients in topical ophthalmic preparations can have side effects on the anterior segment of the eye. However, in the hospital-based contact lens clinic, where therapeutic lenses are often used on a short-term basis, we question the necessity to prescribe unpreserved drops. For longer-term use of such lenses we would still advocate caution. Address for Correspondence Optometry Unit, Department of Ophthalmology, University Hospital, Nottingham NG7 2UH. REFERENCES 1Kanstd, J.J. Clinical Ophthalmology, 2nd edn, Butterworths, London, Chapter 5, 100-149 (1989). 2 O'Connor Davis, P.H., Hopkins, G.A. and Pearson, R.M. The Actions and Uses of Ophthalmic Drugs, 3rd edn, Butterworths, London, Chapter 4, 67-79 (1989). Stewart-Jones, J.H., Hopkins, G.A. and Phillips, A.J. Drugs and solutions in contact lens practice and related microbiology. In: Phillips, A.J. and Stone, J. (eds), Contact Lenses, 3rd edn, Butterworths, London, 146-148 (1989). 4 Westerhout, D. Contact lenses in abnormal conditions. In: Phillips, A.J. and Stone, J. (eds), Contact Lenses, 3rd edn, Butterworths, London, 813-814 (1989). 5 British National Formulary. British Medical Association and the Royal Pharmaceutical Society of Great Britain, 32, 430-442 (1996). 6 Gasset, A.R. BAK toxicity to the human cornea. Am. J. Ophthal., 84, 169-171 (1977). 7 Vaughan, J.S. and Porter, D.A. A new in vitro method for assessing the potential toxicity of soft contact lens care solutions. CLAO J., 19, 54-57 (1993). s Hirji, N.K., Scott, J. and Sabell, A.G. Conjuncfival Sytology in hard and soft contact lens wear. Ophthal. Physiol. Opt., 5, 333-335 (1985). 9 Chapman, J.M., Cheeks, L. and Green, K. Interactions of benzalkonium chloride with soft and hard contact lenses. Arch. Ophthal., 108, 244-246 (1990). 10Lumbroso, P., Nhamias, M., Nhamias, S. and Tranche, P. A preliminary study of the adsorption and release of preservatives by contact lenses and collagen shields. CLAOJ., 22, 61-63 (1996). n Green, IC, Livingstone, V., Bowman, K. and Hull, D. Chlorhexidine effects on corneal epithelium and endothelium. Arch. Ophthal., 98, 1273-1278 (1990). 12Wright, P. and Mackie, I. Preservative related problems in soft contact lens wearers. Trans. Ophthal. Soc. UK, 102, 3-6 (1982). 1'~Wilson-Holt, N. and Dart, J.K.D. Thiomersal keratoconjunctivitis, frequency, clinical spectrum and diagnosis. Eye, 3, 581-587 (1989). 14Lowe, R. A review of the new multi-function lens care solutions. Optician, 2 0 7 (5454), 22-25 (1994). lS Bevington, R. Evaluation of benzalkonium chloride in a soaking/disinfecting rigid gas permeable regimen. Contact Lens Spectrum, 3 (3), 30-33 (1988). 16Atkins, N. and Allsopp, G. Multi-purpose solution intolerance.
MAR?FINP. RUBINSTEINAND JANEE. EVANS Diagnosis and management. Optician, 212 (5562), 22-30 (1996). 17Bergmanson, J.P. and Barbeito, R. Clinical assessment of ocular response to a multipurpose contact lens care solution. Ophthal. Physiol. Optics, 15, 535-544 (1995). is Hoffman, W. Ending the BAK-RGP controversy. Int. Contact Lens Clinic, 14, 31-33 (1987). 19Rebert, H. and Koffel, J.C. Evaluation of thlmerosal absorption. Contactologia, 11,172-175 (1989). ~0MacKeen, D.L. and Green, K. Chlorhexidine kinetics in hard contact lenses.J. Pharm. Pharmacol., 31,714-716 (1979). 21 Rosenthal, P., Chou, M.H. Salamone, J.C. and Israel, S.C. Preservative interaction with gas permeable lenses. Optician, 192 (5071), 33-38 (1986). 22 Herskowitz R. Solution interactions and gas permeable performance. Contact Lens]., 15, 3-5 (1987). 2a Sterling, J. and Hecht, A. BAK induced chemical keratitis? Contact Lens Spectrum, 3 (3), 62-64 (1988). 24 Imayasu, M., Moriyama, T., Ichijima, H., Ohashi, J., Petroll, W.M.
Jester, J.V. and Cavanagh, H.D. The effects of daily wear of rigid gas permeable contact lenses treated with contact lens care solutions containing preservatives on the rabbit cornea. CLAO ]., 20, 183-188 (1983). 2s Collin, B. Ultrastructural changes to corneal stromal cells due to ophthalmic preservatives. Acta Ophthahnol., 64, 72-74 (1986). 28Lemp, M.A. Bandage lenses and the use of topical solutions conraining preservatives. Ann. Ophthalrnol., 10, 1319-1321 (1978). 27Andrew, N.C. and Woodward, E.G. The bandage lens in bullous keratopathy. Ophthal. Physiol. Opt., 9, 66-68 (1989). 28Smiddy, W.E., Hamburg, T.R., Kracher, G.P., Gottsch, J.D. and Stark, W.J. Therapeutic contact lenses. Ophthalmology, 97, 291-295 (1990). ~gAllansmith, M.R. Early stages of giant papillary conjunctivitis. Contact Lens ]., 17, 112-114 (1989). 3oIwasaki, W. Kosaka, Y., Momose, T. and Yasuda, T. Absorption of topical disodium cromogiycate and its preservatives by soft contact lenses. CLAO]., 14, 155-158 (1988).
11