re: putting vital stains in context

1
Letters to the editor Clin Exp Optom 2013; 96: 508–512 Re: Putting vital stains in context Eric Papas* †§ PhD BScOptom DipCLP FAAO Lyndon Jones || BSc PhD FCOptom DipCLP DipOrth FAAO * Brien Holden Vision Institute, Sydney, Australia School of Optometry and Visual Science, University of New South Wales, Sydney, Australia § Vision CRC, Sydney, Australia || School of Optometry & Vision Science, University of Waterloo, Waterloo, Ontario, Canada E-mail: [email protected] DOI:10.1111/cxo.12058 EDITOR: We note the recent article by Efron, 1 in which considerable space is given to solution-induced corneal staining (SICS) and preservative-associated transient hyper- fluorescence (PATH). In his concluding comments, Professor Efron makes the asser- tion ‘I feel that this phenomenon (that is, SICS) can be largely explained by PATH’. While commending this otherwise excellent review, we feel that this particular conclu- sion is premature, as it discounts two pieces of relevant information, both of which will be familiar to those who work with fluores- cein under these circumstances. First, it is a commonly remarked-upon fact, as well as the subject of a recent report, 2 that the epithelial appearance corresponding to SICS can be observed without the instillation of fluorescein. The PATH hypothesis is that preservatives released from soft contact lenses interact with fluorescein and the ocular surface giving the appearance of staining. 3 It seems evident that removing fluorescein molecules from the system should eliminate all signs of PATH. Second, the PATH hypothesis has not been able to explain the punctate nature of the staining pattern observed in SICS. Given that preservative molecules in multipurpose solutions are at least 10,000 times smaller than corneal epithelial cells, the mechanism implied by PATH would be expected to produce a uniform distribution of the pre- servative and associated fluorescein mol- ecules across the cornea. Consequently, the fluorescent appearance should also be uniform, rather than the discrete punctate spots, often in an annular pattern, that actu- ally occur. To date, PATH has been founded on theory and an in vitro model that uses liposomes rather than corneal epithelial cells. We suggest that acceptance of the PATH theory requires that it must also be consistent with readily observable phenom- ena, such as those described above. Unless and until that is the case, while remaining an interesting hypothesis to explain the obser- vation seen when certain contact lens solu- tions and materials are used synergistically, it cannot be seen as proven. REFERENCES 1. Efron N. Putting vital stains in context. Clin Exp Optom 2013; 96: 400–421. 2. Maldonado-Codina C, Read ML, Dobson C, Morgan PB. Case Rreport: Can SICS be observed with rose bengal and lissamine green? Am Acad Optom (Poster Presentation). 2012: 125372. 3. Bright FV, Merchea MM, Kraut ND, Maziarz EP, Liu XM, Awasthi AK. A preservative-and-fluorescein interaction model for benign multipurpose solution-associated transient corneal hyperfluore- scence. Cornea 2012; 31: 1480–1488. Response to Re: Putting vital stains in context Nathan Efron* PhD DSc * School of Optometry and Vision Science and Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia E-mail: [email protected] DOI:10.1111/cxo.12062 EDITOR: There has been considerable dis- cussion in recent times about the origins of solution-induced corneal staining (SICS) and I welcome this opportunity to further clarify some points raised in my paper 1 in relation to certain issues highlighted by Drs Papas and Jones. 2 Part of the difficulty in understanding these phenomena relates to the imprecise terminology used. For example, Drs Papas and Jones state ‘. . . SICS can be observed without the instillation of fluorescein.’ This statement is self- contradictory because it is impossible to observe staining (SICS) in the absence of a stain (fluorescein). Presumably, Drs Papas and Jones are referring to a different and possibly associated phenomenon of altered reflectance of the superficial epithelium, observed in white light, following instillation into the eye of certain contact lens multipur- pose solutions (MPS). This phenomenon, which needs to be called something differ- ent (vide infra), has recently been observed by Maldonado-Codina and colleagues. 3 Preservative-associated transient hyper- fluorescence (PATH) is essentially a model that helps explain the time course of SICS when MPS are placed into the eye in the presence of fluorescein. 4 As Drs Papas and Jones correctly describe, hyper-reflectance can be observed prior to fluorescein installa- tion. The physical origins of the observed signals (reflectance scattering viewed in white light and fluorescein emission seen following instillation of fluorescein) are very different and one is well served not to confuse the two and/or interpret them out of context. They might well have the same origin (vide infra) but the signals are differ- ent and there is no proof they are or should be related. The size of these hyper-reflecting areas (21.6 ± 3.9 μm) 3 is broadly consistent with the known diameter of superficial human corneal epithelial cells, which range in size from 20 to 37 μm. 5 It is well-known that cells that are going through natural apoptosis are different from other cells. For example, as part of the natural pro- gression toward apoptosis, the cell surface becomes enriched in phosphatidylserine, 6 which is anionic under physiological con- ditions. Most common preservative agents used in MPS are polycations under physi- ological conditions. 7 Anions and cations can be expected to interact; therefore, MPS may simply be highlighting sub-sets of corneal epithelial cells that are apoptotic. An individual molecule of a preservative agent is substantially smaller in comparison to either the wavelength of visible light or a CLINICAL AND EXPERIMENTAL OPTOMETRY Clinical and Experimental Optometry 96.5 September 2013 © 2013 The Authors 508 Clinical and Experimental Optometry © 2013 Optometrists Association Australia

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Page 1: Re: Putting vital stains in context

Letters to the editorClin Exp Optom 2013; 96: 508–512

Re: Putting vital stainsin context

Eric Papas*†§ PhD BScOptom DipCLPFAAOLyndon Jones|| BSc PhD FCOptom DipCLPDipOrth FAAO* Brien Holden Vision Institute, Sydney, Australia† School of Optometry and Visual Science, Universityof New South Wales, Sydney, Australia§ Vision CRC, Sydney, Australia|| School of Optometry & Vision Science, University ofWaterloo, Waterloo, Ontario, CanadaE-mail: [email protected]:10.1111/cxo.12058

EDITOR: We note the recent article byEfron,1 in which considerable space is givento solution-induced corneal staining (SICS)and preservative-associated transient hyper-fluorescence (PATH). In his concludingcomments, Professor Efron makes the asser-tion ‘I feel that this phenomenon (that is,SICS) can be largely explained by PATH’.While commending this otherwise excellentreview, we feel that this particular conclu-sion is premature, as it discounts two piecesof relevant information, both of which willbe familiar to those who work with fluores-cein under these circumstances.

First, it is a commonly remarked-uponfact, as well as the subject of a recentreport,2 that the epithelial appearancecorresponding to SICS can be observedwithout the instillation of fluorescein.The PATH hypothesis is that preservativesreleased from soft contact lenses interactwith fluorescein and the ocular surfacegiving the appearance of staining.3 It seemsevident that removing fluorescein moleculesfrom the system should eliminate all signs ofPATH.

Second, the PATH hypothesis has notbeen able to explain the punctate nature ofthe staining pattern observed in SICS. Giventhat preservative molecules in multipurposesolutions are at least 10,000 times smallerthan corneal epithelial cells, the mechanismimplied by PATH would be expected toproduce a uniform distribution of the pre-servative and associated fluorescein mol-

ecules across the cornea. Consequently,the fluorescent appearance should also beuniform, rather than the discrete punctatespots, often in an annular pattern, that actu-ally occur.

To date, PATH has been founded ontheory and an in vitro model that usesliposomes rather than corneal epithelialcells. We suggest that acceptance of thePATH theory requires that it must also beconsistent with readily observable phenom-ena, such as those described above. Unlessand until that is the case, while remaining aninteresting hypothesis to explain the obser-vation seen when certain contact lens solu-tions and materials are used synergistically, itcannot be seen as proven.

REFERENCES1. Efron N. Putting vital stains in context. Clin

Exp Optom 2013; 96: 400–421.2. Maldonado-Codina C, Read ML, Dobson C, Morgan

PB. Case Rreport: Can SICS be observed with rosebengal and lissamine green? Am Acad Optom (PosterPresentation). 2012: 125372.

3. Bright FV, Merchea MM, Kraut ND, Maziarz EP,Liu XM, Awasthi AK. A preservative-and-fluoresceininteraction model for benign multipurposesolution-associated transient corneal hyperfluore-scence. Cornea 2012; 31: 1480–1488.

Response to Re: Puttingvital stains in context

Nathan Efron*† PhD DSc* School of Optometry and Vision Science and† Institute of Health and Biomedical Innovation,Queensland University of Technology, Kelvin Grove,Queensland, AustraliaE-mail: [email protected]:10.1111/cxo.12062

EDITOR: There has been considerable dis-cussion in recent times about the origins ofsolution-induced corneal staining (SICS)and I welcome this opportunity to furtherclarify some points raised in my paper1 inrelation to certain issues highlighted by DrsPapas and Jones.2 Part of the difficulty inunderstanding these phenomena relatesto the imprecise terminology used. Forexample, Drs Papas and Jones state ‘. . . SICS

can be observed without the instillationof fluorescein.’ This statement is self-contradictory because it is impossible toobserve staining (SICS) in the absence of astain (fluorescein). Presumably, Drs Papasand Jones are referring to a different andpossibly associated phenomenon of alteredreflectance of the superficial epithelium,observed in white light, following instillationinto the eye of certain contact lens multipur-pose solutions (MPS). This phenomenon,which needs to be called something differ-ent (vide infra), has recently been observedby Maldonado-Codina and colleagues.3

Preservative-associated transient hyper-fluorescence (PATH) is essentially a modelthat helps explain the time course of SICSwhen MPS are placed into the eye in thepresence of fluorescein.4 As Drs Papas andJones correctly describe, hyper-reflectancecan be observed prior to fluorescein installa-tion. The physical origins of the observedsignals (reflectance scattering viewed inwhite light and fluorescein emission seenfollowing instillation of fluorescein) are verydifferent and one is well served not toconfuse the two and/or interpret them outof context. They might well have the sameorigin (vide infra) but the signals are differ-ent and there is no proof they are or shouldbe related.

The size of these hyper-reflecting areas(21.6 ± 3.9 μm)3 is broadly consistent withthe known diameter of superficial humancorneal epithelial cells, which range in sizefrom 20 to 37 μm.5 It is well-known that cellsthat are going through natural apoptosis aredifferent from other cells.

For example, as part of the natural pro-gression toward apoptosis, the cell surfacebecomes enriched in phosphatidylserine,6

which is anionic under physiological con-ditions. Most common preservative agentsused in MPS are polycations under physi-ological conditions.7 Anions and cations canbe expected to interact; therefore, MPS maysimply be highlighting sub-sets of cornealepithelial cells that are apoptotic.

An individual molecule of a preservativeagent is substantially smaller in comparisonto either the wavelength of visible light or a

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Clinical and Experimental Optometry 96.5 September 2013 © 2013 The Authors

508 Clinical and Experimental Optometry © 2013 Optometrists Association Australia