Putting vital stains in context

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<ul><li><p>SPECIAL ARTICLE</p><p>Putting vital stains in context</p><p>Clin Exp Optom 2013; 96: 400421 DOI:10.1111/j.1444-0938.2012.00802.x</p><p>Nathan Efron BScOptom PhD DScFAAOInstitute of Health and Biomedical Innovation,and School of Optometry and Vision Science,Queensland University of Technology, Kelvin Grove,Queensland, AustraliaE-mail: n.efron@qut.edu.au</p><p>While vital staining remains a cornerstone in the diagnosis of ocular disease and contactlens complications, there are many misconceptions regarding the properties of com-monly used dyes by eye-care practitioners and what is and what is not corneal stainingafter instillation of sodium fluorescein. Similarly, the proper use and diagnostic utility ofrose Bengal and lissamine green B, the other two ophthalmic dyes commonly used forassessing ocular complications, have similarly remained unclear. Due to the limitationsof vital stains for definitive diagnosis, concomitant signs and symptoms in addition to acomplete patient history are required. Over the past decade, there have been manyreports of a type of corneal stainingoften referred to as solution-induced cornealstaining (SICS)that is observed with the use of multipurpose solutions in combinationwith soft lenses, more specifically silicone hydrogel lenses. Some authors believe thatSICS is a sign of lens/solution incompatibility; however, new research shows that SICSmay be neither a measure of lens/solution biocompatibility nor true corneal staining,as that observed in pathological situations. A large component of SICS may be a benignphenomenon, known as preservative-associated transient hyperfluorescence (PATH).There is a lack of correlated signs and/or symptoms with SICS/PATH. Several proper-ties of SICS/PATH, such as appearance and duration, differentiate it from pathologicalcorneal staining. This paper reviews the properties of vital stains, their use and limita-tions in assessment of the ocular surface, the aetiology of corneal staining, characteris-tics of SICS/PATH that differentiate it from pathological corneal staining and what theSICS/PATH phenomenon means for contact lens-wearing patients.</p><p>Submitted: 9 June 2011Revised: 17 June 2012Accepted for publication: 19 June 2012</p><p>Key words: cornea, fluorescein, preservative-associated transient hyperfluorescence, solution-induced corneal staining, vital stains</p><p>The use of vital stains to detect ocularsurface abnormalities has been a mainstayfor eye-care professionals for nearly half acentury.1 Since their first use,24 much hasbeen learned regarding their physicalproperties and what the observed ocularsurface staining means with respect toocular health. With the advent of contact</p><p>lenses, ocular surface defects, disordersand diseases have increased in magni-tude.5,6 Differential diagnosis of ocularsurface disorders in contact lens wearers isoften difficult due to the overlappingsymptomatology and signs among differ-ent contact lens complications, as wellas non-contact lens-related disorders.711</p><p>The use of the three most commonlyused vital dyes, rose Bengal (RB),lissamine green B (LG), and sodiumfluorescein (NaFl),12 which havevarious properties and preferred uses(Table 1),1,3,1335 can impart a wealth ofinformation regarding the health of theocular surface and aid in differential</p><p>C L I N I C A L A N D E X P E R I M E N T A L</p><p>OPTOMETRY</p><p>Clinical and Experimental Optometry 96.4 July 2013 2012 The Author</p><p>400 Clinical and Experimental Optometry 2012 Optometrists Association Australia</p></li><li><p>diagnosis of ocular complications(Table 2).1,36,37 Due to ease of use andfamiliarity of eye-care professionals withvital dyes, there may have been an over-reliance on them for assessment of ocularhealth and a definitive cause of complica-</p><p>tions. Their value as a reliable diagnostictool is hampered due to several factors,especially our incomplete knowledge ofwhat these dyes do at a cellular andmolecular level. This has become appar-ent over the past decade due to the vast</p><p>research in dry eye syndromes (DES)38</p><p>and widespread use of silicone hydrogel(SiHy) lenses.39,40</p><p>The seminal study of Jones, McDougalland Sorbara39 in 2002 showed thathigh levels of asymptomatic corneal</p><p>Fluorescein Rose bengal Lissamine green B</p><p>At ocular pH (predominantly) Dianion (two negative charges);large population of monoanionswill also exist23</p><p>Dianion (two negative charges)24 Anion (single negative charge);large population of dianions willalso exist19</p><p>pKa a1 = 2.50; a2 = 3.81; a3 = 6.1023 a1 &lt; 0; a2 = 1.89; a3 = 3.9324 a1 = 1.31; a2 = 7.66; a3 = 11.7219</p><p>Spectra* Abs (nm): lmax = 474500[blue to cyan]23,28,30,75,80</p><p>Em (nm): lmax = 510550[green]28,29,75</p><p>Reflect/transmit = Orange75</p><p>Abs (nm): lmax = 543567,507522</p><p>[green to yellowish green]24,31,34,75</p><p>Em (nm): lmax = 565570[yellowish green to orange]3133,75</p><p>Reflect/transmit = Magenta75</p><p>Abs (nm): lmax = 624635[red]25,72,73,75</p><p>Reflect/transmit = Bluish green75</p><p>Illumination (Filter) Cobalt blue (Yellow Wratten #12)20 White light (None)1 White light (Red Wratten #24)84,161</p><p>Preferred use Cornea;13,26 conjunctiva (only withboth absorption and emissionfilters)27,144</p><p>Conjunctiva13,26; cornea (HSK, DE,other disorders with mucindeficiency)13,26,27</p><p>Conjunctiva;13,26 may be of valueassessing the cornea with a redfilter161</p><p>Test conductance NaFI-impregnated filter stripmoistened with a drop of sterilesaline (excess shaken off); assess1 to 4 minutes after applicationand several blinks27,84</p><p>RB-impregnated filter stripmoistened with a drop of sterilesaline (excess shaken off) or 25 mlof a 1% solution; assessed after afew minutes; perform towards endof ocular surface exam38,152</p><p>LG-impregnated filter stripmoistened with a drop of sterilesaline (excess shaken off) or 10 mlof 1% solution; assessed 1 to 4minutes after application84,161</p><p>Stains Healthy cells15,17,22,50,83</p><p>Damaged cells14,50</p><p>Dead cells17</p><p>Intracellular spaces14,17,21</p><p>Healthy cells18,21,35</p><p>Dead cells3,17</p><p>Damaged cells3,21</p><p>Mucous strands3</p><p>Damaged cells3,21</p><p>Dead cells3</p><p>Mucous strands3</p><p>Correlation with other stains Little correlation with RB andLG1,13,21</p><p>Little correlation with NaFI1,13,21</p><p>High correlation with LG3,13,16,84,95Little correlation with NaFI13</p><p>High correlation with RB3,13,16,84,95</p><p>pKa: the pH value at which equal concentrations of a molecule that differ by a single charge exist (X X X X- -+ pKa pKa pKa1 2 3 2 )lmax: peak/dominant wavelength(s), Abs: absorption, DE: dry eye, Em: emission, HSK: herpes keratitis, LG: lissamine green, NaFI: sodium fluorescein,RB: rose bengal.* Absorption, emission and reflection are highly sensitive to environment; emission and reflection spectra are also highly dependent upon lightsource/excitation wavelength.79 RB has a second lesser peak at 507522 nm; the two peaks are responsible for the magenta, which falls in the non-spectral purples (a combinationof blue and red).24,31</p><p>Table 1. Characteristics of the most commonly used vital stains for ocular surface visualisation</p><p>Putting vital stains in context Efron</p><p> 2012 The Author Clinical and Experimental Optometry 96.4 July 2013</p><p>Clinical and Experimental Optometry 2012 Optometrists Association Australia 401</p></li><li><p>Observation Staining Signs Symptoms</p><p>MechanicalForeign body(RGP&gt;SCL)1,11</p><p>NaFlzig-zag track1 Tearing121 Sudden stinging; pain/discomfort while trappedunder lens/eyelid;121</p><p>asymptomatic to milddiscomfort once foreignbody is removed123</p><p>Abrasion NaFlDeep or coalescedepithelial defect122</p><p>Tearing, blepharospasm, ciliaryinjection (severity of signsbased on extent of cornealinjury)121</p><p>Pain (often after lensremoval), FBS, reducedvisual acuity,photophobia122,123</p><p>Superior epithelialarcuate lesion (SEAL)1</p><p>(SiHy&gt;non-SiHySCL or RGP)11</p><p>NaFlsuperior arcuate;parallel to limbus7</p><p>None; some may experiencehyperaemia7</p><p>Most often asymptomaticduring lens wear/FBS afterlens removal; some mayexperience burning,irritation, lens awareness7</p><p>Lens binding/tight lenssyndrome1,11</p><p>(RGP/EW high waterhydrogel lenses)11</p><p>NaFlArc correspondingto lens edge or diffusestain in excessive bearing;1</p><p>RB/LGpossiblecircumlimbal103,124</p><p>Corneal oedema, conjunctivalhyperaemia, poor lensmovement, limbal indentation7,11</p><p>Irritation, visual defects,constant pain/discomfort,photophobia or may beasymptomatic123</p><p>ExposureKeratoconjunctivitissicca/dry eye syndrome(non-Sjgrens) (causedor exacerbated bycontact lens wear)122</p><p>NaFlpunctate epithelialkeratopathy ininterpalpebral region;7,104</p><p>RB/LGconjunctiva stainsmore intensely than cornea;cornea may also stain inmore severe cases37,127</p><p>Negligible tear meniscus at thelower lid, reduced tear break-uptime (TBUT)104</p><p>Dryness, burning/stinging,sandy or gritty FBS,itchiness, excess tearing(epiphora), contact lensintolerance104106</p><p>3/9 oclock staining(RGP)1,108</p><p>NaFlat the 3 and 9oclock positions;1,108</p><p>conjunctiva adjacent tocornea at 3/9 oclock (mostcommonly with highergrade corneal staining andsymptomatic patients)91</p><p>None to moderate bulbarhyperaemia adjacent to cornealstaining91,109</p><p>Asymptomatic (especiallywith low grade cornealstaining), discomfort, FBS,tearing, burning, reducedwearing times, andphotophobia91,126</p><p>Incomplete blink/lagophthalmos(inferior epithelialarcuate lesion/smilestain)1</p><p>(SCL)11</p><p>NaFlinferior arcuatepunctate band;1</p><p>RBlimited to inferonasalcornea and conjunctiva;37</p><p>LGconjunctiva possiblewhen symptomatic110</p><p>None; though low blink rate,increased contact lensdeposition, inferior limbalhyperaemia, lid wiperepitheliopathy may beobserved110,125</p><p>Asymptomatic or milddiscomfort, irritation,dryness, or contact lensintolerance110,125</p><p>Metabolic and toxicHypoxia [non-SiHySCL/PMMA RGP]11</p><p>NaFlcentral and diffuse111 Depending on severity: epithelial/stromal oedema and/or cell deathand desquamation, conjunctivalhyperaemia: chronic hypoxiacauses microcysts andneovascularisation111</p><p>Depending upon severity:temporary blurred vision,discomfort, photophobia orcan be asymptomatic111</p><p>Table 2. Pathological corneal staining: appearance, signs and symptoms. Lens type typically associated with complication in bracketsin first column. Images courtesy of Gary Foulks (keratitis sicca), Lyndon Jones (foreign body, lagophthalmos), the Association ofOptometric Contact Lens Educators (lens binding), the Digital Reference of Ophthalmology at the Edward S Harkness Eye Institute(bacterial keratitis) and the Bausch &amp; Lomb Image Library (abrasion, SEAL, hypoxia, chemical keratoconjunctivitis, CLPU, CLSD,HSV and protozoan keratitis). Reproduction of the 3/9 oclock image with permission from Morgan and colleagues.108</p><p>Putting vital stains in context Efron</p><p>Clinical and Experimental Optometry 96.4 July 2013 2012 The Author</p><p>402 Clinical and Experimental Optometry 2012 Optometrists Association Australia</p></li><li><p>Observation Staining Signs Symptoms</p><p>Chemicalkeratoconjunctivitis/conjunctivitismedicamentosa(SCL&gt;&gt;RGP)11</p><p>NaFlDiffuse punctatestaining of cornea and/orconjunctiva;112</p><p>RB/LGconjunctiva moreprominent than with NaFI112</p><p>Hyperaemia, eyelid oedema,corneal oedema, chemosis,pseudodendrites, follicles,scattered and/or disciform stromalinfiltrates, corneal epithelialerosions, SLK7,112</p><p>Irritation, ocular pain,stinging and burning (uponlens insertion in acutetoxicity), photophobia,blurred vision7,112</p><p>lnflammatoryContact lens-inducedperipheral ulcer(CLPU)</p><p>NaFloverlying smallepithelial defect stains113,114</p><p>Mild to moderate conjunctivalinjection near round, focalperipheral infiltrate 2 mm, focalexcavation, watery discharge;anterior chamber reaction, ifpresent, is very mild113,114</p><p>Moderate to severe pain/discomfort, photophobia,FBS (all milder than inmicrobial keratitis);asymptomatic in somecases113,114</p><p>Contact lens-inducedacute red eye(CLARE) (EW)113</p><p>NaFlwhen present isusually punctate,superficial, scattered113,114</p><p>Unilateral severe conjunctival andcircumlimbal hyperaemia, bothdiffuse and focal subepithelialinfiltrates most often in cornealperiphery, white and hazyoedematous cornea, anterioruveitis is common113,114</p><p>Acute onset of symptomsoften awakening patientsfrom sleep with irritation tomoderate/severe pain, FBS,burning, extremephotophobia113,114</p><p>Infiltrative keratitis(IK)(SCL)114</p><p>NaFloverlay infiltratesor SPK, if present7,103</p><p>Mild to moderate redness, cornealoedema, usually single, peripheral/mid-peripheral small, round, hazy,grey-white, cloudy, or amorphouscorneal infiltrates that may besubepithelial or anterior stromal,occasional watery discharge113,114</p><p>Mild to moderate symptoms(occasionallyasymptomatic) includingphotophobia, blurred vision,irritation113,114</p><p>Contact lens-inducedsuperior limbickeratoconjunctivitis(CL-SLK)(DW?)103</p><p>NaFlfine upper cornealpunctate staining, uppertarsal, bulbar, and limbalconjunctiva115</p><p>Mild to moderate superior tarsalpapillary hypertrophy (withmoderate reaction), superiorbulbar conjunctival hyperaemia,superior limbal hypertrophy,micropannus of superior cornealepithelium7,115</p><p>Mild to moderatediscomfort, dryness,burning, itching, blurredvision, contact lensintolerance7,114</p><p>Corneal limbalstem cell deficiency(CLSD)</p><p>NaFlatypical stainingof the conjunctivalisedepithelium on corneaadjacent to limbus116</p><p>Poor epithelialisation of thecorneal surface, recurrent erosion,chronic stromal inflammation,corneal neovascularisation,conjunctivalisation of the cornea116</p><p>Reduced vision,photophobia, tearing,blepharospasm, andrecurrent episodes of pain,contact lens intolerance116</p><p>InfectiousBacterial keratitis(SCL)11</p><p>NaFlulceration stainsintensely117</p><p>Epithelial ulcer, dense, suppurativestromal inflammation withindistinct edges, stromal oedemaand tissue loss, anterior chamberreaction (hypopyon possible),Desemets membrane folds,upper lid oedema, posteriorsynechiae, focal or diffuse cornealinflammation, conjunctivalhyperaemia, mucopurulentdischarge, endothelialinflammatory plaque7,117</p><p>Moderate to severe FBS,ocular pain, photophobia,tearing, decreased vision7,117</p><p>Table 2. Continued</p><p>Putting vital stains in context Efron</p><p> 2012 The Author Clinical and Experimental Optometry 96.4 July 2013</p><p>Clinical and Experimental Optometry 2012 Optometrists Association Australia 403</p></li><li><p>Observation Staining Signs Symptoms</p><p>Viralherpes simplexvirus keratitis (HSK)(Not associated withcontact lenses)</p><p>NaFlearly: mild finepunctate; late: branchingpatterns stain brightly;RB/LGearly: brightfine punctate; late: stainepithelial cells surroundingthe ulcer, terminalend-bulbs118</p><p>Unilateral, punctate keratitis,may progress to single ormultiple branching dendriticulcers, may present also asstromal keratitis, endothelitis,uveitis and retinitis118</p><p>Tearing, FBS, photophobia,ocular pain and blurring ofvision118</p><p>Viralepidemickeratoconjunctivitis(EKC)(Not typicallyassociated withcontact lenses)</p><p>NaFldiffuse fine,superficial keratitis duringfirst week and focal,elevated, punctate epitheliallesions develop by Day 6 to13118</p><p>Acute onset of unilateral,followed by bilateral papillaryand follicular reaction,bilateral preauricularlymphadenopathy, centralcorneal erosions during firstor second week after onset,coalescence of lesions toform coarse spots ofsubepithelial infiltrates,small-rounded subepithelialopacities may bepersistent118</p><p>FBS, photophobia,conjunctival hyp...</p></li></ul>