documentation of corneal epithelial defects with fluorescein-enhanced digital fundus camera...

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Clinical Technique

Documentation of corneal epithelial defects withfluorescein-enhanced digital fundus camera photographySimon J Dean FRANZCO,1,2 Elena S Novitskaya PhD,1,3 Tara CB Moore PhD,3 Johnny E Moore FRCOphth3

and Anant Sharma FRCOphth1

1Bedford Hospital NHS Trust, Bedford, 2Birmingham and Midland Eye Centre, Birmingham, and 3University of Ulster, Northern Ireland, UK

ABSTRACT

The advent of digital photography in the ophthalmic settinghas provided not only a means of documenting pathology, butwith instantaneous results, it is possible to aid clinical diagnosisand management.This study was designed to demonstrate theability to image corneal epithelial lesions stained with fluores-cein, with a digital fundus camera set on fluorescein angiogra-phy settings.The contrast of this technique demonstrated bothgross and subtle corneal epithelial lesions better than tradi-tional methods. The results obtained demonstrated the highsensitivity and high contrast images this technique can facilitatein every ophthalmic practice equipped with a fundus camerawith digital fluorescein angiography capability.

Key words: cornea, epithelial defect, filter, fluorescein,photography.

INTRODUCTION

The superficial layer of the cornea is frequently involved inocular surface disorders, where damage to epithelial cellsresult in corneal lesions visible at the slit-lamp.1 Recentmethodologies such as photomicrography and in vivo scan-ning confocal microscopy are being introduced to visualizeand evaluate previously undocumented corneal disorders.2,3

For reasons of cost and utility, traditional methods of docu-mentation of anterior segment ocular pathology with a slit-lamp camera, or even fundus camera, still remain popular inpractical ophthalmology.4,5 More recently, traditional film-based cameras have been supplanted by evolving digitaltechnology, which exhibit multiple benefits for medicalphotography. Digital photography provides instant high-quality images, without the necessity of waiting for film to beprocessed. These images can be stored in electronic healthrecords and are easily viewed and transferred.6 However, theobservation and photography of a transparent structure, such

as the cornea, still poses a significant challenge withinophthalmology. The clinical evaluation of corneal epithelialdisorders is greatly facilitated through the use of fluorescein,a hydrophilic vital dye that is able to demonstrate areas ofepithelial loss, and the extent of epithelial involvement ininflammatory disorders of the cornea, as well as monitoringepithelial healing.7,8

In order to increase the contrast resolution of fluores-cence, it is necessary to block the unwanted blue reflectedlight with a barrier filter. Therefore, two filters are needed tobest view fluorescence: a blue exciter filter (at around 470–490 nm) to stimulate fluorescence, and narrow bandpassgreen filter (centred around 530 nm) to visualize the fluores-cence only, while blocking the blue light.9 These principlesare the basis of fluorescein angiography, but can also beapplied to the subtle staining of corneal lesions. With theadvent of digital technology, the results are instantaneousand can potentially aid diagnosis and follow up of cornealepithelial lesions.10

METHODS

Ethical approval

Ethical approval for polymerase chain reaction testing wasprovided by The Office for Research Ethics Committees inNorthern Ireland.

Subjects

Four patients were included in the study: two with recur-rent herpes simplex virus (HSV) keratitis, one with partiallydecompensated Fuch’s endothelial dystrophy and one withdry eye. All patients underwent complete ophthalmologicexamination and were classified according to the appear-ance of epithelial involvement. The nature of the study andprocedures involved were fully explained to all participants,and informed consent to perform fluorescein-enhanced

� Correspondence: Mr Simon Dean, Bedford Eye Clinic, Bedford Hospital NHS Trust, Bedford MK42 9DJ, UK. Email: [email protected]

Received 28 August 2007; accepted 16 January 2008.

Clinical and Experimental Ophthalmology 2008; 36: 113–118doi: 10.1111/j.1442-9071.2008.01703.x

© 2008 The AuthorsJournal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists

mailto:[email protected]

photography was obtained before recruitment. At no timecould the patient be identified from the image alone. Theuse of volunteers followed the tenets of the Declaration ofHelsinki.

Fluorescein application and methodof visualization

For all patients, photographs were taken before and afterfluorescein application. A single drop of 2% sterile unpre-served fluorescein sodium solution (Minims FluoresceinSodium, Chauvin, Romford, UK) was applied to the inferiorconjunctival fornix. A time period of 1 min was allowedbefore photography. Photographs were taken with thedigital fundus camera (FF 450Plus IR, Carl Zeiss Meditec,Jena, Germany) with white light, blue (488 nm exciter filter),and on fluorescein settings (exciter and barrier filters). Forfamiliarity, slit-lamp photographs were also obtained tocompare with the fundus camera images. Digital images wereprocessed using Visupac software (Carl Zeiss Meditec, Inc,Oberkochen, Germany).

RESULTS

Examination with slit-lamp

Case 1: a typical HSV dendritic lesion (confirmed with poly-merase chain reaction) and an old corneal scar withingrowth of new vessels, mostly confined to the infer-otemporal quadrant of the right cornea.

Case 2: an atypical HSV lesion, with scarring and ulcerationof the right cornea.

Case 3: Fuch’s endothelial dystrophy. The cornea had visibleguttatae involving the entire endothelium, but only theinferotemporal cornea had started to decompensate, withmicrocystic oedema and bullae.

Case 4: a patient with mild dry eye, notable for no visiblecorneal pathology before staining. Slit-lamp examinationrevealed diffuse subtle superficial punctate keratitis fol-lowing fluorescein application.

Slit-lamp and fundus camera photography

In Case 1 (dendritic ulcer), pictures obtained with the funduscamera using white light revealed an old corneal scar, new

Figure 1. Herpes simplex virusdendritic ulcer following applicationof fluorescein: (a) white light photo-graph; (b) blue (488 nm) exciterfilter; and (c) exciter and barrierfilters in place (note absence ofcorneal light reflex).

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vessel ingrowth and characteristic staining of a dendriticlesion in the inferotemporal quadrant (Fig. 1a). An imagetaken with the blue/green 488 nm exciter filter also showedgreen fluorescence of the dendritic lesion (Fig. 1b).However, the fluorescence pattern was not as clear as theimages taken with the fundus camera on fluorescein angiog-raphy settings (Fig. 1c – exciter and barrier filters). In spite ofdiffusion of fluorescein into the corneal tissue, a clear pictureof the entire dendrite lesion was possible. The extremelyhigh contrast allowed visualization of the branching struc-ture of the ulcer, against the dark background of the cornea.

In addition, ulcer staining and staining from diffusion of thedye in the cornea were well defined from each other on thefluorescein-enhanced setting pictures, and could be opti-mized at the time of photography using the flash intensitysetting. Note also the lack of a corneal light reflex inFigure 1c, as it is blocked by the barrier filter, abolishingartifactual reflections.

In Case 2 (atypical HSV corneal scar), photographs takenwith white light demonstrated scarring and ulceration in theinferior cornea (Fig. 2a). Fluorescein staining of the epitheliallesions in a punctate distribution was observed in the pho-

Figure 2. Herpes simplex viruscorneal scar: (a) prior to fluoresceinapplication, all others followingfluorescein; (b) slit-lamp image withcobalt blue filter; (c) white light withfundus camera; (d) exciter filter; and(e) exciter and barrier filters (fluores-cein angiography settings).

Fluorescein-enhanced corneal photography 115


tograph obtained with the slit-lamp camera using cobalt bluelight (Fig. 2b). Images from the fundus camera followingfluorescein application (Fig. 2c,d) with white and blue light,respectively, illustrated the staining pattern over the scar.However, images of fluorescein staining with the fluoresceinangiography setting of the fundus camera (Fig. 2e) demon-strated considerably higher contrast. Detailed representationof each focus of staining was easily seen.

In Case 3 (Fuch’s endothelial dystrophy), the area of dec-ompensated cornea and overlying microcystic epithelialoedema was visible on photography with white light(Fig. 3a). Slit-lamp photography with the cobalt blue filterdemonstrated an improved delineation of decompensatedcornea (Fig. 3b). A similar image with the exciter filter on thefundus camera (Fig. 3c) showed a comparable stainingprofile. The fluorescein angiography setting (Fig. 3d) pro-vided improved contrast, without the corneal light reflex toconfuse the image, clearly highlighting the area of microcys-tic oedema, and area of epithelial bullae.

In Case 4 (mild dry eye), images demonstrated theappearance before instillation of fluorescein (Fig. 4a), withthe blue exciter filter following application of dye (Fig. 4b),and with fluorescein angiography settings (Fig. 4c). The mildsuperficial punctate keratitis visible at the slit-lamp was notof sufficient intensity to be photographed, and indeed theexciter filter alone on the fundus camera did not provide anadequate image.

Figure 4c demonstrated not only the superior contrast,but also the high sensitivity of this technique, with its abilityto document even subtle staining.

DISCUSSION

Vital staining with fluorescein is a standard practice in oph-thalmology to distinguish and document corneal epithelialdiseases. Visualization techniques of staining patterns atmacro- and microscopic levels have been described previ-ously in numerous studies.3,11 Many researchers also utilizeanterior segment fluorescein angiography to assess vascularchanges in diseases of the cornea, iris and limbal regions. Ithas been concluded that anterior segment fluoresceinangiography gives valuable information regarding the vascu-lar architecture, flow and leakage in inflammatory diseases ofthe cornea.12,13 Now that digital photography is standard inmost practices, instant imaging is possible with the addedadvantage of the technique we describe previously, to furtherenhance documentation and possibly aid diagnosis in cornealdisorders.

The results of this study demonstrated the advantages ofthe instant high-contrast imaging possible using digitalfundus camera fluorescein angiography settings, for captureof fluorescein staining of epithelial corneal lesions. Withthis technique, distracting corneal light reflexes, inherent inall forms of corneal photography, are abolished by theaction of the barrier filter. This provides accurate andartifact-free documentation of the anterior corneal surface.As well as demonstrating very detailed epithelial defectstaining, it was also possible to visualize diffusion of dyeinto the surrounding stroma. This penetration of fluoresceinmay be due to loss of barrier function secondary to epithe-lial sloughing and disruption of intercellular tight junctions.

Figure 3. Fuch’s endothelial dys-trophy with partial corneal decom-pensation, following fluoresceinapplication: (a) fundus camera,white light; (b) slit-lamp camera,cobalt blue filter; (c) fundus camera,exciter filter; and (d) fundus camera,exciter and barrier filters.

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It therefore may also be possible to use this method todetermine the degree of loss of epithelial barrier function,similar to fluorophotometry, but for the cornea rather thanthe anterior chamber.

We found the high sensitivity of this method required awashout period for fluorescein dilution before images couldbe obtained without loss of contrast due to masking fluores-cence of the tear film. We have now reduced the concentra-tion of fluorescein applied to 0.25% rather than 2%, whichstill maintains adequate staining of even subtle lesions.Minute amounts of staining can be documented, making ituseful for following corneal pathologies, such as superficialpunctate keratitis, as well as gross epithelial defects. In addi-tion, the use of digital photography allows automatic docu-mentation of the time and date for reliable archival andcomparison over time.

The ease of use of this technique and widespread avail-ability of the digital camera systems may contribute to the

efficacy of patients’ follow up during assessment of cornealepithelial lesions.

ACKNOWLEDGEMENT

This research was in part funded by a HPSS Research &Development Office, Recognized Research Grant (9.38),Northern Ireland (CBT Moore).

REFERENCES

1. Soong H. Corneal epithelium. In: Yanoff M, Duker J, eds.Ophthalmology. Barcelona: Mosby, 1999; 5.2.1–5.2.8.

2. Patel DV, McGhee CN. Contemporary in vivo confocalmicroscopy of the living human cornea using white light andlaser scanning techniques: a major review. Clin Experiment Oph-thalmol 2007; 35: 71–88.

Figure 4. Mild dry eye with super-ficial punctate staining visible fol-lowing application of fluorescein: (a)white light; (b) exciter filter; and (c)exciter and barrier filters.

Fluorescein-enhanced corneal photography 117


3. Tabery HM. Healing of recurrent herpes simplex corneal epi-thelial lesions treated with topical acyclovir A non-contactphotomicrographic in vivo study in the human cornea. ActaOphthalmol Scand 2001; 79: 256–61.

4. Aandekerk AL, Steenbergen EJ. Equipment for ophthalmol-ogical photography: Part II. J Audiov Media Med 1990; 13: 4–8.

5. Wassill KH, Dick B. A simple and rapid method for photo-graphic documentation of findings using the slit lamp. Ophthal-mologe 1994; 91: 399–402.

6. Saine P, Tyler M. Ophthalmic Photography: Retinal Photography,Angiography, and Electronic Imaging. Boston, MA: Butterworth-Heinemann, 2002.

7. Singh JK, Dhawahir FE, Hamid AF, Chell PB. The use of dye inophthalmology. J Audiov Media Med 2004; 27: 62–7.

8. Kim J. The use of vital dyes in corneal disease. Curr OpinOphthalmol 2000; 11: 241–7.

9. Gutner R, Miller D. Inside the fundus camera. Ann Ophthalmol1983; 15: 13–16.

10. Novitskaya ES, Dean S, Moore J, Sharma A. A novel method tostudy fluorescein staining of the ocular surface using the fluo-rescein angiogram setting of the fundus camera. Cont Lens Ante-rior Eye 2007; 30: 258–9.

11. Mocan MC, Irkec M. Fluorescein enhanced confocal micros-copy in vivo for the evaluation of corneal epithelium. ClinExperiment Ophthalmol 2007; 35: 38–43.

12. Saari KM. Anterior segment fluorescein angiography in inflam-matory diseases of the cornea. Acta Ophthalmol (Copenh) 1979;57: 781–93.

13. Fariza E, Ormerod LD, O’Day T, Celorio JM. Practical anteriorsegment fluorescein angiography. Graefes Arch Clin Exp Ophthal-mol 1991; 229: 105–10.

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