NEUROPHTHALMOLOGY

Sensitivity and specificity of monochromatic photographyof the ocular fundus in differentiating optic nerve headdrusen and optic disc oedemaOptic disc drusen and oedema

Pablo Gili & Patricia Flores-Rodríguez & Julio Yangüela &

Javier Orduña-Azcona & María Dolores Martín-Ríos

Received: 26 July 2012 /Revised: 26 October 2012 /Accepted: 20 November 2012 /Published online: 5 December 2012# Springer-Verlag Berlin Heidelberg 2012

AbstractBackground Evaluation of the efficacy of monochromaticphotography of the ocular fundus in differentiating opticnerve head drusen (ONHD) and optic disc oedema (ODE).Methods Sixty-six patients with ONHD, 31 patients withODE and 70 healthy subjects were studied. Colour and mono-chromatic fundus photography with different filters (green,red and autofluorescence) were performed. The results wereanalysed blindly by two observers. The sensitivity, specificityand interobserver agreement (k) of each test were assessed.Results Colour photography offers 65.5 % sensitivity and100 % specificity for the diagnosis of ONHD. Monochro-matic photography improves sensitivity and specificity and

provides similar results: green filter (71.20 % sensitivity,96.70 % specificity), red filter (80.30 % sensitivity, 96.80 %specificity), and autofluorescence technique (87.8 % sensitivi-ty, 100 % specificity). The interobserver agreement was goodwith all techniques used: autofluorescence (k00.957), greenfilter (k00.897), red filter (k00.818) and colour (k00.809).Conclusions Monochromatic fundus photography permitsONHD and ODE to be differentiated, with good sensitivityand very high specificity. The best results were obtainedwith autofluorescence and red filter study.

Keywords Optic disk drusen . Diagnosis .Ophthalmoscopy .

Fluorescein angiography . Echography . Fundus photography

Introduction

The differentiation between optic disc oedema (ODE) andpseudopapilloedema due to optic nerve head drusen (ONHD)is clinically significant. Superficial drusen can usually be easilyidentified in an ophthalmoscopy. However, it can be difficult todifferentiate between the two, especially in patients with burieddrusen. Different methods have been described for the diagno-sis of ONHD: fundus exploration [1], fluorescein angiographyand autofluorescence [2, 3], scanning laser ophthalmoscopy(SLO) [4], computerised axial tomography [5] and recently,optical coherence tomography [6]. Since its appearance in the1980’s, ocular ultrasound has been considered the gold stan-dard test for diagnosing ONHD [7].

The use of digital fundus cameras and telemedicine hasgrown considerably in clinical practice for pathological studyof the fundus [8]. This equipment permits colour photographs,

P. Gili : P. Flores-Rodríguez : J. Yangüela : J. Orduña-AzconaOphthalmology Unit, Alcorcon Foundation University Hospital,Madrid, Spain

P. GiliHealth Sciences Faculty, European University of Madrid,Madrid, Spain

P. Flores-RodríguezPontificia Universidad Católica de Valparaíso,Valparaíso, Chile

M. D. Martín-RíosPreventative Medicine Unit, Rey Juan Carlos Hospital,Madrid, Spain

P. Gili (*)Unidad deOftalmología, Hospital Universitario FundaciónAlcorcón,C/ Budapest 1, 28922 Alcorcón,Madrid, Spaine-mail: pgili@fhalcorcon.es

Graefes Arch Clin Exp Ophthalmol (2013) 251:923–928DOI 10.1007/s00417-012-2223-1

photographs with filters and photographs with various dyes tobe taken. [9]

The aim of this study was to assess the effectiveness ofocular fundus photography using monochrome filters (green,red and autofluorescence), in order to differentiate betweenpseudopapilloedema due to ONHD and papilloedema, assess-ing the sensitivity, specificity and interobserver agreement.

Material and methods

The study was approved by the ethics committee of theAlcorcon Foundation University Hospital (Spain), and wasconducted under the principles of the Helsinki Declaration.

We conducted a cross-sectional, descriptive study that in-cluded patients with ONHD, patients with ODE, and healthycontrol subjects during the period between 1st March, 2009and 1st May, 2011 at the ophthalmology unit of our hospital.

All patients included in the study received a completeophthalmologic examination, which initially included themea-surement of best corrected visual acuity (BCVA LogMARscale), ETDRS optotypes (4m), anterior segment examination,an ophthalmoscopic examination under pharmacologicalmydriasis (indirect fundoscopy), an ultrasound B scan

(OTI Ophthalmic Technologies Inc.; http://2774.ca.all.biz),photographs of the optic disc using a mydriatic fundus camerawith 20º (29x) (FF 450 plus IR www.meditec.zeiss.com), andobtaining colour and monochromatic photographs with differ-ent filters (green, red, and autofluorescence).

Inclusion criteria

Three groups of patients were included: patients withONHD (visible and buried), patients diagnosed with ODE,and control subjects.

1) Optic nerve head drusen (ONHD): Patients with sus-pected optic disc drusen were consecutively selected.Cases with visible and/or buried unilateral or bilateraloptic disc drusen were included, confirmed with ultra-sound B (gold standard).

2) Optic disc oedema (ODE): Patients with ODE of differ-ent aetiologies were consecutively included. A com-plete neurological and ophthalmological examinationwas performed with definitive diagnoses of ODE.

3) Healthy control subjects: These participants had an opti-mal corrected visual acuity > 20/40, small refractivedefects (< ± 2.00 D), transparent ocular media and normal

Fig. 1 Study of optic nerve head drusen (ONHD) visibility in colour photography, green filter, red filter and autofluorescence by twoobservers. p calculated – chi-square test

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appearance of the optic nerve, as indicated by colourphotography. Intraocular pressure (IOP) was evaluatedwith Perkins’ applanation tonometer (<21 mmHg)(http://www.clement-clarke.com/).

Exclusion criteria

The following were excluded from the study: patients forwhom certain diagnostic tests could not be performed, as aresult of media opacity that prevented fundus photography;patients from whom there was a lack of cooperation for any ofthe tests; and, in the ODE group, those who had not undergoneconfirmation tests.. Cases in which ONHD could not beconfirmed by ultrasound B scanning were also excluded.

Ocular fundus photography

Images of the ocular fundus were obtained with a mydriaticcamera with telecentric optics (Zeiss FF450 IR plus) andwith a digital archiving system (Visupac 451, version 4.4.4.

http://www.meditec.zeiss.com). Colour photographs weretaken using a camera in high resolution colour 3CCD:AVT ZK-5 (resolution 2588×1958).

For the study with monochromatic light, a black andwhite Kodak Megaplus high-resolution 1.6 (1280 × 1024)camera was used. The equipment used included the followingfilters:

– Green filter. (540 nm).– Red filter. (630 nm).– Angiography filters [blue exciter filter (490 nm) and

yellow-green barrier filter (525 nm)] for evaluation ofautofluorescence or pre-injection autofluorescence.

Imaging tests were analysed blindly by two observerswith different academic backgrounds: ophthalmologist(reviewer 1), optometrist (reviewer 2). The observershad to assess each image, shown in random order, forthe existence of visible drusen in colour photography,with green filter and with red filter. With autofluores-cence filters, they determined whether autofluorescencewas positive or negative.

Fig. 2 Fundus photographyin visible optic nerve headdrusen (ONHD): a Colour, bgreen filter, c red filter, dpositive phenomenon ofautofluorescence

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Statistical analysis

Sample size was estimated considering 80 % sensitivity and15 % accuracy, a 1/2 ratio for optic disc oedema and ONHD,and 1/1 for ONHD and controls, a confidence level of 95 %and a power of 80 %. The minimum estimated size for theseconsiderations was 28 eyes with optic disc oedema, 56 withONHD and 56 controls.

All patients with bilateral pathologies of ODE or ONHDand healthy subjects, with only one eye of each patientincluded in the study, were randomly selected. In the de-scriptive analysis, the qualitative variables are expressed asproportions, and the quantitative variables using their meansand standard deviations (SD). In the qualitative variables,

the sensitivity and specificity were analysed with 95 %confidence intervals of each of the imaging techniques;ultrasound B was considered as the gold standard test forthe diagnosis of ONHD.

Kappa values were utilised to determine interobserver reli-ability for categorical variables; values of 0.81–1.0 are indica-tive of excellent agreement; 0.61–0.80, substantial agreement;0.41–0.60, moderate agreement; 0.21–0.40, fair agreement; 0–0.20, slight agreement; and values ≤ 0, poor agreement [10].

In order to compare mean age among the three groups, weused the ANOVA test, and the Kruskal–Wallis test was usedfor the BCVAvariable (non-normal distributions). Bonferronicorrection was used to correct these multiple comparisons,and p≤0.01 indicated a statistically significant difference.

Fig. 3 Fundus photographyin buried optic nerve headdrusen (ONHD): a Colour, bgreen filter, c red filter, dpositive phenomenon ofautofluorescence

Table 1 Detection of opticnerve head drusen (ONHD) withcolour and monochromatic fun-dus photography (observer 1)

Colour presence n (%) Colour absence n (%) p

Green Filter: drusen presence 40 (93.0) 7 (30.4) < 0.0001

Red Filter: drusen presence 42 (97.7) 11 (47.8) < 0.0001

Autofluorescence: Positive 42 (97.7) 16 (69.6) 0.002

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Statistical analysis was performed with the SPSS pro-gram for Windows (version 15.0.1, http://www.01.ibm.com/software/analytics/spss/and MedCalc (version 7.3.0.1, http://www.medcalc.org/).

Results

The studied population included: 66 patients with ONHD (38visible and 28 buried), with a mean age (SD) of 43.4 (18.8)years (60 % women); 31 patients diagnosed with ODE (16papilloedemas, nine ischemic optic neuropathies, three neuritisor papillitis, two cases of retina central vein occlusion, and onepapillary oedema due to hypotonia), with mean age of 49.8(15.8) years (39 % women); and 70 control subjects with meanage of 41.5 (15.8) years (69 % women). Mean age was notsignificantly different among the three groups (p00.078). TheBCVA (LogMAR scale) was significantly different among thethree groups (p<0.0001); the control group showed betterBCVA values, with a mean (SD) of 0.02±0.04 logMAR; theONHD group showed a mean of 0.11±0.19 logMAR; and theEDO group had the worst BCVAvalues, with a mean of 0.32±0.35 logMAR.

The monochromatic fundus photography showed ahigher detection rate of ONHD than colour photography.Comparison of percentage of detection rates betweenobservers showed no statistically significant differences.(Figs. 1, 2 and 3).

Comparison of detection of ONHD between colour fundusphotography and monochromatic photography showed statis-tically significant differences for both observers. (Table 1)

The diagnostic accuracy rates in the differential diagnosisbetween ONHD and ODE with monochrome filters showedresults of higher sensitivity to colour photography, with similarspecificity. Autofluorescence technique obtained the highestvalues of sensitivity (87.8 %), with significant differences inrelation to colour fundus photography (p00.004). The greenand red filters show significant differences in sensitivity, al-though they are not statistically significant. There are no

significant differences in specificity between filters and colourfundus photography. (Table 2)

Interobserver agreement in terms of differentiating ONHDand ODE showed good–excellent results. The highest rates ofagreement were obtained with autofluorescence. (Table 3)

Discussion

Ophthalmoscopy was the main method of diagnosis of opticdisc drusen until the advent of other techniques such as auto-fluorescence, computed tomography (CT) scan and ultra-sound. Superficial drusen are easy to identify. However, theywere only present in 42 % [11] and 47 % [12] of the ONHDcases. Other ophthalmoscopic characteristics, such as papil-lary elevation, blurred edges, the absence of excavation andvascular alterations means suspicion of their presence [13].

Ultrasound B is considered the most reliable method fordetecting ONHD. It permits buried drusen to be detected,even in uncooperative children or in patients with mediaopacity [14]. ONHD presents high reflectivity with low gainlevels, due to its high calcium content [7]. Large drusen areeasily detectable; however, the experience and skill of thesonographer are important [15] in small drusen. Further-more, not all ophthalmologists have access to ultrasoundequipment or have sufficient experience using it.

The use of digital fundus cameras has spread widely amongophthalmologists and other health professionals. They are easyto operate and provide high quality images. For this reason, we

Table 2 Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with colour image, green filter, red filter andautofluorescence (observer 1)

Sensitivity (95 % CI) Specificity (95 % CI) PPV (%) (95%CI) NPV (%) (95%CI)

Colour 65.50 % 100 % 100 57.41

(52.9–77.4) (98.4–100) (98.8–100) (43.3–71.5)

Green filter 71.20 % 96.70 % 97.92 61.22

(59.5–82.9) (88.9–100) (92.8–100) (46.6–75.9)

Red filter 80.30 % 96.80 % 98.15 69.77

(69.9–90.7) (88.9–100) (93.7–100) (54.9–77.8)

Autofluorescence 87.80 % 100 % 100 79.49

(79.3–96.5) (98.4–100) (99.14–100) (65.6–93.4)

Table 3 Interobserver agreement (kappa) in diagnosis of optic nervehead drusen (ONHD)

Kappa IC 95 %

Colour 0.809 0.69–0.93

Green filter 0.897 0.81–0.98

Red filter 0.818 0.70–0.93

Autofluorescence 0.957 0.90–1.00

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proposed to evaluate the usefulness of colour and monochro-matic photography with different filters in the differential di-agnosis between pseudopapilloedema due to ONHD andODE.

Analysis of the diagnostic validity of colour photographyin order to differentiate between ONHD and ODE obtainedhigh specificity (100 % for both observers), but moderatesensitivity (65.50 % and 57.60 %), with good interobserveragreement (K00.809). Therefore, when superficial papillarydrusen are visualised, the diagnosis offers little doubt, butburied ONHD may go unnoticed.

The use of green filters (red-free light), was first describedas a diagnostic tool in ONHD in 1978 [16]. In this study,drusen with 71 % sensitivity (observer 1) and 64 % (observer2) were identified, higher than those found with colour reti-nography. Interobserver agreement was very good (K00.897).

No previous studies supporting the usefulness of red mono-chromatic light with fundus photography in the diagnosis ofONHD were found. It can be concluded that greater capacityof red light penetration (630 nm) could facilitate the identifi-cation of optic disc drusen, especially buried or buried forms.This was confirmed by the results: the red filter identified80 % (observer 1) and 67 % (observer 2) of the cases withONHD, displaying rounded-looking images of bubbles, sim-ilar to those obtained with SLO [4]. Specificity was very good(96.80 %), with good interobserver agreement (k00.818).

Sanders [17] was the first to describe the usefulness of theautofluorescence or pre-injection fluorescence technique in1967. Mustonen [2] found positive autofluorescence in79.7 % of 192 eyes with confirmed ONHD. Kurz-Levin [14]found positive autofluorescence in 47 % of 142 eyes withONHD. In our study, autofluorescence showed the highestvalues of sensitivity (88 %) and specificity (100 %) differen-tiating between ONHD and ODE, with excellent interobserveragreement (K00.957). The use of digital photographic equip-ment, which is becoming more and more sensitive, permitseasier detection of this phenomenon.

There are many publications that analyse different imagingtechniques in the diagnosis of ONHD; however, most studiesare retrospective. Kurkz-Levin [14] conducted a retrospectivestudy comparing autofluorescence, CT and ultrasound, whichshowed ultrasound to be the best diagnostic method. Pierro[18] prospectively studied 58 subjects with angioid streaks,detecting ONHD with ultrasound in 21.6 %, 13.8 % withophthalmoscopy and 10.3 % with autofluorescence.

Although there are publications that analyse sensitivity andspecificity in order to differentiate between optic nerve drusenand papilloedema with OCT [6], studies that analyse theseissues with monochromatic photography are yet to be found.

One limitation of this study was that suspected ONHDwas notassessed, as only the presence of visible drusen was analysed.

In conclusion, monochromatic fundus photography allowsus to differentiate between ONHD and ODE, with goodsensitivity and high specificity, enhancing sensitivity withregard to colour photography. The best results are obtainedwith autofluorescence and red filter study.

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