Herbort, Carl

Tugal-Tutkun, Ilknur

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Editorial: Laser flare (cell) photometry: 20 years alreadyCarl P. Herbort • Ilknur Tugal-TutkunReceived: 6 May 2010 / Accepted: 3 June 2010 / Published online: 1 July 2010 Springer Science+Business Media B.V. 2010Two decades ago, Sawa et al. [1] published an articleentitled ‘‘New quantitative method to determineprotein concentration and cell number in the aqueousin vivo’’ in the Japanese Journal of Ophthalmology.This work represented a milestone in the evolution ofmeasurement of intra-ocular inflammation. The laserflare (cell) photometer (LF(C)P) became commer-cially available in 1989–1990 and this technologypromoted flare from a qualitative parameter to theonly quantitative modality we have to measure intra-ocular inflammation.In 1954, the first grading system of anterior intra-ocular inflammation using slit-lamp observation of theaqueous humor was proposed by a group of cliniciansfrom the Proctor Foundation and had the merit ofstandardizing, at least in theory, inflammatory levels inthe anterior chamber [2]. Although the system wassupposed to set precise standards, it left a lot of space,especially as far as flare was concerned, for inter-observer and intra-observer variation, as it was asubjective system based on individual interpretation ofslit-lamp findings. As far as aqueous cells wereconcerned, the system was somewhat more precise asthe counting of cells with the slit-lamp is possible to acertain extent, but it remained, nevertheless, semi-quantitative at best. In 2004, uveitis specialists fromaround the world convened in Baltimore following theinvitation of a group of American clinicians to decideon a new standardization system for uveitis nomen-clature (SUN workshop) and, despite the fact that LFPhad been on the market for more than 10 years and itssensitivity and reliability had been proven withoutquestion, the SUN workshop took over the ProctorCriteria almost unchanged for the assessment of intra-ocular inflammation [3].Laser flare photometry (LFP) basically relies on thesame principles as slit-lamp evaluation of flare. As forslit-lamp flare measurement, there is an incoming lightbeam and the quantity of diffracted light, proportionalto the amount of cloudy matter in the aqueous humor(proteins), is measured. However the non-quantifiablepolychromatic incident beam of the slit-lamp has beenreplaced by a quantifiable laser beam in LFP and themeasuring device, the subjective human eye, isreplaced by an objective photomultiplier–photodetec-tor. Many studies were performed to show the immensesuperiority of this quantitative and objective method.In this issue a review article on LFP details the differentstudies that have been performed over the years [4].Laser flare photometry was, at first, thought to beespecially suited for clinical studies on intra-ocularC. P. Herbort (&)Inflammatory and Retinal Eye Diseases, Centrefor Ophthalmic Specialized Care (COS), CliniqueMontchoisi, Lausanne, Switzerlande-mail: carl.herb@bluewin.chC. P. HerbortUniversity of Lausanne, Lausanne, SwitzerlandI. Tugal-TutkunDepartment of Ophthalmology, Istanbul Facultyof Medicine, Istanbul University, Istanbul, Turkey123Int Ophthalmol (2010) 30:445–447DOI 10.1007/s10792-010-9384-xinflammation and indeed it was used in innumerablestudies. It allowed the evaluation of the anti-inflamma-tory power of numerous topically and systematicallyadministered substances and enabled comparisons to bemade between the substances. A selection of thenumerous studies performed can be found in the reviewarticle in this issue [4].However, it is in everyday uveitis practice thatLFP technology has proven most useful. LFP-mea-sured flare has become the only quantifiable param-eter for most cases of intra-ocular inflammation, inboth anterior and posterior segment inflammation, aslong as in the latter there is a minimum of associatedanterior chamber flare [5]. It was shown that LFP isnot only essential in the assessment and follow-upof acute inflammation but also in chronic disruptionof the blood–aqueous barrier. Even in the absence ofcells, LFP can detect active and treatable inflamma-tion, as was shown in a group of patients withjuvenile idiopathic arthritis-associated uveitis, wherea significant flare reduction after introduction ofmaximal therapy was demonstrated [6]. In this issue aclinical research article shows that LFP-measuredflare is superior to slit-lamp cell count for the follow-up of inflammation in acute cases of HLA-B27-related uveitis [7]. In essence, LFP is to uveitis whattonometry is to glaucoma: it allows measurement ofthe level of intra-ocular inflammation at any giventime point. An interesting article in this issue alsoshows that in uveitis it is possible to measure flare ineither dilated or non-dilated pupils, as no significantdifference was found [8]; however, for technicalreasons it is easier to measure flare in dilation.Today LFP is used in many foremost centresthroughout Europe and other parts of the world.Besides Europe, where LFP was rapidly integratedfor everyday practice in leading centres in France,Germany, Italy, UK, Scandinavia and Switzerland,clinical LFP studies have recently been performed inTurkey and China [9, 10]. In this issue Yang andcolleagues have followed the evolution of flare inBehc¸et’s uveitis [11].Although LFCP allows the quantification of cells orparticles in the aqueous humor, it is clinically lessrelevant. In clinical practice, the whole anteriorchamber is examined for the presence of cells usingthe slit-lamp. The instrument, however, only evaluatesa small volume, which makes it less reliable for cells asthe distribution of cells in the anterior chamber is lessdiffuse and uniform than proteins. This drawback,present in the FC-1000 model, has been attenuated inthe FC-2000 model which uses a larger measurementwindow. Nevertheless, this method allows objectivemeasurement and quantitative analysis of cellular orparticle numbers for the purpose of clinical studies.This editorial comment applies only to slit-lampLF(C)P photometers including the Kowa-FC-1000,Kowa FC-2000 and Kowa FM-500 models, allextremely reliable instruments. Unfortunately, theonly company producing this technology has aban-doned the instrument models constructed on theprinciple of the slit-lamp and today only producesone non-slit-lamp-based model, the Kowa FM-600.Although the new type of instrument has been testedand compared to previous models in study conditions,in everyday uveitis practice this new instrument is lesssuitable as it is fully automatic and does not allowmanual adjustments to orient the incident beam as canbe done in the slit-lamp construction principle. There-fore, no measurement can be obtained with the KowaFM-600 in many uveitic eyes, especially in the‘‘difficult’’ eyes where LFP is most required. More-over, first results in a European setting comparing thetwo types of instruments in everyday uveitis practicealso show that the Kowa FM-600 seems to be lessreliable, under-estimating flare in low flare conditions.It is difficult to understand why the manufacturersstopped producing extremely reliable models such asthe FM-500 measuring flare and the FC-2000 measur-ing flare and cells.When such fundamental revolutionary instrumentsbringing significant medical progress are put on themarket, the responsibility of the manufacturers goesbeyond purely commercial interests. They are respon-sible to the medical community and the patients toassure the continuity of such an indispensible tech-nology. We hope that slit-lamp models for LFP willagain be produced in the near future, leaving the non-slit-lamp models for studies where more standardizedconditions prevail.References1. Sawa M, Tsurimaki Y, Tsuru T, Shimizu H et al (1988)New quantitative method to determine protein concentra-tion and cell number in aqueous in vivo. Jpn J Ophthalmol32:132–142446 Int Ophthalmol (2010) 30:445–4471232. Hogan MJ, Kimura SJ, Thygeson P (1959) Signs andsymptoms of uveitis. I. Anterior uveitis. Am J Ophthalmol47(no.5, pt. 2):155–1703. SUN Working Group (2005) Standardization of uveitisnomenclature for reporting clinical data. Results of theFirst International Workshop. Am J Ophthalmol 140:509–5164. Tugal-Tutkun I, Herbort CP (2010) Laser flare photometry:a noninvasive, objective and quantitative method to mea-sure intraocular inflammation. Int Ophthalmol 30. doi:10.1007/s10792-009-9310-25. Herbort CP, Guex-Crosier Y, de Ancos E, Pittet N (1997)Use of laser flare photometry (LFP) to assess and monitorinflammation in uveitis. Ophthalmology 104:64–726. Herbort CP (2009) Laser flare photometry. In: Gupta A,Gupta V, Herbort CP, Khairallah M (eds) Uveitis: text andImaging. Jaypee Brothers, New Delhi, pp 28–497. Bernasconi O, Papadia M, Herbort CP (2010) Sensitivity oflaser flare photometry compared to slit-lamp cell evaluationto monitor anterior chamber inflammation in uveitis. IntOphthalmol 30 (in press)8. Ikeji F, Pavesio C, Bunce C, White E (2010) Quantitativeassessment of the effects of pupillary dilatation on aque-ous flare with chronic anterior uveitis using laser flarephotometry. Int Ophthalmol 30. doi:10.1007/s10792-010-9373-09. Fang W, Zhou H, Yang P (2008) Quantification of blood–aqueous barrier breakdown and anterior cells in Vogt–Koyanagi–Harada syndrome following immunotherapy. BrJ Ophthalmol 92:182–18510. Tugal-Tutkun I, Cingu K, Kir N et al (2008) A use of laserflare-cell photometry to quantify intraocular inflammationin patients with Behc¸et uveitis. Graefes Arch Clin ExpOphthalmol 246:1169–117711. Yang P, Fang W, Huang X, Zhou H, Wang L, Jiang B(2010) Alterations of aqueous flare and cells detected bylaser flare-cell photometry in patients with Behcet’s dis-ease. Int Ophthalmol 30. doi:10.1007/s10792-008-9229-zInt Ophthalmol (2010) 30:445–447 447123

Editorial: Laser flare (cell) photometry: 20years already

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Editorial: Laser flare (cell) photometry: 20years already

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