Ординатура / Офтальмология / Учебные материалы / Uveitis Text and Imaging Text and Imaging Text and Imaging 2009

Figure 1B: Original article by Sir John Tyndall. Introductory lines of Sir John Tyndall’s article on the effect of light on cloudy matters

Figure 2A: Tyndall effect. Illustration of the Tyndall effect or flare in a dark room through which beams of light ray are scattered by the dust in the air allowing to see the beam

Efforts were made to establish standardized rules to evaluate the level of inflammation in the anterior chamber. The system that was used with satisfaction for the last half century was put forward by Hogan, Kimura, and Thygeson at the Proctor Foundation in San Francisco. They established scores from 0 to 4 for both flare and cells that are shown on Table 1.2

In 2004 a panel of uveitis specialists came together to establish new universal criteria for the standardisation of uveitis nomenclature.3 These anterior chamber inflammation parameters were standardised anew but the system remained essentially the same with minor modifications of the “Proctor” criteria (Table 2). Such new standardisation criteria will not

Figure 2B: Tyndall effect (flare) in the eye. The phenomenon described by Sir John Tyndall occurs also in the aqueous humor where it is produced by back-scattering of light particles from proteins present in the aqueous humour. Influx of such proteins from the blood occurs due to the breakdown of the bloodaqueous barrier which is usually caused by inflammation but also other mechanisms

Table 1: The Proctor grading of aqueous flare

Grading of anterior chamber flarea

aReprinted with permission from : Kimura SJ, Thygeson P, Hogan MJ. Signs and symptoms of uveitis. I. Anterior uveitis. Am J Ophthalmol 1959;47:155-70.

Table 2: “New” grading of flare, SUN* workshop

Drawn from reference 3

*SUN = Standardisation of uveitis nomenclature

render the evaluation of uveitis more precise as long as they are still based on the same imperfect measurement methods and as long as they do not adopt new quantitative methods. Whatever standardisation

system based on slit lamp examination is used, the evaluation of these parameters remains in essence subjective as the human eye does not have the sensitivity to estimate slight contrast variations corresponding to subtle flare changes. Evaluation therefore will depend on the appreciation of each examiner with significant inter-observer and intraobserver discrepancies. Such a measurement of intraocular inflammation will be only qualitative as far as flare is concerned and semi-quantitative at most when dealing with cells.

Increased accuracy in the diagnosis of uveitis, progress in the knowledge of inflammatory mechanisms and improved therapy of inflammation resulted in more efficient management of intraocular inflammatory problems and was asking for more performing, quantitative modalities to evaluate and follow intraocular inflammation.

In 1988 Mitsuru Sawa and colleagues published an article entitled “New quantitative method to determine protein concentration and cell number in aqueous in vivo”.4 This was the result of several years of work performed together with the engineers of the Kowa company. At the start of this technology, it was thought to be only useful as a research tool but very quickly its utility in everyday clinical practice became obvious.

THE PRINCIPLE OF LASER FLARE (CELL) PHOTOMETRY

The laser flare (cell) photometer comprises a laser light beam (Helium-Neon or diode laser) of constant power (25 microW) and a diameter of 20 micrometers that is directed into the anterior chamber at an angle of 45o to the anteroposterior axis. At an angle of 90o to the incoming laser beam (45o to the anteroposterior axis) a photomultiplyer-photodetector unit is placed that detects back-scattered light from the incoming beam through a rectangle window measuring 0.3 × 0.5 mm (Figures 3A and B).

Two types of measurements are obtained. On one hand the instrument measures back-scattered light from small molecules such as proteins and this is called laser flare photometry. The measurement units of backscattered light from small molecules are number of photons per miliseconds (ph/ms). The amount of backscattered light is proportional to the concentration and

Figure 3A: Schematic diagram of measurement principle in laser flare photometry. The incoming light is in phase as it is produced by a laser beam. Instead of the human eye as the detector of back-scattered light the system contains a photodetector and a photomultiplyer (PMT) to exactly quantify the amount of photons that are back-scattered which are proportional to the amount of proteins which in turn are proportional the amount of inflammation

Figure 3B: Laser flare photometry : observer’s view during measurement procedure. The measuring window has to be placed in the darkest part of the anterior chamber at equal distance from the cornea and the crystalline lens anteriorposteriorly and between the middle and inferior third along the vertical axis. During the measurement sequence, the beam moves up and down from above the window, going through the measurement window and beyond. The photoncount above and below the window will acount for the background light which will be deduced from the light signal coming from inside the measuring window. Usually seven measurements are taken discarding the lowest and highest values and the five remaining measurements are averaged

size of proteins in the aqueous humour and is so indicating the level of inflammation.5,6

In experimental studies measuring dilutions of albumin with the laser flare photometer, flare was shown to increase proportionally to the concentration of albumin.4 The amount of back-scattered light is also proportional to the size of the protein molecule, increasing by a factor of 4 in relation to the radius of the molecule.7 Furthermore the sizes of the protein molecules found in the aqueous humour are proportional to the importance of the blood-aqueous barrier disruption.7

Some instruments measure back-scattered light from small molecules (proteins) as well as from larger particles such as inflammatory cells and the technique is then called laser flare-cell photometry. The instrument is able to distinguish light signals coming from small molecules (proteins) or from larger particles (inflammatory cells). The measurement units for particles/ cells are number of particles/cells counted in a volume of 0.075 mm3. The first dual measurement model put on the market was the FC-1000 (Figure 4). For this parameter the profile of the light curve is analysed and peaks of more intense scattering (corresponding to larger particles) are counted.4

In both measurement modes results were very reproducible.4,5,8,9 The coefficient of reproducibility showed a variation of less than 10% among different groups. Moreover the measurements are independent of the technician performing the laser photometry.9-10

THE HARDWARE FOR LASER FLARE (CELL) PHOTOMETRY

Presently Kowa Co. is the only manufacturer that builds laser flare (cell) photometers.

Just after the prototype models, Kowa comercialised the FC-1000 model which measured flare and cells but is no more available. As for all other models, the instrument was very precise and reliable for flare but less so for cells due to the small measurement volume. This was not optimal for cell measurement as the distribution can be heterogenous especially in low cell count situations. The second model put on the market was the FM-500 that had only the flare measurement mode, reflecting the problems noticed with the measurement of cells on the FC-1000 (Figure 5). The models presently on the market are the FM-500, a model measuring only anterior chamber flare, the FM-600 a small table model measuring also

Figure 4: Laser flare-cell meter FC-1000. The first model marketed by the Kowa company measuring both flare and cells in the aqueous. Cell measurement was, however, less precise than flare measurement, although highly correlated with flare, because the measurement volume (0.075 mm3) was small. The whole unit is voluminous coming in 2 parts and the laser used is a helium-neon laser

only flare, the advantage being that it is less costly. The FC-2000 model is measuring both anterior flare and cells. The latter model gained in precision for the measurement of cells as the measurement volume was increased to 0.5 mm3.

PHYSIOLOGICAL FLARE VALUES AND VARIATIONS

In the normal individual the mean flare value amounts to 4.7 ± 1.5 ph/ms, but after the age of 30 it increases slightly but gradually with age, reaching 5 ± 2 ph/ms in the 55-65 years age group and a flare of 7 ph/ms still being normal for an individual aged 70 years.11,12 Flare values are not influenced by the local application or intravenous injection of fluorescein.13 An increase of flare follows the administration of a dose of 500 mg of acetazolamide, the topical instillation of analogues of acetazolamide and the topical instillation of the selective alpha-2 agonist apraclonidine.14-16 The mechanism is a decrease of aqueous humour production that becomes more concentrated. The administration of a mydriatic produces a decrease of aqueous flare by 11-20% in normal individuals.17 This might be

Figure 5: Laser flaremeter Kowa FM-500. This was the second machine put on the market by Kowa Co. and measures only aqueous flare. Examiner is on the right. The laser used is a diode laser and the whole unit is more compact

due to a better positioning of the measurement window away from the reflecting structures. Therefore, it is advisable to perform laser flare photometry 30 minutes after the instillation of mydriatic drops. The instillation of topical prostaglandin F2 alpha analogues has no effect on aqueous flare in human eyes, whereas prostaglandin E2 instillation causes an increase of flare in rabbit eyes.18,19 Most of these variations, although statistically significant, are however not clinically relevant and become negligible in inflamed eyes. A recent study has shown that in pathological conditions measurement of flare in non-dilated and dilated pupils did not differ significantly (Pavésio CE, personal communication).

CORRELATION BETWEEN SLIT LAMP FLARE EVALUATION AND LASER FLARE PHOTOMETRY

Several studies were performed, correlating flare evaluation using the slit lamp with flare measured by laser flare photometry. All the studies clearly showed that both measurement methods were highly correlated.20-24 However, in slit lamp flare evaluation

there was a high intra-observer and inter-observer variability, making it a fairly unreliable measurement parameter. Moreover, when comparing the two scales it is obvious that slit lamp flare evaluation totally lacks sensitivity when compared to laser flare photometry. In one study it was shown that the clinical grade of 1+ flare corresponded to 28.3 ± 4.8 photometry units and 3+ clinical flare corresponded to 82 ± 5 ph/ms. By consequence a 4+ clinical flare corresponds to laser flare photometry values from 150-1000 ph/ms. Therefore, any new standardisation system of uveitis nomenclature in reporting clinical data for study purposes should not only recommend laser flare photometry as the method of choice to measure aqueous flare but make it mandatory.

PATHOLOGICAL CONDITIONS CAUSING FLARE INCREASE

Numerous studies have been performed looking at pathological conditions. We will only cite several of them and then concentrate on the use of laser flare photometry in uveitis and inflammatory diseases.

Flare is more elevated in eyes with pseudoexfoliation syndrome for which a mean flare of 12.3 ± ph/ms was measured that correlated with an increase of aqueous proteins.24 Flare was also found to be more elevated in the contralateral eye, indicating that there is probably a subor pre-clinical stage of pseudoexfoliation.25

Flare was found to be elevated also in retinitis pigmentosa, another degenerative condition. Mean flare values were 9.65 ph/ms with the highest values in patients with a concomitant cystoid macular oedema.26 Flare values were shown to be elevated in diabetic patients even without diabetic retinopathy.27 In patients with diabetic retinopathy flare values were correlated with the severity of retinopathy.28

In central vein occlusion flare was shown to be elevated to 12.3 ± 6.7, an increase that was highly significant when compared to the control eye.29 Such a subclinical but significant flare rise indicates increased permeability of intraocular vessels and might explain why intraocular anti-VEGF therapy in central or branch retinal vein occlusion is so effective. In choroidal melanoma the diseased eye showed a significant increase of flare when compared to the

contralateral eye. Moreover flare level was correlated with the size of the tumour.30 In all these examples and in many more situations not reported here, laser flare photometry has allowed to show subclinical alterations in the blood-ocular barriers identifying subtle pathological changes that could not have been recorded otherwise. In all these studies the extreme sensitivity of laser flare photometry even for preponderantly posterior conditions was demonstrated.

THE ROLE OF LASER FLARE

PHOTOMETRY IN CLINICAL STUDIES

ON INTRAOCULAR INFLAMMATION

The exquisite sensitivity of laser flare photometry to detect very low, subclinical alterations of the bloodocular barriers and to detect imperceptible changes at such subclinical flare levels, make this technology unavoidable to conduct clinical trials investigating anti-inflammatory therapy on intraocular inflammation or to study the effect of any procedure or intervention on intraocular inflammation.

With the advent of LFP it became possible to compare the impact of different surgical techniques on intraocular inflammation in cataract or glaucoma surgery.31

It was established that cataract surgery using small incision with implantation of a foldable lens was producing less inflammation than implantation of a rigid lens through a larger incision.32 Laser flare photometry also showed that post-surgical inflammation was proportional to the duration of surgery.33 The use of acetyl-choline was shown to significantly decrease postoperative flare.34 We showed that in opposition to what was thought, removal of the secondary cataract in uveitis was not increasing the level of inflammation. Inflammation was significantly lower in the long term after surgery when compared to mean pre-surgery levels.35 Mean flare, mean maximal flare taking inflammation peaks and mean number of relapses were significantly lower in an observation period of one year after cataract surgery when compared to a mean observation period of 3 years before the surgery (Figure 6).

In glaucoma surgery it was shown that nonpenetrating filtering surgery (deep sclerectomy) generated significantly less post-surgical inflammation

Figure 6: Laser flare photometry study on the impact of cataract surgery on inflammation in uveitis patients. LFP showed that mean preoperative flare was significantly lower in the period after surgery, using rigid PMMA lenses with a lower inflammation using heparin coated lenses (originally published and reproduced from: Can J Ophthalmol 1998;33:264-9)

than standard trabeculectomy.36 Surgical inflammation following deep sclerectomy in uveitic glaucoma was also shown by LFP to be well under control with this procedure.37

The impact of laser interventions on intraocular inflammation has also been studied.

Argon laser trabeculoplasty produces a significant flare increase after 6 hours which peaks at 48 hours with a mean flare level of 21±4 ph/ms38,39 (Figure 7). This inflammatory reaction can be completely abolished when nonsteroidal anti-inflammatory drops are given.40 However nonsteroidal drops should be given for at least five days as rebound inflammation was noted in 2 cases after discontinuation of therapy in a 4-day regimen. Trabeculoplasty performed with Nd-YAG laser causes a slightly lower flare with a similar effect on intraocular pressure.41 Retinal argon laser photocoagulation for central retinal vein occlusion causes a significant flare increase that returns to pre-laser values within one month.42 Retinal photocoagulation in diabetic retinopathy caused a significant increase of flare from 3 to 48 hours after laser intervention with a longer duration of flare increase in eyes with brown irises.43

We will only cite a few of the numerous studies performed on the assessment of anti-inflammatory drugs or drops mainly in post-surgical intraocular inflammation. Such studies are nowadays unthinkable without the use of LFP. Thanks to LFP, we were able

Figure 7: Laser flare photometry study on the effect of diclofenac sodium drops on the inflammation after laser trabeculoplasty. LFP showed that inflammation was completely abolished by diclofenac drops when compared to the placebo group. (* = p < 0.05; § = p < 0.01) (originally published and reproduced from: Arch Ophthalmol 1993;111:481-4)

Figure 8: Laser flare photometry study on the effect of diclofenac sodium drops on the inflammation after cataract surgery with lens implantation. Even though the diclofenac group had a higher level of inflammation on day D1, inflammation level was significantly lower on days D3-4 and D12-14 (originally published and reproduced from: Acta Ophthalmol Scand 2000;78:421-4)

to show for cataract surgery, that nonsteroidal antiinflammatory drops (NSAIDs) were as efficient as corticosteroid drops to control post-surgical inflammation. We first showed that topical NSAIDs given for post-surgical inflammation had an additional effect to topical corticosteroids.44 We further showed that NSAIDs were at least as good as corticosteroid drops in the treatment of post-surgical inflammation45,46 (Figure 8). The radical effect of diclofenac sodium on post-trabeculoplasty inflammation has already been discussed above.40

THE UTILITY OF LASER CELL

PHOTOMETRY IN MEASURING

ANTERIOR CHAMBER PARTICLES (CELLS)

The gain of precision obtained by the laser cell photometry measuring anterior chamber particles (cells) over slit lamp is less spectacular than laser flare photometry measuring anterior chamber flare. In case of flare evaluation the human eye is absolutely unable to distinguish subtle flare changes. The machine on the other hand is able to record minute changes in flare levels. Such a precision is possible because of the uniform concentration of proteins in the aqueous humour. As far as cells are concerned, the human eye can distinguish individual cells within the slit lamp beam shining through the anterior chamber making a

semi-quantitative measurement of anterior chamber cells possible with the slit-lamp although tedious for the examiner. Because the measurement volume in the first commercialised laser flare-cell meter (KowaFC- 1000) was very small (0.075 mm3) and because the distribution of cells is not always uniform in the anterior chamber, laser cell photometry is somewhat less precise when compared to laser flare photometry. In one situation we showed, however, that laser cell photometry was more useful than laser flare photometry. In a study analysing anterior chamber flare and cells after Nd:YAG capsulotomy we showed that flare rise was minimal and mostly not significant, whereas the increase of particles (probably coming from capsular debris) was significant and probably explained the intraocular pressure rise that occurred in 20% of patients with which it is correlated47 (Figures 9A and B). It is probable that with the new laser flarecell photometer (Kowa FC-2000) anterior chamber cell measurement will also reach the high precision obtained for the measurement of aqueous flare because the measurement volume is much larger (0.5 mm3).

LASER FLARE PHOTOMETRY IN UVEITIS

Although laser cell photometry in uveitis certainly represents a gain over slit lamp assessment of cells in the anterior chamber because it is quantitative, the

Figure 9A: Laser flare-cell photometry study on the level of flare and particles after Nd:YAG capsulotomy; graph showing the evolution of flare. The impact on anterior chamber flare by Nd:YAG capsulotomy is producing a minimal increase of flare (originally published and reproduced from: J Cataract Refract Surg 1992;18:554-8)

Figure 9B: Laser flare-cell photometry study on the level of flare and particles after Nd:YAG capsulotomy; graph showing the evolution of aqueous particles. LFCP showed that there was a significant increase in number of particles after Nd:YAG capsulotomy probably generated by capsular debris in solution. This increase of particles was directly related to pressure rise possibly indicating transient clogging of the trabecular meshwork (originally published and reproduced from: J Cataract Refract Surg 1992;18:554-8)

improvement it brought for the appraisal of intraocular inflammation is not as determining a progress as laser flare photometry for the reasons discussed in the previous paragraph and only the latter will be discussed here.

The potential of laser flare photometry for the management of uveitis was very quickly evident. It is now accepted that flare measured by laser flare

photometry is the only objective and quantitative parameter to measure intraocular inflammation both in acute and chronic inflammation.

At first LFP was used to determine the inflammatory profiles of well defined uveitis entities. Upon regular use in some uveitis centres, it became obvious that it would be a very reliable parameter in clinical practice to precisely establish the exact level of intraocular inflammation as well as a precise mean to monitor the evolution of inflammation and the impact of therapeutical intervention. In certain cases it would also contribute to the diagnosis by showing the absence or the presence of a therapeutic response well before other clinical signs showed noticeable changes.

FLARE (MEASURED BY LFP) IS THE ONLY QUANTITATIVE PARAMETER TO MEASURE INTRAOCULAR INFLAMMATION

LFP-flare is More Sensitive than Slit lamp Flare and Slit lamp Cells Measurement in the Aqueous in Acute Inflammation

The scale of laser flare photometry going from 0 to 1000 ph/ms, when compared to slit lamp flare and slit lamp cell scales going from 0-4 already allows to understand the incomparable degree of precision of laser flare photometry. In low flare situations (flare < 40 ph/ms) it is absolutely impossible for the human eye to detect a difference of beam intensity in the anterior chamber of less than 10-15 ph/ms, whereas laser flare photometry is giving the exact number of back-scattered photons. This difference of sensitivity is even more pronounced in high flare situations (> 100 ph/ms). We conducted a study on the respective sensitivities of LFP-flare measurement, slit lamp flare recording and slit lamp cell recording in the anterior chamber in an acute inflammatory condition such as HLA-B27 related acute anterior uveitis.48 Forty-nine episodes of HLA-B27 related acute anterior uveitis in 40 patients were followed from presentation up to 3 months, by recording LFP flare, slit lamp aqueous flare, slit lamp aqueous cells as well as usual clinical signs. All three parameters were strongly correlated. Flare measured by laser flare photometry was however, significantly more sensitive to assess decrease of anterior chamber inflammation than slit lamp assessment of both flare and cells with a 50%

reduction respectively on day 4 for LFP, day 7 for slit lamp flare and day 14 for slit lamp cells.

This study showed that laser flare photometry was superior to slit lamp assessment of both flare and cells to monitor anterior chamber inflammation. By becoming a quantitative, objective and maximally sensitive parameter, LFP-flare rather than slit lamp flare or cells, should be considered the reference parameter to monitor anterior chamber inflammation.

LFP-flare is More Relevant than Slit Lamp Aqueous Cell Count to Detect Active Inflammation in Chronic Disease Also

Up till now it was universally admitted as much in textbooks as in articles that in chronic disease, only the presence of anterior chamber cells was an indicator of active inflammation while flare was attributed to chronic irreversible breakdown of the blood-aqueous barrier. Despite the advent of laser flare photometry in the early nineties of last century this erroneous axiom was not put in question since. It is true that in chronic inflammation, the presence of aqueous cells indicates active inflammatory activity. It is also true that in chronic disease, flare is produced by a chronic breakdown of the blood-aqueous barrier on which anti-inflammatory therapy does not seem to have an impact. The latter notion is, however, only partially true and it is now known that an appreciable part of what was thought to be chronic flare is in fact due to active inflammation, a fact that could not be detected without the help of laser flare photometry. Indeed, in high flare states (> 100 ph/ms) usually present in chronic inflammation, the human eye cannot detect a decrease of flare even as high as 40 ph/ms and therefore cannot verify the effect of anti-inflammatory therapy. We analysed a group of patients with JIA associated uveitis that had longstanding chronically evolving disease without the presence of a significant amount of aqueous cells. The patients all had a flare of > 3+ as judged by slit lamp examination. In the absence of cells, these patients were under minimal treatment for ocular inflammation at presentation “because there was no active inflammation”. Patients were put at entry under maximal therapy including topical corticosteroid drops, systemic corticosteroids and systemic immunosuppressives in case of very high flare values. Mean flare value at presentation was

176.03 ± 98.36 ph/ms which was reduced to 76.8 ± 69.87 ph/ms after maximal therapy as indicated above. The difference of 176 to 77 ph/ms (= 99 ph/ms) represented the active part of inflammation on which therapy had an impact. Of course the human eye would be incapable to perceive let alone to quantify such flare reductions in high flare states. Therefore in centres using laser flare photometry this technology makes flare the preponderant and only quantitative parameter to evaluate active intraocular inflammation also in chronically evolving disease.

INFLAMMATORY PROFILES OF DIFFERENT UVEITIS ENTITIES

HLA-B27 Related Acute Anterior Uveitis

The mean inflammatory profile in HLA-B27-related acute anterior uveitis (AAU) was established in a study that included 44 patients receiving standard therapy.49 Therapy consisted of 1% prednisolone drops given hourly at presentation or more frequently when severe inflammation was present, progressively tapered after 3 days the time and pace of tapering depending on the evolution of inflammation. If posssible dilatation was achieved in-office with a combination of mydriatics and maintained with short-acting mydriatics such as tropicamide drops Q6-8 daily thereafter. At night corticosteroid ointment was given. Mean initial flare in HLA-B27 related uveitis was 166 ± 22 ph/ms (range 11-787 ph/ms) at presentation, which was significantly higher than mean flare in a healthy control group of 88 patients (4.7 ± 0.16 ph/ms) (Figure 10A).

Using the described standard therapy, flare decreased by 50% between day 1 and day 2 and by 90% by day 8. The mean duration of an episode (drop of flare below the 8 ph/ms level without rebound inflammation within 2 weeks) was 18 days ± 15 standard error of the mean (SEM).50 Absence of flare decrease or even flare increase during more than 48 hours in a high flare state (> 100 ph/ms) was a criterion to give additional orbital floor hydrosoluble corticosteroid injections (betamethasone, 4 mg). Such injections were necessary in 16% of patients. In order to document the effect of additional orbital floor betamethasone injections, flare measurements were performed at 1, 2, 3, 6, 10, 24, 36, 48 and 72 hours after injection. A 50% flare reduction was achieved 10 hours

Figure 10A: Inflammatory pattern in HLA-B27 related acute anterior uveitis (AAU) studied by LFP. Forty-four cases of HLAB27 AAU receiving a standardised topical treatment were followed by LFP to determine the evolution of aqueous flare from presentation to the end of the episode. Under standard therapy a 50% flare reduction was obtained between days D1- 2 and a 90% reduction was obtained at day D8 (originally published and reproduced from: Ophthalmology 1997;104: 64-72)

Figure 10B: Effect of additional periocular injection (orbital floor) of hydrosoluble corticosteroids in patients not responding to standard topical therapy. Additional periocular steroids were extremely effective in cases resistant to topical steroid drops with a 50% reduction of flare obtained already after 10 hours (originally published and reproduced from: Ophthalmology 1997;104:64-72)

after orbital floor betamethasone injection and an 80% reduction was obtained 72 hours post-injection (Figure 10B). In this study it became evident that LFP was especially useful in adjusting therapy with, on one hand the clear necessity for additional orbital floor corticosteroid injections when photometry showed that flare was resistant to standard therapy and on the other hand, abstention of injections when LFP showed decrease of flare that could not yet be seen clinically.

In individual cases of HLA-B27 acute anterior uveitis with high flare values only LFP is able to verify whether inflammation is responding to therapy or

whether it is resistant and needs additional periocular corticosteroids. In Figure 11, we show two cases with similar initial inflammation (Figures 11A and B) for whom LFP clearly shows rapid decrease of flare in one case and persistent high flare in the other case (Figure 11C).

Fuchs’ Uveitis

In Fuchs’ uveitis laser flare photometry measurements showed that mean flare values did not increase

Figure 11A: Individual case of HLA-B27 related AAU showing synechiae and fibrin. LFP failed to show the expected decrease of flare even after 48 hours (yellow line on figure 11C) which prompted the clinician to perform an orbital floor injection of hydrosoluble corticosteroids with a prompt response of flare

Figure 11B: Individual case of HLA-B27 related AAU showing synechiae and fibrin identical to the case shown in Figure 11A. LFP showed prompt response of flare to standard topical therapy with a drop of flare by 75% after 12 hours (red line on graph of Figure 11C) indicating that the case has a favourable evolution without additional periocular steroid injections needed

Figure 11C: Graph showing evolution of aqueous flare in individual cases of HLA-B27 related AAU. At flare levels above 100 ph/ms it is impossible for the human eye to determine change of flare using the slit lamp. LFP allows to determine flare changes already a few hours after the start of therapy and shows clearly that one patient is responding very well to topical therapy (red line), whereas the other one with a similar clinical presentation is not responding to standard topical therapy (yellow line)

significantly with time and remained constant over months or years (8.62 ± 4.2 ph/ms at presentation versus 8.45 ± 4.3 ph/ms at the end of follow-up).51 This indicates that the blood-aqueous barrier disruption does not progress in Fuchs’ uveitis despite abstinence from anti-inflammatory therapy. Fuchs’ uveitis is among the most underdiagnosed uveitis conditions. One reason for that is that the disease was first described in a Caucasian population by Fuchs in Vienna where heterochromia is a prominent feature of the disease. Until very recently and even today the name of the disease, “Fuchs’ heterochromic cyclitis” included this clinical sign. Heterochromia being absent in brown irides, the disease is widely underdiagnosed in populations with brown irides. The other reason why the diagnosis of Fuchs’ uveitis is so often missed comes from the fact that, in the literature including published articles and textbooks, Fuchs’ uveitis is known as an anterior uveitis. The fact that vitritis, a feature well described in the original publication by Fuchs, is the single most frequent feature of the disease, is not well known and well publicised.51 Therefore when the clinician detects vitritis in a Fuchs patient he is puzzled and excludes the diagnosis thinking more of intermediate uveitis. In a group of 79 patients with Fuchs’ uveitis seen at the Centre for Specialised Ophthalmic Care in Lausanne, Switzerland

a secondary referal unit, the proportion of non-diagno- sed cases of Fuchs’ uveitis was 75% (59/79 patients) and a large proportion of patients were under systemic corticosteroid therapy (26/59 patients, 44%) and even under systemic immunosuppressants (13.5%). In these cases LFP was extremely useful because it showed that after discontinuation of topical and/or systemic antiinflammatory therapy, there was no significant rise of LFP flare values.

JIA Associated Uveitis

In textbooks and ophthalmic literature on the whole it is commonly written that only anterior chamber cells are the hallmark of active intraocular inflammation in chronic disease. Uveitis associated with juvenile idiopathic arthritis is characterised by a protracted and chronic course and analysis of the anterior chamber in longstanding inflammation usually shows a pronounced flare and very few cells. Because cells are absent, the common belief is that no active inflammation is present. Laser flare photometry allowed us to show that in minimally treated patients judged to have no active inflammation because there were no aqueous cells, the introduction of a maximal therapy produced a substantial decrease of LFP-flare. It was also shown that an initial high level of flare and a limited restitution of the blood-aqueous barrier was correlated with a deleterious evolution. A group of patients with a deleterious evolution and complications were found to have a much higher mean initial flare of 184.98 ± 97.04 ph/ms with a suboptimal reduction after maximal therapy to 106.1 ± 82.31 ph/ms (minus 42.5%) as compared to the group with favourable outcome whose initial flare was much lower (69.81 ± 89.64 ph/ms) and responded well to maximal therapy. LFP-flare decreased to 24.94 ph/ms ± 21.37 indicating a much better restitution of the bloodaqueous barrier with a decrease of 65% of aqueous flare. Laser flare photometry allowed to justify agressive maximal therapy on one hand and avoided to undertreat patients, justifying maintenance or even increase of therapy as long as a decrease of flare was obtained. On the other hand, LFP in more benign cases avoided unnecessary overtreatment in those cases where flare was shown to be stable or to decrease. Similar findings were published in a more recent paper on chronic uveitis in children.52 The authors found that