Vetenskap 8 16

VETENSKAP # 8–2016 www.optikbranschen.se

Hösten kommer med förändringar

D

å är vi tillbaka på jobb efter en sommar som jag hoppas gett både lugn och roliga minnen. Det behövs när hösten kommer och kanske särskilt denna höst som kommer med nyheter för oss optiker. Socialstyrelsen har beslutat att optiker med särskild behörighet har rätt att rekvirera vissa diagnostiska läkemedel, detta gäller från 1 september. Läkemedelsverket har dock i skrivande stund ännu inte fått sitt regelverk i tryck, mer om detta finns att läsa på Optikerförbundets hemsida/intranätet och respektive myndighets sida. Det innebär att många år arbete till slut är i hamn.

Vad passar då bättre än att här presentera ett examensarbete som utfördes under året på Magisterutbildningen på KI, angående förändringar av IOP vid användande av olika pupillvidgande ögondroppar. Det är ett spännande arbete att läsa och högaktuellt i dessa dagar.

Den andra artikeln är via länk och där har förändringar på bland annat främre kammaren undersökts vid förändringar på pupillstorleken.

Personer med trång kammarvinkel, normal kammarvinkel och misstänkt trång kammarvinkel har jämförts med varandra. Båda dessa artiklar visar på hur IOP kan förändras när pupillen ändrar storlek och att ögat ska kontrolleras innan diagnostiska droppar används. Även om det bara är en liten ögondroppe så påverkas ögat och negativa effekter kan uppkomma.

Att kunna utföra dilatation av pupillerna vid undersökningar gör det lättare att bedöma eventuella förändringar och ger säkrare beslut, men kunskapen måste finnas om vad det är man ser. En sak som vi alla optiker ser är cataract, även om de olika typerna kan vara lättare att se efter dilatation.

Men här kan många erbjuda ett bättre omhändertagande. Många sjukhus inom vissa landsting har extremt långa väntetider, men vi kan remittera även utanför vårt eget landsting. Min rekommendation är att använda www.vantetider.se där kan man se förväntade väntetider för t.ex. cataractoperation och remittera dit där väntetiden är kort och till en ort som passar patienten. Även om de avböjer att resa så vet de att möjligheten till snabbare åtgärd finns, patienten är nöjd.

Att vidareutbildning är viktigt vet alla och även om höstens kurser nu har startat och du inte har anmält dig och påbörjat någon av dessa, så finns chansen till nästa år. Fatta beslutet redan nu att till våren söka den vidareutbildning som passar dig.

Optikerförbundets egna kurser är i en fas av vidareutveckling fler kurser kommer upp efter hand. Frågor för CET poäng kopplade till artiklarna finns som vanligt på Optikerförbundets hemsida och hela artikeln samt länk på Optikbranschens hemsida.

Trevlig läsning och njut av sensommaren!

CATARINA ERICSON

n Artikel 1: Två dilaterande droppars påverkan på det intraokulära trycket – jämförelse mellan en enkel substans och en kombinationsdroppe n Artikel 2: Biometrisk utvärdering av förändringar i främre kammaren efter fysiologisk pupilldilatation utförda med Pentacam och optisk koherens tomografi (OCT)

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Catarina Ericson är OPTIK:s vetenskapsredaktör. Hon är MSc i Klinisk Optometri och Leg Optiker. e-post: catarina@c-optik.se

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Redaktörens kommentar:

Introduktionen ger en bra påminnelse om vad de olika dropparna har för verkan. Resultatdelen och diskussionsdelen är intressanta.

Comparison of a single agent vs. a combination agent – effect on intraocular pressure Författare: EMMA HARALDSSON Karolinska Institutet, Magisterutbldning

BACKGROUND Topically administered mydriatic and cycloplegic drugs are routinely used in clinical practice today. It is a wellknown fact that these agents can cause an elevation of the intraocular pressure (Harris, 1968; Hancox et al., 2002; Kim et al., 2012; Atalay et al., 2015a; 2015b).

As early as in the 1960s Laurence S. Harris wrote that the elevation of intraocular pressure (IOP) caused by mydriatics and cycloplegics had been long known in certain eyes. Observations in clinical practice had shown this elevation frequently in the glaucomatous population. Harris found a significant elevation of IOP in 23% of glaucoma patients, while the prevalence in normal eyes was only 2% (Harris, 1968).

In individuals without glaucoma, the mean change in IOP caused by cycloplegics or mydriatics varies between +1.85 mm Hg and -1.2 mm Hg (Christensen and Pearce, 1963; Harris, 1968; Hancox et al., 2002; Pukrushpan et al., 2006; Qian et al., 2012; Kim et al., 2012; Oltulu et al., 2015; Atalay et al., 2015a; 2015b). The risk of having a significant elevation of the IOP is lower in individuals without glaucoma. Studies have shown a prevalence of 2-11% (Harris, 1968; Hancox et al., 2002; Tan et al., 2009; Qian et al., 2012; Atalay et al., 2015a; 2015b). In opposite, a decrease in IOP post-dilation is frequent in this patient group with a prevalence of 25-50% (Christensen and Pearce, 1963; Qian et al., 2012; Oltulu et al., 2015; Atalay et al., 2015a; 2015b).

Correlations between IOP change and other parameters, such as pre-dilation IOP, anterior chamber angle, anterior chamber depth, anterior chamber volume, pupil diameter, central corneal thickness, age, sex, ocular medications, ethnicity, iris colour and lens status have been investigated in previous studies. No clear correlations have so far been established (Harris, 1968; Hancox et al., 2002; Pukrushpan et al., 2006; Qian et al., 2012; Atalay et al., 2015a; 2015b). It has been found that aphakic eyes can experience a dramatic decrease in IOP post-dilation (Salam et al., 2005).

Attempts to explain why an individual experience an elevation or decrease in IOP have been made, but the mechanisms are not yet certain. An increase in IOP can be explained by a significant iris pigment liberation, which causes obstruction of the trabecular meshwork and reduces aqueous humour outflow (Shihadeh et al., 2011). A reduction in IOP has been explained by a drugs effect on the ciliary tonus/accommodation. When the muscle relaxes, the uveoscleral outflow increases and if this increase is greater than the decrease in trabecular outflow, the result is a reduction in IOP. Drugs with a strong cycloplegic effect can therefore be assumed to lower IOP more frequently than mydriatic drugs (Christensen and Pearce, 1963; Harris, 1968; Toris et al., 1995; Alm and Nilsson, 2009).

Both mydriatic and cycloplegic drugs could have local and systemic side-effects other than significantly eleva-

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ted IOP. These side-effects are rare but include hyperemic rashes, redness around the eyes, fever, tachycardia, hypertension, tremors, hallucinations, disorientation, drowsiness, nausea, fatigue, lack of muscle controll and even anaphylactic chock (Jones and Hodes, 1991; Mirshahi and Kohnen, 2003; Rosenfield et al., 2009; Tayman et al., 2010). In order to avoid the unwanted effects, precautions can be taken. A thorough history is of greatest importance, so that the impact of any disease, current medication or previous experience can be taken into consideration.

The aim of this study is to compare the change in intraocular pressure caused by two different dilating drugs. One is a single agent mydriatic drug, and the other a combination agent cycloplegic drug. The study aims to investigate the drugs’ separate effect on IOP, and compare them to each other. To the author’s knowledge, no previous study on pre- and post-dilation IOP has been made on the combination agent drug, which is frequently used in clinical practise in Sweden. Nor has a comparison of the change in IOP caused by these two different types of drugs been made. The results of this study were expected to be consistent with the theories on why individuals experience an elevation or decrease after dilation with different dilating agents.

MATERIALS AND METHODS Participants enrolled in this study were patients at Karolinska Institutet’s optometry-clinic located at St. Erik’s Eye Hospital in Stockholm, Sweden. Optometrists studying at the Master’s programme in Clinical Optometry conducted all the exams. Prior to dilation, all patients were examined and interviewed to determine if they were suitable participants. In some patients only one eye was included.

The drugs used in this study were Tropikamid 0.5% and Cyklopentolat-fenylefrin 0.75%+2.5%. Tropicamide is an anticholinergic drug that dilates the pupil by blocking the receptors on the iris sphincter muscle, i.e. preventing miosis by relaxing the sphincter muscle.

Cyclopentolate works in the same way but has a greater impact on the receptors in the ciliary body muscle, which gives it a stronger cycloplegic effect. The second agent in

the combination drug is phenylephrine. It has difficulties generating enough dilation on it’s own and works best combined with an anticholinergic agent. Phenylephrine is an alpha1-adrenergic agonist that binds to the receptors on the dilator muscle. It activates the muscle and produces mydriasis in the same way as the sympathetic nervous system naturally does, through emotions like fear, anger or pleasure (Rosenfield et al., 2009).

The exclusion criteria were set according to the contraindications of the drugs. Exclusion criteria were: pre-dilation IOP > 25 mm Hg, anterior chamber angle < 2 (estimated with van Herick’s method), diagnosed with glaucoma or ocular hypertension, currently on IOPlowering drug, pregnant or breastfeeding and hypersensitivity to any component in the drug.

The purpose of the patient’s visit as well as exclusion criteria determined which drug the patient received. One drop was administered topically in the conjuctival sac of each eye, and only when it did not generate dilation, another drop was given. No patient received more than 2 drops in each eye.

Most patients included in this study had a complete eye-health-exam at the clinic, but a small group were scheduled with an ophthalmologist and retinal surgeon.

This group of patients had an optometry-exam (including dilation) prior to their meeting with the ophthalmologist, and where all given the combination agent drug. After their ophthalmology-exam, their post-dilation IOP was measured.

IOP was measured pre- and post-dilation with Reichert 7CR Ocular Response Analyzer. This non-contact tonometer calculates the intraocular pressure of the eye by measuring corneal response to soft air puffs delivered onto the eye. Force-in and force-out applanation is detected in an optical detector system by the reflection of light from the cornea. Based on the force-in/forceout applanation pressure, the machine mathematically calculates a corneal compensated intraocular pressure (IOPcc). The IOPcc is designed to take the biomechanical properties of the cornea, such as corneal visco-elasticity and thickness into consideration. The measurement result is scored 1-10, and a score lower than 7 indicated a redo. Three measurements were taken on each eye and

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the displayed result was an average of these, provided that they all had a score within 1 number of the highest measured score. If a measurement had a score lower than 1 number of the highest, it was discarded.

Post-dilation IOP was measured on average 42 minutes after the drug was administered, although the time could vary quite a bit depending on what kind of exam the patient received (42 ± 15 min).

The study was conducted in accordance with the tenants of the Declaration of Helsinki. All participants were informed prior to their visits, that they would be examined at an educational clinic where all results could be used in studies or for educational purposes. All participants gave their consent.

RESULTS The study included 273 eyes of 158 subjects. Of these, 115 subjects (214 eyes) received the single agent and 43 subjects (59 eyes) received the combination agent drug.

The mean pre-dilation IOP for eyes dilated with Tropikamid was 15.49 ± 3.08 mmHg, and post-dilation IOP was 15.21 ± 3.30 mmHg. This change was statistically significant (p=0.0427). The mean pre-dilation IOP for eyes dilated with Cyklopentolat-fenylefrin was 15.85 ± 3.22 mmHg, and post-dilation IOP was 15.22 ± 3.35 mmHg. This change was also considered statistically significant (p=0.0187). The pre-dilation and post-dilation IOP with p-values are shown in Table 1.

Table 1. Mean pre- and post-dilation IOP

Table 2. Mean change in IOP caused by the two drugs

The mean change in IOP caused by Tropikamid was 1.78 ± 1.64 mmHg and when divided into elevations (positive values) and decreases (negative values), the mean change was -0.29 ± 2.41 mmHg. For Cyklopentolat-fenylefrin the mean change in IOP was 1.64 ± 1.27 mmHg and when divided into elevations and decreases, the mean change was -0.63 ± 1.99 mmHg. These changes in IOP did not significantly differ (p=0.9732, p=0.2632). Table 2 shows the mean changes in IOP caused by the two drugs.

A change in IOP post-dilation of >±2 mmHg was observed in 58 of the 214 eyes dilated with Tropikamid.

This is equal to 27.1% (Figure 1). Of these 58 eyes, 19 were elevations and 39 were decreases, which is equal to 32.8% and 67.2%. Cyklopentolat-fenylefrin was given to 59 eyes, and 17 of these had a change in IOP postdilation of >±2 mmHg. This is equal to 28.8% (Figure 2).

The distribution of elevations and decreases was 5 and 12, which is equal to 29.4% and 70.6%. This means that Tropikamid caused an elevation of >2 mmHg in 8.9% of all eyes and a decrease in 18.2%, while Cyklopentolatfenylefrin caused an elevation in IOP in 8.5% and a decrease in 20.3% (Figure 3).

A change in IOP post-dilation of ≥5 mmHg was observed in 17 of the eyes dilated with Tropikamid, which is equal to 7.9%. The distribution of elevations and decreases was 8 and 9 eyes, which is equal to 47.1% and 52.9%. Two eyes dilated with Cyklopentolat-fenylefrin experienced a change in IOP post-dilation of ≥5 mmHg. Both were decreases. This is equal to 3.4%. This means that Tropikamid caused an elevation of ≥5 mmHg in 3.7% and a decrease in 4.2%. Cyklopentolat-fenylefrin did not cause any elevation of ≥5 mmHg, but a decrease in 3.4% (Figure 4).

In this study the eye with maximum decrease in IOP had a post-dilation IOP of 6 mmHg lower then baseline.

The eye with maximum increase in IOP post-dilation had a change of +9 mmHg. In 115 subjects, both eyes were included in the study. Twenty of these subjects experienced a post-dilation IOP change in which the right and left eye changed in different direction. This means that 17.4% of the subjects experienced an increased in one eye and a decreased in the other.

In many of the patients scheduled for a complete eyehealth-exam, additional parameters were collected and compared with each eye’s change in IOP post-dilation. In these correlation tests, 173 eyes were included and all were dilated with the single agent drug. The additional parameters were: refractive error (emmetropia, hyperopia, myopia), anterior chamber angle (estimated with van Herick’s method) and lens status (phakic, aphakic, pseudophakic). None of these parameters showed statistically significant association.

Figure 1. Change in IOP in single agent subjects.

Figure 2. Change in IOP in combination agent subjects.

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Figure 3. Percent with decrease in IOP >2 mmHg, no change (<2 mmHg), or increase in IOP >2 mmHg.

Figure 4. Percent with decrease in IOP ≥5 mmHg, no change (< 5 mmHg), or increase in IOP ≥5 mmHg.

DISCUSSION The purpose of this study was to investigate the change in IOP caused by a single agent drug, Tropikamid 0.5%, and a combination agent drug, Cyklopentolat-fenylefrin 0.75%+2.5%. The study also aimed to compare these drugs effect on the intraocular pressure to each other.

This study found that Tropikamid caused a change in IOP that was statistically significant. The mean change was a decrease in IOP of -0.29 ± 2.41 mmHg. Previous studies on this drug have shown no statistically significant effect on IOP, and post-dilation IOP has been equivalent to pre-dilation IOP (Pukrushpan et al., 2006; Oltulu et al., 2015). These results do not correspond with this study. It is interesting to discuss if the small mean decrease in IOP in this study could be considered equivalent to pre-dilation IOP, since a change this small might be clinically insignificant. Only one previous study, which investigated the effect of homatropine, another single agent anticholinergic drug, corresponds to this study’s mean change post-dilation (Christensen and Pearce, 1963).

Cyklopentolat-fenylefrin also caused a change in IOP

that was statistically significant, and the mean change was a decrease of -0.63 ± 1.99 mmHg. Since the effect on IOP of this combination agent has not previously been studied, the results can only be compared to studies using other combinations of an anticholinergic and an adrenergic agent. Tan et al. (2009) showed a post-dilation IOP significantly lower than pre-dilation IOP when using tropicamide 1% + phenylephrine 2.5% in subjects with diabetes mellitus. A decrease in IOP has also been shown in studies with normal subjects dilated with tropicamide 1% + phenylephrine 10%, with a mean change of -0.7 and -1.1 mmHg (Atalay et al., 2015a; 2015b). In another study on healthy individuals dilated with tropicamide 0.8% + phenylephrine 5%, the mean change in IOP was a decrease of -1.1 ± 2.5 mmHg right eye, and -0.7 ± 2.3 mmHg left eye (Qian et al., 2012). This mean decrease in IOP caused by combination agents, are consistent with the theory that drugs with greater impact on the ciliary tonus/accommodation increases the uveoscleral outflow and lowers the IOP (Christensen and Pearce, 1963; Harris, 1968; Toris et al., 1995; Alm and Nilsson, 2009).

The statistical analyses on the two drugs’ pre- and post-dilation IOP was done with different tests due to only one passing the normality test. It could have been wise to choose Wilcoxon matched-pairs signed-ranks test for both of the analyses since IOP is not normally considered sampled from Gaussian distributions.

Earlier studies have defined a change in IOP of >±2 mmHg as clinically significant (Pukrushpan et al., 2006; Qian et al., 2012; Atalay et al., 2015a; 2015b). Qian et al.

(2012) found a prevalence of IOP change >±2 mmHg in 35% of dilated subjects. There was an elevation in 11% of all subjects, and a decrease in 24.4% (Qian et al., 2012). This study showed a clinically significant change in 27.1% of those dilated with Tropikamid, and 28.8% of Cyklopentolat-fenylefrin subjects. An elevation of >2 mmHg occurred in 8.9% of Tropikamid subjects, and a decrease occurred in 18.2%. Cyklopentolat-fenylefrin caused an elevation >2 mmHg in 8.5% of all subjects and a decrease in 20.3%. These results are in line with previous studies where a combination of phenylephrine 10% + tropicamide 1% was used (Atalay et al., 2015a; 2015b).

The prevalence of elevations in IOP of ≥5 mmHg was 3.7% for eyes dilated with Tropikamid. No eye dilated with Cyklopentolat-fenylefrin showed an elevation of ≥5 mmHg. Both drugs caused decreases in IOP of ≥5 mmHg, the prevalence for eyes dilated with Tropikamid was 4.2%, and for Cyklopentolat-fenylefrin 3.4%. This corresponds to previous studies (Tan et al., 2009). In subjects with diabetes mellitus it has been found that 3.6% experience an increase in IOP post-dilation of ≥5 mmHg (Tan et al., 2009). The prevalence of IOP change of ≥5 mmHg was included in this study for many reasons.

A greater change in IOP post-dilation increases the risk of impact on the eye. It can therefor be of greater

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clinical value than a change in IOP of >2 mmHg. It is also a known fact that the diurnal variation of IOP is around 5 mmHg (Saude, 1993). This makes a measured change in IOP of 2 mmHg hard to trust.

In this study there was no statistically significant difference between the effect on IOP of the two drugs.

This suggests that the combination agent drug Cyklopentolat-fenylefrin 0.75%+2.5% can be used in clinical practise with an expected impact on IOP similar to that of Tropikamid 0.5%.

The cause of IOP change post-dilation is still uncertain.

It has been shown in previous studies that age, sex, ocular diagnosis, ocular medication, ethnicity, iris colour, pupil diameter, pre-dilation IOP, anterior chamber angle, lens status, and central corneal thickness does not clearly correlate with the IOP change post-dilation (Hancox et al., 2002; Qian et al., 2012; Atalay et al., 2015a; 2015b).

In this study additional parameters were compared with the change in IOP in 173 eyes. The additional parameters were refractive error, anterior chamber angle, and lens status. None of these parameters showed significant association to the change in IOP. This is consistent with earlier studies, and unfortunately makes it very hard to predict how an individual will respond to dilation. The only factor, which is known to increase prevalence of elevation in IOP post-dilation, is glaucoma (Christensen and Pearce, 1963; Harris, 1968; Hancox et al., 2002; Siam et al., 2007; Shihadeh et al., 2011). Previous studies have therefor suggested that since a significant elevation in IOP is of clinical importance, post-dilation IOP only needs to be measured on patients with glaucoma (Hancox et al., 2002; Pukrushpan et al., 2006; Tan et al., 2009). This study would suggest that since there is still no certain way to predict how the IOP will change after dilation, and some individuals without glaucoma do experience an unforeseen elevation, all patients should be re-measured after dilation.

This study also compared 115 individuals tendency to experience a similar change in IOP post-dilation in their two eyes. In most previous studies only one eye has been included, and it has been assumed that the change of pressure in one eye strongly predicts the change in the other. In this study 17.4% of the subjects experienced an elevation in one eye and a decrease in the other. Hancox et al. (2002) found a strong association between the change in IOP of the right and left eye. There seems to be no obvious reason to why these results are not corresponding with this study. The association between the eyes response in IOP post-dilation is of great clinical interest and value, and is urged to be studied further.

The greatest change in post-dilation IOP in this study was an elevation of +9 mmHg and decrease of -6 mmHg. Both of these were found in subjects dilated with Tropikamid. All subjects that showed an elevation post-

dilation were kept in the clinic and re-measured every 5-10 minutes until IOP started to decline. No elevation required medical intervention. The greatest elevation (+9 mmHg) was found in a 84 year old woman. She had no previous history or indications that could have helped predict this elevation. The pre-dilation IOP was 21 mmHg in both eyes, and 30 minutes post-dilation it was measured to 28 mmHg in the right eye and 24 mmHg in the left. Fifty minutes post-dilation it was 30 mmHg in the right eye and 26 mmHg in the left. The woman lived very near the clinic and was allowed to go home for a few hours with clear instructions to return immediately if she felt any change in her state of health or experienced any symptoms in the eyes or vision. She returned 3.5 h post-dilation feeling fine and IOP had then returned to pre-dilation levels.

Measuring of IOP has in most studies been done with Goldmann applanation tonometry (Harris, 1968; Hancox et al., 2002; Pukrushpan et al., 2006; Siam et al., 2007; Shihadeh et al., 2011; Qian et al., 2012; Kim et al., 2012; Atalay et al., 2015a; 2015b). In this study, for practical reasons, IOP was measured with Reichert Ocular Response Analyzer (ORA), since it is a fast, non-invasive method that also considers the biomechanical properties of the cornea. Goldmann applanation tonometry (GAT) is considered gold standard for IOP measuring, but studies comparing and evaluating different measurement techniques has shown that GAT and ORA can be used interchangeably (Lanza et al., 2016).

There were some limitations in this study. The subjects were patients from both the regular clinic, and an ophthalmologist and retinal surgeon. The first group received a complete eye-health-exam, and the second group received a much smaller optometry-exam prior to their meeting with the ophthalmologist. The study chose to include both groups for the single purpose of studying as many eyes as possible. With this choice came three limitations. The time between dilation and post-dilation measuring of IOP varied quite a lot, since the ophthalmologist’s patients mostly had a much shorter visit at the clinic. The second limitation was that the patients in the second group all had some kind of retinal problem, which could have affected their response to dilation. Thirdly the two drugs were not given to the same number of eyes, which can have affected the statistic results. For future studies on these two drugs, it would be interesting to compare their effect on IOP in the same subject. It is possible that this study found no significant difference between the drugs’ effect on IOP because they were not compared in the same individual. The time between dilation and post-dilation IOP measuring should, in a second study be the same for all subjects.

Since there are so many unanswered questions in the field of intraocular pressure, further studies are needed

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to widen our knowledge and improve everyday clinical practice.

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Redaktörens kommentar:

Introduktion och metoddelen bör läsas för att kunna ta del av resultatet som är intressant. Diskussionsdelen är spännande att läsa, med tankar om resultatet.

Biometrisk utvärdering av förändringar i främre kammaren efter fysiologisk pupilldilatation utförda med Pentacam och optisk koherens tomografi (OCT) Författare: Florent Aptel, Christophe Chiquet, Sylvain Beccat, Philippe Denis Sammanfattning av Catarina Ericson

Här utvärderades förändringar i främre kammaren (AC) morfologi och iris volym inducerad av fysiologisk mydriasis hos patienter med akut trångvinkel och ålders-, köns- och central AC-djup matchades med misstänkta primära trångvinklar (PACS) samt 40 ålders- och könsmatchade ögon med normal öppenvinkel. De avbildades med en Pentacam och optisk koherens tomografi (ASOCT) på främre segmentet under ljusförhållanden, och efter 5 minuter av mörker åter med hjälp av AS-OCT. Central AC djup, hornhinnans krökning, axiell längd, och lins tjocklek skilde sig inte signifikant mellan PACS och andra ögon. När man går från ljust till mörkt minskade kammarvinkeln signifikant mer i andra ögon än i PACS (68 % vs 52 %, p <0,001). När man går från ljust till mörkt, ökade den genomsnittliga iris volymen i andra ögon (från 45,34 6 2,1 till 47,68 6 3,2 mm3, P <0,01), medan den minskade i de flesta PACS ögon (från 45,01 6 2,2 till 42,11 6 2,3 mm3, P <0,01), och i alla öppenvinkel ögon (från 44,68 6 1,16-41,67 6 1,20 mm3, P <0,01).

Glaucoma

Biometric Evaluation of Anterior Chamber Changes after Physiologic Pupil Dilation Using Pentacam and Anterior Segment Optical Coherence Tomography 3 1,2 Denis4 Florent Aptel,1,2 Christophe Chiquet, Sylvain Beccat, and Philippe

PURPOSE. We evaluated changes in anterior chamber (AC) morphology and iris volume induced by physiological mydriasis in fellow eyes of acute angle-closure patients, and age-, sex-, and central AC depth-matched primary angle-closure suspects (PACS).

METHODS. In our study, 21 fellow eyes of patients with acute angle closure; 40 age-, sex-, and central AC depth-matched PACS eyes; and 40 age- and sex-matched normal open-angle eyes were imaged using a Pentacam and anterior segment optical coherence tomography (AS-OCT) under light conditions, and after 5 minutes of darkness using AS-OCT. Iris volume was estimated using AS-OCT and a customized imageprocessing software.

RESULTS. Central AC depth, corneal curvature, axial length, and lens thickness did not differ significantly between the PACS and fellow eyes. When going from light to dark, angle opening distance at 500 lm decreased significantly more in fellow eyes than in PACS (�68% vs. �52%, P < 0.001). When going from in the light to dark, the mean iris volume increased significantly 3 fellow eyes (from 45.34 6 2.1 to 47.68 6 3.2 mm , P < 0.01), whereas it decreased significantly in most PACS eyes (from 3 45.01 6 2.2 to 42.11 6 2.3 mm , P < 0.01), and in all3 openangle eyes (from 44.68 6 1.16 to 41.67 6 1.20 mm , P < 0.01). Based on multivariate analysis, significant predictors of angle narrowing under darkness (relative change in angleopening distance 500) were fellow eyes compared to PACS (b ¼ �2.98, SE ¼ 0.249, P ¼ 0.005) and higher iris volume increase with pupil dilation (b ¼ �3.146, SE ¼ 0.432, P ¼ 0.015).

CONCLUSIONS. Under dark conditions, angles of fellow eyes closed dramatically more than did those of PACS. Iris volume increase per millimeter of pupil dilation is an independent predictor of angle narrowing in darkness. (Invest Ophthalmol Vis Sci. 2012;53:4005–4010) DOI:10.1167/iovs.11-9387 ver the past decade, new anterior chamber (AC) imaging techniques, such as ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT), have provided numerous valuable insights into the pathogenesis of angle-closure glaucoma, and demonstrated that the well-identified anatomic

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2 From 1UJF-Grenoble 1, Grenoble, France; the Department of Ophthalmology, University Hospital, CHU Grenoble, Grenoble, France; the 3 Department of Ophthalmology, Edouard Herriot 4 Department of Ophthalmology, Hospital, Lyon, France; and the Croix-Rousse Hospital, Lyon, France.

Submitted for publication December 22, 2011; revised May 4, 2012; accepted May 13, 2012.

Disclosure: F. Aptel, None; C. Chiquet, None; S. Beccat, None;

P. Denis, None Corresponding author: Florent Aptel, Clinique Universitaire d’Ophtalmologie , Centre Hospitalo-univer sitaire de Grenoble, BP217, 38043 Grenoble cedex 09, France; faptel@chu-grenoble.fr.

1 risk factors are not sufficient to produce angle closure.

Clearly, anatomic conditions, such as shallow AC, shorter axial vault, lens greater or length, larger lens thickness and volume, closure, are statistically demonstrated risk factors of angle 2–7 However, angle-closure glaucoma, or acute angle closure. the anatomic mechanisms taken alone do not explain that characteristics 80%–90% of the eyes with such predisposing never have angle closure, that Asians have a much higher prevalence of angle closure and angle-closure glaucoma than Caucasians despite often comparable biometric characteristics, and that the numerous available biometric measurements have a poor predictive power to identify eyes a priori that will have 7–12 further development of angle closure and need iridotomy.

Recent studies have investigated the role of the dynamic response of some intraocular structures to physiologic conditions, particularly the response of the iris to pupil dilation, and have suggested that angle closure could be due to abnormal dynamic behavior of the iris occurring in anatomically predisposed eyes. First, Quigley et al., using anterior segment OCT (AS-OCT), found that the iris crosssectional area is nearly two times smaller after physiologic or pharmacologic pupil dilation in healthy eyes, and that a lower reduction of the iris cross-sectional area after pupil 13dilation may be a potential risk factor for angle closure. They hypothesized that the normal iris loses volume in the dark or after pharmacologic pupil dilation, and that eyes with angle closure lose less iris volume on dilation, contributing to iridotrabecular apposition. In addition, we demonstrated previously, using customized software allowing us to estimate the whole iris volume from AS-OCT data, that iris volume increases after pupil dilation in narrow-angle eyes predisposed to acute angle closure, whereas it decreases in healthy open-angle eyes.14 We suggested that these changes could result from a change in vascular tonus leading to venous outflow decrease and intravascular volume increase. We compared the fellow eyes of patients with acute angle closure with healthy openangle eyes. By extrapolation, we and others have hypothesized that the behavior of the iris may explain that a small proportion of narrow-angle eyes develop angle closure, whereas the biometric majority of narrow-angle eyes with comparable 14–16 characteristics do not develop angle closure.

The objective of our present study was to evaluate the changes in AC morphology after physiologic mydriasis in the fellow eyes of acute angle-closure patients compared to primary angle-closure suspects (PACS; i.e., asymptomatic narrow-angle eyes) and normal open-angle eyes. To evaluate the role of the dynamic response of the iris more precisely (i.e., risk factors not related to the static anatomy), we compared age-, sex-, and AC depth-matched PACS eyes. We assessed prospectively the anterior segment static anatomy using a Pentacam (Oculus, Wetzlar, Germany) and evaluated change in iris volume using AS-OCT.

No. 7 Investigative Ophthalmology & Visual Science, June 2012, Vol. 53, Inc. Copyright 2012 The Association for Research in Vision and Ophthalmology,

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