text:
12 Intracameral Mydriatics in Cataract Surgery Anders Behndig, Björn Lundberg and Gunnie Bäckström Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden 1. Introduction The routines for cataract surgery have undergone a remarkable development over the past two to three decades (Lundstrom, Stenevi et al. 2002). Surgical techniques have improved constantly, and now require less extensive anesthesia (Behndig and Linden 1998), decreased need for hospitalization (Oshika, Amano et al. 2001; Yi, Flanagan et al. 2001) and fewer postoperative controls (Edwards, Rehman et al. 1997). Still, it is remarkable that some perioperative routines have undergone very little change, despite the general improvement. One of those more or less unchanged routines have been the routine for preoperative pupil dilatation. In a phacoemulsification cataract procedure, a large proportion of the work is done within the eye, and sufficient mydriasis is a prerequisite to allow for visualization of the capsulorhexis and the lens. Conversely, poor mydriasis during cataract surgery increases the risk of intraoperative complications such as posterior capsule rupture (Artzen, Lundstrom et al. 2009), A small pupil can make instrument maneuvering within the eye more difficult, make the capsulorhexis hydrodissection and phacoemulsification more difficult to perform of the lens nucleus can lead to an increased risk of iris damage, and increases the risk also for other complications, including sphincter tear, bleeding and dropped nucleus. Iris damage due to a small pupil can result in an irregular and atonic pupil with photophobia and other types of discomfort. Traditionally, topical administration of a combination of anticholinergic (passive) mydriatic agents such as cyclopentolate 1%, tropicamide 1%, homatropine 5% or scopolamine 0.25% and sympathomimetic (active) mydriatic agents such as phenylephrine 2.5% to 10% has been the preferred way to achieve mydriasis. Often, topical nonsteroidal antiinflammatory drops such as indomethacin 1%, flurbiprofen 0.03%, or suprofen 1% are also added, to enhance and prolong the mydriatic effect. The administration of the eye drops is typically started 45 minutes to 1 hour before the surgical procedure. It is clear that this regimen has some disadvantages. First, it is well known that the slow penetration of mydriatic substances through the cornea renders a slow pupil enlargement (Lovasik 1986; Chien and Schoenwald 1990) with a maximum mydriatic effect at 30 minutes for cyclopentolate (Haaga, Kaila et al. 1998) and as much as 75 minutes for phenylephrine. (Matsumoto, Tsuru et al. 1982) In practice, this means that the waiting time for the pupil to dilate often is several-fold longer than the surgical procedure itself. Second, limited bioavailability of topically administered substances means a significant systemic absorption (Doane, Jensen et al. 1978; Kaila, Huupponen et al. 1989; Haaga, Kaila et al. 1998) which in turn may increase the risk 150 Cataract Surgery for cardiovascular side-effects, (Fraunfelder and Scafidi 1978; Fraunfelder and Meyer 1985) especially in high-risk groups such as persons with hypertension, (Hakim, Orton et al. 1990) or cardiovascular diseases, (Meyer and Fraunfelder 1980) and in children. (Ogut, Bozkurt et al. 1996; Elibol, Alcelik et al. 1997), Third, even if a good mydriasis is achieved initially, the mydriatic effect often tends to diminish during the operation, and especially when the procedure takes longer than expected. Different solutions have been suggested to prolong the mydriatic effect from topical mydriatics such as preoperative treatment with diclofenac (Antcliff and Trew 1997), viscous 10% phenylephrine, (Duffin, Pettit et al. 1983) or intraoperative intracameral epinephrine. (Duffin, Pettit et al. 1983; Liou and Yang 1998). In 2003, we first introduced the concept of intracamerally injected mydriatics, in which mydriatic substances were mixed with the intracameral lidocaine given at the start of the phacoemulsification cataract procedure. As we will see below, a local anesthetic will also have an additive, passive mydriatic effect when injected intracamerally (Cionni, Barros et al. 2003). We early found that when using a regimen involving intracameral mydriatics, some of the disadvantages with topical mydriatics are avoided, since the method means no preoperative waiting time and also reduced doses of the mydriatic substances - and thereby likely lowers the risk for systemic side-effects (Lundberg and Behndig 2003) (Morgado, Barros et al. 2010). In our own current setting, a preservative-free mixture of phenylephrine 1.5% and lidocaine 1% is used, but other solutions have been proposed and used clinically, mainly preservative-free epinephrine 0.025% with lidocaine 0.75%, or lidocaine 1% only. Other substances have been tried experimentally and proven efficient, such as epinine 0.3% - 3.0% and isoprenaline 0.3%. An interesting consequence of the concept of intracameral mydriatics in intraocular surgery is also that is provides us with a possibility to use other mydriatic substances than the traditional anticholinergics and -adrenergics (Cionni, Barros et al. 2003; Lundberg and Behndig 2009; Myers and Shugar 2009), since the doses of potentially cardiotoxic drugs can be reduced, and we no longer have to consider limitations in bioavailability because of the corneal barrier. Cyclopentolate, whether given topically or intracamerally, has been demonstrated not to contribute to increased mydriasis when using intracameral mydriatics (Lundberg and Behndig 2008), and neither has epinephrine added to the intraoperative infusion (Lundberg and Behndig 2007). Cyclopentolate and similar substances are therefore often abandoned in intracameral mydriatics regimens today, and accordingly, intraoperative epinephrine infusion is more seldom used today by surgeons using intracameral mydriatics. With intracameral mydriatics, the mydriasis generally reaches 95% its final value within 20-30 seconds. Intracameral mydriatics render slightly smaller pupils than topical mydriatics at a maximum dosage, but with intracameral mydriatics, the pupils do not contract intraoperatively, as with topical mydriatics. As insufficient adrenergic stimulation of the pupil dilator appears to be a major factor causing intraoperative pupil contraction during phacoemulsification cataract surgery (Antcliff and Trew 1997; Liou and Yang 1998; Backstrom and Behndig 2006), intracameral mydriatics containing an adrenergic substance is effective in re-dilating the pupil (Backstrom and Behndig 2006; Mori, Miyai et al. 2010), and are also used to prevent intraoperative floppy iris syndrome (IFIS) (Gurbaxani and Packard 2007; Takmaz and Can 2007; Cantrell, Bream- Rouwenhorst et al. 2008). With intracameral mydriatics, the patients perceive less initial glare from the operation microscope light, as the pupil is small at the beginning of the procedure. The intracameral mydriatics concept has been extensively studied from a safety perspective by us and others, and is found to be safe with no increase in corneal endothelial Intracameral Mydriatics in Cataract Surgery 151 cell loss (Lundberg and Behndig 2003) (including at long-term follow-up), inflammatory reaction, postoperative corneal swelling (Lundberg and Behndig 2003) or macular edema (Johansson, Lundberg et al. 2007). Furthermore, in routine surgery, the surgical performance does not differ from when a standard topical mydriatic regimen is used (Behndig and Eriksson 2004). Intracameral mydriatics comprise a rapid, effective and safe alternative to topical mydriatics in phacoemulsification surgery. It has a potential to simplify the preoperative routines, and for certain high-risk groups, it may reduce the risk for cardiovascular side effects. 2. Intracameral mydriatics 2.1 Published studies Several studies have been published suggesting different routines for the use of intracameral mydriatics, and evaluating the various regimens. This chapter aims to give a brief overview of the published studies. 2.1.1 Initial studies: Cyclopentolate/phenylephrine/lidocaine In 2003 our group published a prospective, randomized, double-masked study (Lundberg and Behndig 2003) in which the patients were randomly assigned either of two treatments: traditional topical mydriatics with 3 drops each of cyclopentolate 1% and phenylephrine 10% with 15 minutes interval plus 150µl of preservative-free xylocaine 1% intracamerally at the beginning of the procedure, or intracameral mydriatics with placebo eye drops and 150 µl of a preservative-free mixture of cyclopentolate .1%, phenylephrine 1.5% and lidocaine 1% intracamerally. In this study, the intracameral injection was given by the other surgeon, and thus, neither the operating surgeon nor the patients were aware of which of the two treatments was given, allowing for the double-masked design. The pupil sizes were recorded during surgery using video recordings, and also at one day and one month postoperatively, using the Orbscan II®, (Marsich and Bullimore 2000) (Bausch & Lomb Surgical, Inc., San Dimas, CA). In addition, corneal endothelial morphometry, ETDRS visual acuity (Camparini, Cassinari et al. 2001) intraocular pressure (IOP) and intraoperative blood pressure and pulse were measured. After injection of intracameral mydriatics, the pupils reached 95±3% of their maximum size after 20 seconds (Figure 1). In the intracameral mydriatics group, the pupil size after viscoelastic injection was 6.7±1.0 mm, which was about 1 mm smaller than with topical mydriatics, but when using intracameral mydriatics the pupils continued to enlarge throughout the procedure as opposed to when topical mydriatics were used. The corneal endothelial morphometry did not differ between intracameral and topical mydriatics. A significant pulse deceleration was seen with topical, but not with intracameral mydriatics. This likely resulted from the fact that the total dose of phenylephrine with intracameral mydriatics in this setting was only 23% of that with topical mydriatics. The results of this study were confirmed in a small pilot series of 10 patients published by Soong et al in 2006 (Soong, Soultanidis et al. 2006), where it was also concluded that the intracameral technique is a safe, rapid, and effective alternative to conventional topical mydriasis in phacoemulsification cataract surgery, and that it can reduce the duration of stay within the outpatient surgical units. The latter is not least important considering the high turnover of modern cataract surgery. The authors had also, at the time of publication, continued with another 280 uneventful routine cases using the same technique. 152 Cataract Surgery 100 90 80 70 60 50 40 30 20 10 0 0 5 10 15 20 Time after injection, s. Fig. 1. Pupil size after injection of intracameral mydriatics. Pupils reached 95±3% of their maximum size after 20 seconds. 2.1.2 Initial studies: Lidocaine At the same time as the above mentioned study (in fact in the same number of Journal of Cataract and Refractive Surgery) Robert J Cionni et al published an article describing the use of 300 to 500µl of Xylocaine-MPF 1% injected intracamerally as the sole mydriatic agent (Cionni, Barros et al. 2003). Epinephrine 0.3 cc of 1:1000 was also added to the infusion. The authors state that "Mydriasis begins immediately, enabling the surgeon to proceed within 90 seconds." In this study, the first 12 patients had adequate mydriasis, with a mean pupil size before dilation of 2.4 mm (range 1.5 to 3.1 mm) and after intracameral Xylocaine-MPF 1%, 6.5 mm (range 5.2 to 7.2 mm). 2.1.3 Further studies on lidocaine The results from Cionni's study were confirmed in 2007 by Nikeghbali et al (Nikeghbali, Falavarjani et al. 2007) in a prospective comparative case series including 57 patients randomized to receive either topical mydriatics (30 eyes) or intracameral lidocaine (27 eyes) to dilate the pupil. The topical mydriatics given consisted of 3 drops of cyclopentolate 1% Intracameral Mydriatics in Cataract Surgery 153 and phenylephrine 5% given 5 minutes apart starting 60 minutes before surgery. The intracameral group received 0.2-0.3 ml of preservative-free lidocaine 1% intracamerally. Noteably, in this study, no epinephrine was added to the irrigating solution. The mean pupil dilation was 4.52±0.08mm in the intracameral group and 4.06±0.09 mm in the topical group, and no difference in the overall subjective surgical performance was noted. Similar results were also published the following year in the Indian Journal of Ophthalmology by the same group; in a case series of 31 consecutive cases the pupils dilated from 2.63±0.33 mm to 7.03±0.61 90 seconds after injection of 0.2 to 0.3 ml of preservative-free lidocaine 1%, and no negative effects on the surgical performance were noted (Nikeghbali, Falavarjani et al. 2008). Jayadev and Nayak also published a short report on this regimen in 2007 (Jayadev and Nayak 2007). Noticeably, both the studies by Nikeghbali (Nikeghbali, Falavarjani et al. 2007; Nikeghbali, Falavarjani et al. 2008) and Jayadev (Jayadev and Nayak 2007) demonstrate significantly larger pupils after intracameral lidocaine without preoperative topical mydriatics, than we have seen in our investigations (Lundberg and Behndig 2008). This difference in effect from intracameral lidocaine may be due to population differences, differences in lidocaine dosage, or the fact that the pupil size was measured 90 seconds after the intracameral lidocaine injection in the studies in question. Generally, the onset of mydriasis from a passive dilator such as lidocaine, administered intracamerally will be a bit slower than from the combination of an active and a passive dilator. 2.1.4 Surgical performance In 2004, a series of 198 consecutive cases operated with intracameral mydriatics was compared to the previous 198 cases operated with traditional topical mydriatics (Behndig and Eriksson 2004). Several pre- intra- and postoperative parameters were registered, the subjective surgical performance was graded after each procedure, and the change in pulse and oxygen saturation induced by the ICM injection was registered. Despite the smaller pupils at the initiation of the procedures, no increase in operation time or complication rates was seen with with intracameral mydriatics, compared to when standard topical mydriatics were used. Furthermore, the subjective surgical performance was ranked as equally good for both groups. The studies from Nikeghbali et al (Nikeghbali, Falavarjani et al. 2008) confirmed the results of a surgical performance similar to when using topical mydriatics. 2.1.5 Handling intraoperative pupil constriction In 2006, a prospective, randomized, placebo-controlled, double-masked study study involving 80 patients was published, aiming to determine whether intracameral mydriatics can redilate pupils that contract during phacoemulsification cataract surgery (Backstrom and Behndig 2006). Patients were randomized to receive or not receive an addition of 0.6 µg/ml of epinephrine to the irrigation solution, and further randomized to have an injection of our original intracameral mydriatics mixture or placebo after the phacoemulsification and cortex cleaning. The pupil sizes were registered at different time points during surgery and the day after surgery. There was a greater degree of pupil contraction in the absence of epinephrine in the irrigation solution compared to in the presence of epinephrine. In cases where no epinephrine was added to the irrigation solution, the intracameral mydriatics solution given significantly redilated the pupils at 30 seconds (p<0.001 compared with placebo) as well as at 2 mins (p = 0.015 compared with placebo). These findings are also well 154 Cataract Surgery in accordance with the later findings of Mori et al, demonstrating a satisfactory pupil ditatation with an intracameral solution containing phenylephrine and tropicamide in cases with insufficient pupil dilatation from topical mydriatics (Mori, Miyai et al. 2010). The findings of the 2006 study also confirms earlier reports that insufficient adrenergic stimulation of the pupil dilator is a major factor causing intraoperative pupil contraction during phacoemulsification cataract surgery (Antcliff and Trew 1997; Liou and Yang 1998). Likely, this factor also contributes to the absence of pupil contraction seen when using a large bolus dose of an adrenergic substance at the beginning of a surgical procedure (as with intracameral mydriatics), as opposed to when topical mydriatics are employed (Lundberg and Behndig 2003; Lundberg and Behndig 2007). 2.1.6 Omitting epinephrine infusion It has long been known that addition of epinephrine to the irrigating solution prevents intraoperative pupil constriction in phacoemulsification surgery with topical mydriatics (Antcliff and Trew 1997; Liou and Yang 1998; Backstrom and Behndig 2006). To investigate whether this holds true also with intracameral mydriatics, we performed a study in 2007 to evaluate the possibility of removing epinephrine from the irrigating solution in phacoemulsification surgery when using intracameral mydriatics (Lundberg and Behndig 2007). In this prospective, randomized, double-masked study involving a total of 140 cataract patients, the first part of the study included 90 patients divided into two groups. Patients in both groups were given 150 µl of the intracameral mydriatic solution at the beginning of the procedure. In the first group, 0.6 µg/ml epinephrine was added to the irrigating solution; no epinephrine was added to the irrigation solution used in the second group. The second part of the study involved 50 patients, all of whom were given topical mydriatics and then similarly divided into two groups and treated as in the first part of the study. As noted in our initial studies (Lundberg and Behndig 2003), the pupil sizes generally increased during the procedures with intracameral mydriatics. Interestingly, this increase was significantly greater without epinephrine (13 +/- 19% versus 4 +/- 14%; p = 0.02). In the topical mydriatics setting, pupil sizes decreased intraoperatively in both groups; significantly more without epinephrine (- 5 +/- 4% versus - 12 +/- 7%; p < 0.001). We concluded that an irrigating solution without epinephrine can safely be used with intracameral mydriatics. The increase in pupil size during the procedure was even shown to be greater without epinephrine. As epinephrine is unstable in a solution with physiological pH, time-consuming repeated blending procedures are needed, which can be avoided if intracameral mydriatics are used. The study also confirms earlier findings that epinephrine is beneficial when using topical mydriatics (Antcliff and Trew 1997; Liou and Yang 1998; Backstrom and Behndig 2006). 2.1.7 Omitting cyclopentolate Since we suspected that the onset of mydriasis from intracameral cyclopentolate was too slow for the substance to be meaningful as an intracameral mydriatic, and that the passive dilating effect of lidocaine would be quite sufficient together with an adrenergic substance such as phenylephrine, we decided to assess the separate mydriatic effects of intracameral cyclopentolate hydrochloride, lidocaine hydrochloride and phenylephrine hydrochloride in another prospective randomized double-masked study published in 2008 (Lundberg and Behndig 2008). The study involved a total of 56 cataract patients: in 16 patients, lidocaine 1%, phenylephrine 1.5%, and cyclopentolate 0.1% were injected sequentially one after the other. Intracameral Mydriatics in Cataract Surgery 155 Phenylephrine and cyclopentolate were randomized to switch in order, creating 2 study groups with 8 patients in each. In part two of the study, an additional 40 patients were randomized to receive either all three substances intracamerally (lidocaine 1%, phenylephrine 1.5%, and cyclopentolate 0.1%) or intracameral lidocaine 1% and phenylephrine 1.5% only. Lidocaine alone gave a significant pupil dilation to 4.9±0.6 mm. When cyclopentolate was injected next, the pupil size increased further by 1.3±0.6 mm. When phenylephrine was added, the pupil increased an additional 0.7±0.4 mm. In the second group, in which phenylephrine was given directly after lidocaine, the pupil size increased by 2.1±0.5 mm. When cyclopentolate was added as the third substance, no significant change in the pupil size could be seen (Figure 2). Accordingly, no statistically significant differences in pupil size were observed between the 20+20 patients who were given intracameral mydriatics with or without cyclopentolate. Noteably, though, the day after surgery, the pupils were significantly larger in the cyclopentolate group (4.7±1.1mm) than in the group without cyclopentolate 2.9±0.8 mm. We concluded that cyclopentolate administrated intracamerally has no immediate additive mydriatic effect to intracameral lidocaine plus phenylephrine, or to put it more precisely, intracameral cyclopentolate dilates the pupil after surgery, but not during surgery. After this study, cyclopentolate was omitted from our clinical routine preparation. Fig. 2. The figure shows the pupil sizes (in mm, Y-axis) at different time points (in seconds, X-axis) after stepwise intracameral injections of lidocaine 1% (given first in both gruops, left part of the diagram), phenylephrine 1.5% and cyclopentolate 0.1%, 150 mL each. The order of the latter 2 injections was randomized (black circles: phenylephrine first; n=7; white circles: cyclopentolate first; n=8). Note that the addition of phenylephrine has a pronounced mydriatic effect, as opposed to cyclopentolate. Cyclopentolate given after phenylephrine has no detectable additive mydriatic effect. 156 Cataract Surgery A later study showed that when 2 drops of topical phenylephrine 10% combined with 150µl of intracameral lidocaine 1% is given at the beginning of a phacoemulsification procedure, no additive mydriatic effect can be seen from administrating preoperative topical cyclopentolate (Lundberg and Behndig 2009). The study was designed as a prospective, double-masked, randomized trial including 20 patients with age-related cataract. Initially, the pupil sizes were significantly smaller in the group where no topical cyclopentolate had been given - 4.8±1.2 mm compared to 6.5±1.4 mm, but the lidocaine injection increased the pupil sizes significantly in the absence of cyclopentolate, so that the pupil sizes were equalized throughout the surgical procedure for the both treatments. These findings show that the passive diating effect from intracameral lidocaine is sufficient, without topical passoive diating agents, and that preoperative topical cyclopentolate can be omitted when intracameral lidocaine is used. Fig. 3. The figure demonstrates the pupil sizes (in mm, Y-axis) at different time points during the phacoemulsification process (X-axis) before and after the intracameral injection of 150µl lidocaine 1% Both treatment groups were given 2 drops of topical phenylephrine 10%; group 2 (grey bars) were also given 2 drops of topical cyclopentoloate 1%. Note that intracameral lidocaine has a pronounced mydriatic effect, noticeable when preoperative cyclopentolate is not given, and that both groups have practically identical pupil sizes throughout the procedure from after the injection of the ophthalmic viscosurgical device (OVD) and on. Intracameral Mydriatics in Cataract Surgery 157 2.1.8 Epinephrine/lidocaine In their paper "Optimizing the intracameral dilation regimen for cataract surgery: prospective randomized comparison of 2 solutions" from 2009, William G Myers and Joel K Shugar compared the efficacy of a solution of epinephrine 0.025% and lidocaine 0.75% in fortified balanced salt solution ("epi-Shugarcaine") and the original solution from our group (cyclopentolate 0.1%, phenylephrine 1.5%, and lidocaine 1%). The study was designed as a pair-eye single-masked prospective study involving 84 eyes of 42 patients. Topical tropicamide was given to both treatment groups. The pupils were statistically significantly larger with epi-Shugarcaine; 0.528 mm larger 1 minute after instillation and 0.34 mm larger at the end of the procedure (Myers and Shugar 2009). Since epinephrine is a much more unspecific adrenergic stimulator than the specific -receptor phenylephrine, the findings of this important study indirectly indicate that adrenergic receptors other than the -receptor stimulated by phenylephrine may be involved in the mydriatic response from intracamerally administered mydriatics. Subsequent studies have lent further support to this theory, as we will see below. 2.1.9 Tropicamide/phenylephrine In a study from 2010, Mori et al investigated the efficacy and safety of intracameral injection of a commercially available eye drop containing 0.5% tropicamide and 0.5% phenylephrine hydrochloride (Mori, Miyai et al. 2010), demonstrating no increased damage to cultured human corneal endothelial cells, and a good mydriatic effect in cases with poor mydriasis after preoperative topical mydriatics. 2.1.10 Cardiovascular safety Cardiovascular effects from topical mydriatic substances have been reported by many authors thoughout the years (Fraunfelder and Scafidi 1978; Meyer and Fraunfelder 1980; Fraunfelder and Meyer 1985; Hempel, Senn et al. 1999; Motta, Coblentz et al. 2009). A rapid absorption of anticholinergic and/or adrenergic substances via the nasal mucosa can render surprisingly high systemic levels of the substance. In our first two studies, we could se no signs of negative cardiovascular effects from intracameral myriatics (Lundberg and Behndig 2003; Behndig and Eriksson 2004), which is well in accordance with the facts that the doses of the adrenergic and anticholinergic substances are lower when the substance is administered intracamerally, and that there is likely to be a smaller proportion of the drug that enters the lacrimal drainage system with intracameral administration. Morgado et al confirmed in a study from 2010 involving 90 patients that topical mydriatics is more efficient from an initial mydriatic point of view, but intracameral mydriatics are safer from a cardiovascular point of view (Morgado, Barros et al. 2010). Taken together, the reports on cardiovascular safety combined with the widespread clinical routine use of intracameral mydriatics are reassuring – the risk of systemic side effects is not likely to be higher with the intracameral route of administration. 2.1.11 Macular safety Many investigators have reported an association between the use of epinephrine and macular edema in glaucoma patients (Kolker and Becker 1968; Thomas, Gragoudas et al. 1978; Classe 1980; Mehelas, Kollarits et al. 1982), particularly in aphakia, but also in pseudophakia, a condition known as epinephrine maculopathy (Miyake, Shirasawa et al. 158 Cataract Surgery 1989). It has been hypothesized that epinephrine maculopathy is induced by a mechanism involving prostaglandins or other eicosanoids and not directly by epinephrine (Miyake, Shirasawa et al. 1989). Whatever the exact mechanisms behind epinephrine maculopathy may be, it is particularly important to rule out negative effects on the macula from the rather large doses on adrenergics given in intracameral mydriatics. Therefore, in 2007, an investigation aiming to quantify the macular edema induced by intracameral phenylephrine and lidocaine in phacoemulsification surgery was undertaken (Johansson, Lundberg et al. 2007). Optical coherence tomography (OCT) has been used in several studies to assess the macular thickness after cataract surgery (Sourdille and Santiago 1999; Biro, Balla et al. 2006; Ching, Wong et al. 2006), including randomized trials to evaluate intraoperative treatments (Ball and Barrett 2006). With this highly sensitive instrument, minute postoperative macular thickness increases can be detected in a high proportion of cataract patients, also after uneventful surgery (Sourdille and Santiago 1999; Biro, Balla et al. 2006). Such changes, although subtle, can have a clinical relevance, being associated with decreased contrast sensitivity (Ball and Barrett 2006) or visual acuity (Sourdille and Santiago 1999). In a randomized study of 22 patients, 11 patients were given 150 µl of a mixture of phenylephrine 1.5% and lidocaine 1% intracamerally for mydriasis and anesthesia. The control group (n = 11) was given conventional topical mydriatics and intracameral lidocaine. No differences in macular edema between the 2 treatments could be noted on optical coherence tomography. The degree of foveal thickness increase found in the study, with a thickness increase exceeding 15µm in about 20% of the cases, is in the same range as previously reports from other reports with topical mydriatics (Sourdille and Santiago 1999; Ball and Barrett 2006). Similar results have later been reported also for intracameral epinephrine from Bozkurt et al. In a consecutive, randiomized case series of a total of 158 uneventful cataract procedures half of the eyes were given 0.2 ml of 0.02% epinephrine as an intracameral injection. No difference was seen in central macular thickness with optical coherence tomography at any time point up to 6 months after surgery. In both treatment groups, the increase in macular thickness from preoperatively to 1, 3, and 6 months postoperatively was significant. In this rather large series, clinically significant macular edema was noted in 3 eyes in the epinephrine group and 3 eyes in the control group. The authors concluded that intracameral injection of 0.2 ml of 0.02% epinephrine did not increase the risk for macular edema after uneventful phacoemulsification. 2.1.12 Long term follow-up The results from 40 of the cases from the original 2003 study on intracameral mydriatics were evaluated after 6 years, to assess if any long term complications such as posterior capsule opacification would be more frequent in patients operated with intracameral mydriatics. In the study, the visual acuity was measured using the ETDRS-fast protocol (Klein, Klein et al. 1983; Camparini, Cassinari et al. 2001), and the intraocular pressure, the grade of inflammation inflammation, the corneal thickness and the corneal endothelial cell loss were evaluated. The degree of posterior capsule opacification was assessed from standardized photographs using a digital camera. The grading of the posterior capsule opacifiaction (fraction and severity) was done with the POCOman program (Accessed from James Boyce, PhD (Bender, Spalton et al. 2004; Ronbeck, Zetterstrom et al. 2009)). The same masked observer performed the measurements twice for every image and the mean of the 2 measurements was calculated. Intracameral Mydriatics in Cataract Surgery 159 At 6 years, no statistically significant differences could be observed in visual acuity, intraoucular pressure and pupil size. The corneal thickness and endothelial cell loss did not differ significantly between the two treatment groups. At the 6 year follow up the total endothelial cell loss was 16.5 ± 14.6% in the TM group vs. 15.0 ± 15.4 % in the intracameral mydriatics group (P=0.73). Furthermore, the endothelial cell morphology showed no statistical differences between the cases where intracameral mydriatics had been used and the control cases with traditional topical dilatation at surgery. The median posterior capsule opacification fraction was 9 % in the TM group vs. 7.5 % in the intracameral mydriatics group (P=0.8). Similarly, the median severity grade of the posterior capsule opacification was 0.12 vs. 0.10 (P=0.7). Two patients in each group had YAG laser capsulotomy (P=1.0). A hydrophobic acrylic intraocular lens (MA60BM, Alcon Laboratories, Fort Worth, TX) was implanted in all cases in this study. The posterior capsule opacification scorings are in accordance with the results of other studies using the POCOman program, hydrophobic acrylic intraocular lenses and similar or shorter time for follow up (Kang, Choi et al. 2009; Ronbeck, Zetterstrom et al. 2009). Also, the rate of YAG capsulotomy in the present study was similar to reported rates from previous studies done with a comparable follow up times and acrylic hydrophobic lenses (Boureau, Lafuma et al. 2009; Boureau, Lafuma et al. 2009; Ronbeck, Zetterstrom et al. 2009). Studies concerning corneal endothelial cell loss predominantly have follow up times of a year or less and there is a wide range in reported corneal endothelial cell loss after cataract surgery (Werblin 1993; Dick, Kohnen et al. 1996; Mathys, Cohen et al. 2007). However, it is stated that there is a progressive corneal endothelial cell loss after cataract surgery that exceeds the physiological cell loss (Lesiewska-Junk, Kaluzny et al. 2002). In the present study, the 6 year corneal endothelial cell loss appears to be comparable with other studies with longer follow up times ] (Werblin 1993; Dick, Kohnen et al. 1996) (Lesiewska-Junk, Kaluzny et al. 2002). In summary, the study showed that the concept of using intracameral mydriatics in phacoemulsification cataract surgery is safe, also in a long perspective. 2.1.13 Epinine Other candidate substances for intracamral use have also been evaluated. In 2009, we performed a study of intracamerally injected N-methyl-3,4-dihydroxyphenylamine (epinine) to phenylephrine in a porcine eye model involving 112 eyes from newly slaughtered pigs (Lundberg and Behndig 2009). Epinine is an adrenergic substanse that also shows dopaminergic properties (Pyman 1909) (Barger and Dale 1910). Epinine is known to stimulate all six known receptors in cardiovascular tissues: 1, 2, 1, 2, DA1 and DA2 (Itoh 1991), and can be regarded as one of the most unspecific adrenergic/dopaminergic stimulators in this respect. In the study, after contracting the pupils with acetylcholine, 0.15 mL epinine or phenylephrine 0.3%, 1.5%, or 3.0% was given as an intracameral injection. Interestingly, epinine was significantly more potent than phenylephrine at equal concentrations. Similar results have also been demonstrated for related topical substances: ibopamine, an ester of epinine, is hydrolyzed to epinine during its passage through the cornea and exerts its pharmacological effects within the eye as epinine (Soldati, Gianesello et al. 1993). Topical ibopamine is routinely used as a mydriatic in some countries due to its interesting pharmacological profile: 2% ibopamine is a more potent mydriatic than 10% phenylephrine (Marchini, Babighian et al. 2003), and the mydriatic effect is reversed within 4 hours (Gelmi, Palazzuolo et al. 1989), making ibopamine the most short-acting and most 160 Cataract Surgery effective topical mydriatic agent studied this far. Given these circumstances, we think epinine cold be a promising candidate substance for intracameral injection to achieve mydriasis in cataract surgery. A B Intracameral Mydriatics in Cataract Surgery 161 C Fig. 4. The figure shows the increase in pupil size in porcine eyes after an intracameral injection of 150µl epinine hydrochloride (grey circles) or phenylephrine hydrochloride (white squares): 0.3% (4A) 1.5% (4B) and 3% (4C). Epinine has a more pronounced mydriatic effect at all concentrations. 2.1.14 Isoprenaline In 2011, we compared the mydriatic effect of intracamerally injected isoprenaline (a - receptor stimulator) plus phenylephrine to phenylephrine alone and to epinephrine in a porcine eye model with 89 intact porcine eyes; 0.3% isoprenaline and 0.15 ml 3.0% phenylephrine were injected sequentially in the mentioned or the reverse order. The control groups were treated with 0.025% epinephrine intracamerally or placebo. Phenylephrine injected after isoprenaline had a larger mydriatic effect than epinephrine, but without isoprenaline pretreatment, the mydriatic effect of phenylephrine was significantly smaller than that of epinephrine. Isoprenaline also showed a small mydriatic effect of its own. The -receptor stimulator isoprenaline enhances the mydriatic effect of intracameral phenylephrine, indicating a role for the -receptor in the mydriatic response. Mydriasis mediated by -receptors may explain why non-specific adrenergic stimulators such as epinine and epinephrine can have larger mydriatic effects than the specific -receptor stimulator phenylephrine (Janbaz, Lundberg et al. 2011). 2.2 Adrenergic receptors Phenylephrine, commonly used as an intracameral mydriatic, is characterized as a specific -receptor agonist. In rats and rabbits, it has been shown that the alpha(1A)-adrenoceptor is the chief mediator of the adrenergic mydriatic effects of the iris dilator muscle (Yu and Koss 2002; Yu and Koss 2003), but the mydriatic effect from an adrenergic substance may still be a 162 Cataract Surgery bit more complex; as an example, stimulation of iris -receptors can cause a relaxation of the pupil sphincter (Toda, Okamura et al. 1999). The study of Myers and Shugar indicates that epinephrine may be a more potent mydriatic agent than phenylephrine when injected intracamerally (Myers and Shugar 2009), and indeed, epinephrine has a larger affinity for the -receptor than phenylephrine (Mishima 1982). Accordingly, we have shown in a porcine eye model that the -receptor stimulator isoprenaline fortifies mydriasis from intracameral phenylephrine (Janbaz, Lundberg et al. 2011), which further suggests a role for the -receptor in the mydriatic response. Mydriasis mediated by -receptors may explain why non-specific adrenergic stimulators such as epinephrine can have larger mydriatic effects than the specific -receptor stimulator phenylephrine. Epinine has a broad spectrum of adrenergic and dopaminergic effects (Itoh 1991), and the fact that epinine stimulates all adrenergic receptors, including the -receptor (Itoh 1991) may contribute to a mydriatic effect superior to that of phenylephrine. Fig. 5. The increase in pupil size in porcine eyes after an intracameral injection of 0.15 ml 0.025% epinephrine (E; n=20), Balanced Salt Solution (BSS; n=26), 0.3% isoprenaline followed by 3.0% phenylephrine (IP; n=21) or the latter two in the reversed order (PI; n=22), means and standard errors of the mean. The mydriatic effect of phenylephrine is significantly enhanced after pretreatment with isoprenaline (p<0.05 from 30-60 s), making it even larger than that of epinephrine (p<0.05 at 30 s; p<0.01 at 45-90 s). (It is worth noting that due to logistic reasons, we were unable to receive the porcine eyes within 24 hours in this study, as opposed to in the epinine material (see 2.1.8) Therefore, the mydriatic responses in this study were generally smaller, but still fully measurable and possible to quantify and compare between the groups.) Intracameral Mydriatics in Cataract Surgery 163 2.3 Using intracameral mydriatics in intraoperative floppy iris syndrome (IFIS) Intraoperative floppy iris syndrome (IFIS) is a condition often associated with systemic medication with adrenergic receptor antagonists for benign prostatic hyperplasia. The substances most often discussed are tamsulosin, terazosin, doxazosin and alfuzosin. Of these, tamsulosin predominates in the literature. IFIS was first described and defined in 2005 as a clinically observed triad: fluttering and billowing of the iris stroma, tendency for iris prolapse, and pupil constriction. As any cataract surgeon will realize, such conditions will make the surgical procedure more difficult and increase the risk for complications. The presumed mechanism by which tamsulosin causes IFIS is by blocking receptors in the iris dilator muscle, and thereby preventing mydriasis during cataract surgery. Certain measures can be taken to reduce the risk of surgical complications in patients with IFIS, including iris hooks, preoperative topical atropine (Masket and Belani 2007), and – perhaps most interesting in this context - intracameral phenylephrine or epinephrine (Gurbaxani and Packard 2007; Masket and Belani 2007). Manvikar et al first described the use of intracameral phenylephrine to enhance mydriasis in patients with IFIS (Manvikar and Allen 2006). In their series of 32 cases on tamsulosin medication, the degree of IFIS varied among cases: 53% eyes had good mydriasis preoperatively from topical mydriatics but of these 43% showed intraoperative pupil constriction. Thirty- eight percent had semi-dilated pupils, and 9% had poor preoperative dilation. Intracameral phenylephrine, when needed, was efficient in dilating the insufficiently dilated pupils. It is well known that pupil sizes get generally smaller with age. It has been demonstrated, however, that there is no difference in - adrenoceptor sensitivity in the elderly and the young, and thus, age related miosis is not attributable to an alteration in the iris -receptors with age (Buckley, Curtin et al. 1987). Takmaz and Can published a large material in 2007, where the incidence of IFIS was determined to be 1.6% in the whole material of 858 eyes, and in no less than 14 of the 18 eyes of patients using tamsulosin (77.8%). Intracameral epinephrine was effective in preventing intraoperative miosis in the IFIS cases (Takmaz and Can 2007). A similar frequency of IFIS - just above 1% - has been reported also by other groups (Oshika, Ohashi et al. 2007; Keklikci, Isen et al. 2009). Gurbaxani and Packard showed in 2007 in a series of seven cases who were on systemic tamsulosin for benign prostatic hyperplasia that intracameral phenylephrine gave a significant reduction in iris mobility and fluttering, as well as a sustained mydriasis, in accordance with most other reports on intracameral mydriatics (Lundberg and Behndig 2003; Behndig and Eriksson 2004; Lundberg and Behndig 2007; Myers and Shugar 2009). In a retrospective material by Chen et al (Chen, Kelly et al. 2010), the incidence of IFIS among patients operated by resident physiciancs was 29.6% among patients taking tamsulosin, and more common among patients with a preoperative dilated pupil diameter of less than 6.5 mm. The authors concluded from their findings that the use of intracameral lidocaine- epinephrine did not reduce the incidence of IFIS. To conclude, most authors agree that although intracameral adrenergics may not affect the incidence of IFIS per se, the enlargement of the pupils obtained in these difficult cases is still of benefit for the surgical handling and outcome. The published data support the intuitive impression that adrenergic substances at high doses should be beneficial in cases where the iris has an insufficient muscle tone, as in IFIS. 2.4 Pharmacokinetics of intracameral mydriatics Generally, diffusion through the cornea is considered to be the main penetration route for topically applied drugs (Mishima 1981; Grass and Robinson 1988), and the corneal 164 Cataract Surgery epithelium is considered to be the main barrier (Sieg and Robinson 1976; Mishima 1981; Grass and Robinson 1988). Topically applied drugs generally penetrate the cornea slowly, with aqueous peak times ranging from 0.7 hours to 2.2 hours for various substances (Mishima 1981; Grass and Robinson 1988). For topically applied mydriatics the slow penetration through the cornea means a slow mydriatic onset (Lovasik 1986; Chien and Schoenwald 1990). For example, the peak mydriatic effect for cyclopentolate is at 30 minutes (Haaga, Kaila et al. 1998) and for phenylephrine 75 minutes (Matsumoto, Tsuru et al. 1982). In addition the bioavailability is limited for topically administered substances, which means a significant proportion of the drug will be absorbed systemically (Doane, Jensen et al. 1978; Kaila, Huupponen et al. 1989; Haaga, Kaila et al. 1998). Injecting a substance directly intracamerally will increase its bioavailability substantially, and accordingly decrease the systemic absorption. The onset of the effect will generally be very rapid after intracameral injection. Below, the research fields of intracameral pharmacokinetics will be briefly exemplified by lidocaine and phenylephrine. 2.4.1 Lidocaine In a study from 1998, we determined the intracameral concentrations of lidocine after topical administration or intracameral injection (Behndig and Linden 1998). After 3 drops of topical lidocaine, the aqueous humour lidocaine concentration was 1.4±0.5 µg/ml and with 6 drops, 4.3±1.5µg/ml. With an intracameral injection, a concentration of 341.8 +/- 152.6 µg/ml was reached. We concluded that measurable amounts of lidocaine entered the anterior chamber in topical anesthesia, and that more entered when more drops were given. It is likely that concentrations in this range could anesthetize the iris, but they are far lower than the concentrations after an intracameral injection. This is probably the reason why the mydriatic effect from topical anesthetics is very minute - although it is indeed detectable and quantifyable with sensitive methods (Behndig 2007). Thus, topically administered lidocaine is found in low, but likely pharmacologically effective levels in the aqueous humor (Behndig and Linden 1998), and it has a measurable direct mydriatic and cycloplegic effect, at least in eyes with pale (blue) irides and less pigment binding of the substance (Behndig 2007). Since anesthetic agents lack adrenergic or anticholinergic properties, these mydriatic and cycloplegic effects can be ascribed a paralytic effect on the iris, analogous to the marked pupil dilation seen after intracameral lidocaine (Cionni, Barros et al. 2003). In the beforementioned study, the lidocaine measured concentrations after an intracameral injection were about 10 times lower than what could be expected from simple dilution of the aqueous humor, meaning that just below 10 % of the injected lidocaine was found in the aqueous after 2 minutes. The rapid increase in anterior chamber volume and pressure upon injecting a volume of 100 µl might lead to diffusion of aqueous (and lidocaine) into the posterior chamber. An unknown proportion of the drug may also bind to iris pigment, as has been shown to occur for the related substance cocaine, and also for other drugs. 2.4.2 Phenylephrine A dose-response study for intracameral phenylephrine from 2010 (Behndig and Lundberg 2010) showed that phenylephrine when injected intracamerally in human subjects has a rather moderate mydriatic effect at low concentrations and that the effect is very similar in concentrations ranging from 0.015-0.5%. Higher concentrations, however, (1.5 or 3.0%) give significantly larger pupils. Noticeably, a similar lack of dose-response relationship has been Intracameral Mydriatics in Cataract Surgery 165 noted by several investigators for topical phenylephrine when comparing 2.5% to 10% (Weiss, Weiss et al. 1995; Tanner and Casswell 1996; Motta, Coblentz et al. 2009). Applying experimental bioavailability data (Mishima 1981) and assuming an aqueous humor volume of 160 µl (Jonsson, Markstrom et al. 2006) and a dose of three 37µl drops (Behndig and Linden 1998), three drops of 2.5 -10% would give intracameral doses of 0.14 and 0.57 mg phenylephrine, respectively, which is in the same range as the four lower concentrations in the dose-response study (0.02 mg – 0.73 mg). One point five and 3.0% would thus give 3.9 and 7.7 times higher intracameral phenylephrine doses, respectively, than a standard "maximum dilatation" regimen involving 3 drops of phenylephrine 10%. The effects of such high doses of phenylephrine have never been studied in humans, since the maximum recommendable topical dose is limited by potential systemic side effects (Hakim, Orton et al. 1990; Ogut, Bozkurt et al. 1996; Elibol, Alcelik et al. 1997; Lundberg and Behndig 2003), but it appears that increasing the dose of phenylephrine further would increase also the mydriatic effect beyond what can be reached with the standard topical "maximum dilatation". It may also be of interest to note that a lack of dose-response relationship similar to that of intracameral phenylephrine has been noted also for intracameral epinephrine in dilutions ranging from 0.00025% to 0.004% (Liou and Chen 2001). Fig. 6. The increase in pupil size after different concentrations of intracameral phenylephrine in cataract patients. Note that the mydriatic effect, including the time course, is very similar in concentrations ranging from 0.015-0.5% (0.15-5.0 mg/ml). At higher concentrations, 1.5 or 3.0%, a larger mydriatic effect is seen. The rather weak effect of phenylephrine at low doses is a bit puzzling given that the - receptors of the iris dilator are considered to be the most important mediators of the adrenergic mydriatic response (Yu and Koss 2002; Yu and Koss 2003). The binding of 166 Cataract Surgery phenylephrine to the -receptor is rather weak - less than 1/5 of that for epinephrine (Besse and Furchgott 1976). This may in part - but not fully - explain why comparably high doses of phenylephrine are required to achieve mydriasis. Although phenylephrine has a high specificity for the -receptor, it may not be 100% specific (Mishima 1982), and at very high concentrations such as when using intracameral mydriatics, stimulation of other receptors, for example the -receptor, could also be speculated to contribute to the mydriatic effect. 2.5 Preparation of intracameral mydriatics It was early noted that sodium bisulfite-containing solutions of epinephrine damaged the corneal endothelium (Hull, Chemotti et al. 1975). Solutions containing sodium bisulfite are therefore usually not recommended for intracameral use, although some authors claim they may be safe from an endothelial perspective if sufficiently diluted (Hull, Chemotti et al. 1975; Hull 1979). Epinephrine per se is not toxic to the corneal endothelium (Liou, Chiu et al. 2002), but bisulfite-free preparations of epinephrine may not always be easy to purchase in different countries (Myers and Edelhauser 2011). Another putative disadvantage of several adrenergic substances, including epinephrine, is their instability at a neutral pH, which often means they may need to be prepared freshly on a daily basis in clinical routine use. A commercially available eye drop containing 0.5% tropicamide and 0.5% phenylephrine hydrochloride, with addition of benzalkonium chloride, epsilon-amino capronic acid, boric acid, chlorbutanol and pH-adjusting reagents has recently been described as safe for intracameral use by a Japanese group (Mori, Miyai et al. 2010). Else, it is not advisable to try preparations for topical use intracamerally (Hull 1979), and ex tempore preparations are usually required for intracameral mydriatics, as we still lack commercially available preparations (Lundberg and Behndig 2003; Myers and Shugar 2009). Soong et al, in their publication from 2006 (Soong, Soultanidis et al. 2006), advocated the use of an intracameral cocktail prepared aseptically in the operating room from minims of cyclopentolate hydrochloride 1% phenylephrine hydrochloride 10% and 0.5 mL preservative-free lignocaine hydrochloride 2%. The substances were diluted to final concentrations of 0.1% cyclopentolate, 1.5% phenylephrine and 1.0% lignocaine. In the studies from our group, as well as in our clinical routine, the sterile solutions of intracameral mydriatics are prepared by the Product and Laboratory Department of the Swedish Pharmacy (Apoteksbolaget AB) from sterile salts of the mydriatic and anesthetic substances. In our current routine this means phenylephrine hydrochloride 15 mg and lidocaine hydrochloride 10 mg, with addition of Sodium edetase 1 mg, boric acid 3,85 mg (for isotony) and aqua injectabile ad 1 ml. The sterile solution is supplied in 10 ml airtight glass containers with rubber membranes to allow for use in multiple patients during the same day of surgery. Unopened containers can be used for up to 3 months. 3. Conclusion In the development of today's highly efficient routines for cataract surgery, the concept of intracameral mydriatics definitely has a place. From our calculations, the time a patient spends in an operating clinic during a visit for a routine cataract operation with traditional topical mydriatics for pupil dilatation consists of 82% waiting for the pupil to dilate and 18% being operated. Based on the available data, we can safely conclude that intracameral mydriatics comprise a safe and efficient alternative to traditional topical mydriatics, with time saving and simplifying potentials. Intracameral Mydriatics in Cataract Surgery 167 4. References Antcliff, R. J. and D. R. Trew (1997). "The maintenance of per-operative mydriasis in phacoemulsification with topical diclofenac sodium." Eye 11(( Pt 3)): 389-391. Artzen, D., M. Lundstrom, et al. (2009). "Capsule complication during cataract surgery: Case-control study of preoperative and intraoperative risk factors: Swedish Capsule Rupture Study Group report 2." J Cataract Refract Surg 35(10): 1688-1693. Backstrom, G. and A. Behndig (2006). "Redilatation with intracameral mydriatics in phacoemulsification surgery." Acta Ophthalmol Scand 84(1): 100-104. Ball, J. L. and G. D. Barrett (2006). "Prospective randomized controlled trial of the effect of intracameral vancomycin and gentamicin on macular retinal thickness and visual function following cataract surgery." J Cataract Refract Surg 32(5): 789-794. Barger and Dale (1910). J. Physiol. 41: 19. Behndig, A. (2007). "Effects on pupil size and accommodation from topical lidocaine hydrochloride and tetracaine hydrochloride." J Ocul Pharmacol Ther 23(6): 591-598. Behndig, A. and A. Eriksson (2004). "Evaluation of surgical performance with intracameral mydriatics in phacoemulsification surgery." Acta Ophthalmol Scand 82(2): 144-147. Behndig, A. and C. Linden (1998). "Aqueous humor lidocaine concentrations in topical and intracameral anesthesia." J Cataract Refract Surg 24(12): 1598-1601. Behndig, A. and B. Lundberg (2010). "Mydriatic response to different concentrations of intracameral phenylephrine in humans." J Cataract Refract Surg 36(10): 1682-1686. Bender, L., D. J. Spalton, et al. (2004). "POCOman: new system for quantifying posterior capsule opacification." J Cataract Refract Surg 30(10): 2058-2063. Besse, J. C. and R. F. Furchgott (1976). "Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta." J Pharmacol Exp Ther 197(1): 66-78. Biro, Z., Z. Balla, et al. (2006). "Change of foveal and perifoveal thickness measured by OCT after phacoemulsification and IOL implantation." Eye. Boureau, C., A. Lafuma, et al. (2009). "Incidence of Nd:YAG laser capsulotomies after cataract surgery: comparison of 3 square-edged lenses of different composition." Can J Ophthalmol 44(2): 165-170. Boureau, C., A. Lafuma, et al. (2009). "Cost of cataract surgery after implantation of three intraocular lenses." Clin Ophthalmol 3: 277-285. Buckley, C., D. M. Curtin, et al. (1987). "Ageing and alpha 1 adrenoceptors in the iris." Eye 1(( Pt 2)): 211-216. Camparini, M., P. Cassinari, et al. (2001). "ETDRS-fast: implementing psychophysical adaptive methods to standardized visual acuity measurement with ETDRS charts." Invest Ophthalmol Vis Sci 42(6): 1226-1231. Cantrell, M. A., H. R. Bream-Rouwenhorst, et al. (2008). "Intraoperative floppy iris syndrome associated with alpha1-adrenergic receptor antagonists." Ann Pharmacother 42(4): 558-563. Chen, A. A., J. P. Kelly, et al. (2010). "Pharmacologic prophylaxis and risk factors for intraoperative floppy-iris syndrome in phacoemulsification performed by resident physicians." J Cataract Refract Surg 36(6): 898-905. 168 Cataract Surgery Chien, D. S. and R. D. Schoenwald (1990). "Ocular pharmacokinetics and pharmacodynamics of phenylephrine and phenylephrine oxazolidine in rabbit eyes." Pharm Res 7(5): 476-483. Ching, H. Y., A. C. Wong, et al. (2006). "Cystoid macular oedema and changes in retinal thickness after phacoemulsification with optical coherence tomography." Eye 20(3): 297-303. Cionni, R. J., M. G. Barros, et al. (2003). "Cataract surgery without preoperative eyedrops." J Cataract Refract Surg 29(12): 2281-2283. Classe, J. G. (1980). "Epinephrine maculopathy." J Am Optom Assoc 51(12): 1091-1093. Dick, H. B., T. Kohnen, et al. (1996). "Long-term endothelial cell loss following phacoemulsification through a temporal clear corneal incision." J Cataract Refract Surg 22(1): 63-71. Doane, M. G., A. D. Jensen, et al. (1978). "Penetration routes of topically applied eye medications." Am J Ophthalmol 85(3): 383-386. Duffin, R. M., T. H. Pettit, et al. (1983). "2.5% v 10% phenylephrine in maintaining mydriasis during cataract surgery." Arch Ophthalmol 101(12): 1903-1906. Edwards, M., S. Rehman, et al. (1997). "Discharging routine phacoemulsification patients at one week." Eye 11(( Pt 6)): 850-853. Elibol, O., T. Alcelik, et al. (1997). "The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants." Acta Ophthalmol Scand 75(2): 178-180. Fraunfelder, F. T. and S. M. Meyer (1985). "Possible cardiovascular effects secondary to topical ophthalmic 2.5% phenylephrine." Am J Ophthalmol 99(3): 362-363. Fraunfelder, F. T. and A. F. Scafidi (1978). "Possible adverse effects from topical ocular 10% phenylephrine." Am J Ophthalmol 85(4): 447-453. Gelmi, C., A. Palazzuolo, et al. (1989). "Pupillographic evaluation of the mydriatic effect of ibopamine solution." Int J Clin Pharmacol Ther Toxicol 27(7): 346-351. Grass, G. M. and J. R. Robinson (1988). "Mechanisms of corneal drug penetration. I: In vivo and in vitro kinetics." J Pharm Sci 77(1): 3-14. Gurbaxani, A. and R. Packard (2007). "Intracameral phenylephrine to prevent floppy iris syndrome during cataract surgery in patients on tamsulosin." Eye (Lond) 21(3): 331- 332. Haaga, M., T. Kaila, et al. (1998). "Systemic and ocular absorption and antagonist activity of topically applied cyclopentolate in man." Pharmacol Toxicol 82(1): 19-22. Hakim, O. J., R. B. Orton, et al. (1990). "Topical 2.5% and 5% phenylephrine: comparison of effects on heart rate and blood pressure." Can J Ophthalmol 25(7): 336-339. Hempel, S., P. Senn, et al. (1999). "[Perioperative circulatory side effects of topical 5% phenylephrine for mydriasis]." Klin Monatsbl Augenheilkd 215(5): 298-304. Hull, D. S. (1979). "Effects of epinephrine, benzalkonium chloride, and intraocular miotics on corneal endothelium." South Med J 72(11): 1380-1381. Hull, D. S., M. T. Chemotti, et al. (1975). "Effect of epinephrine on the corneal edothelium." Am J Ophthalmol 79(2): 245-250. Itoh, H. (1991). "Clinical pharmacology of ibopamine." Am J Med 90(5B): 36S-42S. Intracameral Mydriatics in Cataract Surgery 169 Janbaz, C. C., B. Lundberg, et al. (2011). "Stimulation of adrenergic beta-receptors enhances mydriasis in a porcine eye model." Acta Ophthalmol. Jayadev, C. and B. K. Nayak (2007). "Pupil dilation with intracameral lidocaine during phacoemulsification." J Cataract Refract Surg 33(9): 1503; author reply 1503. Johansson, M., B. Lundberg, et al. (2007). "Optical coherence tomography evaluation of macular edema after phacoemulsification surgery with intracameral mydriatics." J Cataract Refract Surg 33(8): 1436-1441. Jonsson, M., K. Markstrom, et al. (2006). "Slit-scan tomography evaluation of the anterior chamber and corneal configurations at different ages." Acta Ophthalmol Scand 84(1): 116-120. Kaila, T., R. Huupponen, et al. (1989). "Systemic absorption of ophthalmic cyclopentolate." Am J Ophthalmol 107(5): 562-564. Kang, S., J. A. Choi, et al. (2009). "Comparison of posterior capsular opacification in heparin- surface-modified hydrophilic acrylic and hydrophobic acrylic intraocular lenses." Jpn J Ophthalmol 53(3): 204-208. Keklikci, U., K. Isen, et al. (2009). "Incidence, clinical findings and management of intraoperative floppy iris syndrome associated with tamsulosin." Acta Ophthalmol 87(3): 306-309. Klein, R., B. E. Klein, et al. (1983). "Inter-observer variation in refraction and visual acuity measurement using a standardized protocol." Ophthalmology 90(11): 1357-1359. Kolker, A. E. and B. Becker (1968). "Epinephrine maculopathy." Arch Ophthalmol 79(5): 552- 562. Lesiewska-Junk, H., J. Kaluzny, et al. (2002). "Long-term evaluation of endothelial cell loss after phacoemulsification." Eur J Ophthalmol 12(1): 30-33. Liou, S. W. and C. C. Chen (2001). "Maintenance of mydriasis with one bolus of epinephrine injection during phacoemulsification." J Ocul Pharmacol Ther 17(3): 249-253. Liou, S. W., C. J. Chiu, et al. (2002). "Effects of intraocular epinephrine on the corneal endothelium of rabbits." J Ocul Pharmacol Ther 18(5): 469-473. Liou, S. W. and C. Y. Yang (1998). "The effect of intracameral adrenaline infusion on pupil size, pulse rate, and blood pressure during phacoemulsification." J Ocul Pharmacol Ther 14(4): 357-361. Lovasik, J. V. (1986). "Pharmacokinetics of topically applied cyclopentolate HCl and tropicamide." Am J Optom Physiol Opt 63(10): 787-803. Lundberg, B. and A. Behndig (2003). "Intracameral mydriatics in phacoemulsification cataract surgery." J Cataract Refract Surg 29(12): 2366-2371. Lundberg, B. and A. Behndig (2007). "Intracameral mydriatics in phacoemulsification surgery obviate the need for epinephrine irrigation." Acta Ophthalmol Scand. Lundberg, B. and A. Behndig (2008). "Separate and additive mydriatic effects of lidocaine hydrochloride, phenylephrine, and cyclopentolate after intracameral injection." J Cataract Refract Surg 34(2): 280-283. Lundberg, B. and A. Behndig (2009). "The mydriatic effect of intracameral epinine hydrochloride." Invest Ophthalmol Vis Sci 50(11): 5336-5338. 170 Cataract Surgery Lundberg, B. and A. Behndig (2009). "Preoperative topical cyclopentolate can be omitted when using intracameral lidocaine in phacoemulsification surgery." Acta Ophthalmol 87(3): 297-299. Lundstrom, M., U. Stenevi, et al. (2002). "The Swedish National Cataract Register: A 9-year review." Acta Ophthalmol Scand 80(3): 248-257. Manvikar, S. and D. Allen (2006). "Cataract surgery management in patients taking tamsulosin staged approach." J Cataract Refract Surg 32(10): 1611-1614. Marchini, G., S. Babighian, et al. (2003). "Comparative study of the effects of 2% ibopamine, 10% phenylephrine, and 1% tropicamide on the anterior segment." Invest Ophthalmol Vis Sci 44(1): 281-289. Marsich, M. W. and M. A. Bullimore (2000). "The repeatability of corneal thickness measures." Cornea 19(6): 792-795. Masket, S. and S. Belani (2007). "Combined preoperative topical atropine sulfate 1% and intracameral nonpreserved epinephrine hydrochloride 1:4000 [corrected] for management of intraoperative floppy-iris syndrome." J Cataract Refract Surg 33(4): 580-582. Mathys, K. C., K. L. Cohen, et al. (2007). "Determining factors for corneal endothelial cell loss by using bimanual microincision phacoemulsification and power modulation." Cornea 26(9): 1049-1055. Matsumoto, S., T. Tsuru, et al. (1982). "Pharmacokinetics of topical phenylephrine hydrochloride in the normal human eye." Jpn J Ophthalmol 26(3): 338-344. Mehelas, T. J., C. R. Kollarits, et al. (1982). "Cystoid macular edema presumably induced by dipivefrin hydrochloride (Propine)." Am J Ophthalmol 94(5): 682. Meyer, S. M. and F. T. Fraunfelder (1980). "3. Phenylephrine hydrochloride." Ophthalmology 87(11): 1177-1180. Mishima, S. (1981). "Clinical pharmacokinetics of the eye. Proctor lecture." Invest Ophthalmol Vis Sci 21(4): 504-541. Mishima, S. (1982). "Ocular effects of beta-adrenergic agents. XII Jules Stein Lecture. ." Surv Ophthalmol 27: 187-208. Miyake, K., E. Shirasawa, et al. (1989). "Hypotheses on the role of prostaglandins in the pathogenesis of epinephrine maculopathy and aphakic cystoid macular edema." Prog Clin Biol Res 312: 265-276. Morgado, G., P. Barros, et al. (2010). "Comparative study of mydriasis in cataract surgery: topical versus Mydriasert versus intracameral mydriasis in cataract surgery." Eur J Ophthalmol 20(6): 989-993. Mori, Y., T. Miyai, et al. (2010). "Intraoperative mydriasis by intracameral injection of mydriatic eyedrops: in vivo efficacy and in vitro safety studies." Clin Experiment Ophthalmol. Motta, M. M., J. Coblentz, et al. (2009). "Mydriatic and cardiovascular effects of phenylephrine 2.5% versus phenylephrine 10%, both associated with tropicamide 1%." Ophthalmic Res 42(2): 87-89. Myers, W. G. and H. F. Edelhauser (2011). "Shortage of bisulfite-free preservative-free epinephrine for intracameral use." J Cataract Refract Surg 37(3): 611. Intracameral Mydriatics in Cataract Surgery 171 Myers, W. G. and J. K. Shugar (2009). "Optimizing the intracameral dilation regimen for cataract surgery: prospective randomized comparison of 2 solutions." J Cataract Refract Surg 35(2): 273-276. Nikeghbali, A., K. G. Falavarjani, et al. (2008). "Pupil dilation with intracameral lidocaine during phacoemulsification: Benefits for the patient and surgeon." Indian J Ophthalmol 56(1): 63-64. Nikeghbali, A., K. G. Falavarjani, et al. (2007). "Pupil dilation with intracameral lidocaine during phacoemulsification." J Cataract Refract Surg 33(1): 101-103. Ogut, M. S., N. Bozkurt, et al. (1996). "Effects and side effects of mydriatic eyedrops in neonates." Eur J Ophthalmol 6(2): 192-196. Oshika, T., S. Amano, et al. (2001). "Current trends in cataract and refractive surgery in Japan: 1999 survey." Jpn J Ophthalmol 45(4): 383-387. Oshika, T., Y. Ohashi, et al. (2007). "Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist." Am J Ophthalmol 143(1): 150-151. Pyman (1909). J. Chem. Soc. 95(1266): 1610. Ronbeck, M., C. Zetterstrom, et al. (2009). "Comparison of posterior capsule opacification development with 3 intraocular lens types: five-year prospective study." J Cataract Refract Surg 35(11): 1935-1940. Sieg, J. W. and J. R. Robinson (1976). "Mechanistic studies on transcorneal permeation of pilocarpine." J Pharm Sci 65(12): 1816-1822. Soldati, L., V. Gianesello, et al. (1993). "Ocular pharmacokinetics and pharmacodynamics in rabbits of ibopamine, a new mydriatic agent." Exp Eye Res 56(2): 247-254. Soong, T., M. Soultanidis, et al. (2006). "Safety of intracameral mydriasis in phacoemulsification cataract surgery." J Cataract Refract Surg 32(3): 375-376. Sourdille, P. and P. Y. Santiago (1999). "Optical coherence tomography of macular thickness after cataract surgery." J Cataract Refract Surg 25(2): 256-261. Takmaz, T. and I. Can (2007). "Clinical features, complications, and incidence of intraoperative floppy iris syndrome in patients taking tamsulosin." Eur J Ophthalmol 17(6): 909-913. Tanner, V. and A. G. Casswell (1996). "A comparative study of the efficacy of 2.5% phenylephrine and 10% phenylephrine in pre-operative mydriasis for routine cataract surgery." Eye 10(( Pt 1)): 95-98. Thomas, J. V., E. S. Gragoudas, et al. (1978). "Correlation of epinephrine use and macular edema in aphakic glaucomatous eyes." Arch Ophthalmol 96(4): 625-628. Toda, M., T. Okamura, et al. (1999). "Mechanisms underlying the neurogenic relaxation of isolated porcine sphincter pupillae." Exp Eye Res 68(4): 505-512. Weiss, J. S., J. N. Weiss, et al. (1995). "The effects of phenylephrine 2.5% versus phenylephrine 10% on pupillary dilation in patients with diabetes." Retina 15(2): 130-133. Werblin, T. P. (1993). "Long-term endothelial cell loss following phacoemulsification: model for evaluating endothelial damage after intraocular surgery." Refract Corneal Surg 9(1): 29-35. 172 Cataract Surgery Yi, Q., S. J. Flanagan, et al. (2001). "Trends in health service delivery for cataract surgery at a large Australian ophthalmic hospital." Clin Experiment Ophthalmol 29(5): 291-295. Yu, Y. and M. C. Koss (2002). "alpha(1A)-adrenoceptors mediate sympathetically evoked pupillary dilation in rats." J Pharmacol Exp Ther 300(2): 521-525. Yu, Y. and M. C. Koss (2003). "Studies of alpha-adrenoceptor antagonists on sympathetic mydriasis in rabbits." J Ocul Pharmacol Ther 19(3): 255-263.
Pages to are hidden for
"Intracameral mydriatics in cataract surgery"Please download to view full document


text:
|Property type
|Minimum Stay
|3 - 5 nights
Your very own, top-floor, Buffalo Ridge condo has fabulous mountain views! This spacious (1052 sq.ft.) three bedroom, two bath condo has spectacular views of the Continental Divide, Keystone ski slopes, the Ten Mile Range and Lake Dillon.
Five major ski areas are located within 10-15 miles of this beautiful condo. The Summit County Stage (free bus service) stops at the condo's entrance and provides totally free transportation to Breckenridge, Keystone, Copper Mountain and A-Basin. In addition, Vail/Beaver Creek is about 30 minutes west on I-70. This awesome alpine area is a skier's and hiker's dream come true!
Your lodge-like condo is surrounded by the beauty and wildlife of the Arapahoe National Forest and the Eagle's Nest Wilderness Area. Two hiking trailheads are 1/4 mile from the back doorstep! Imagine yourself rafting the Colorado River or going horseback riding among the beautiful pine and aspen forest.
This condo will accommodate eight people. The Master Suite is furnished with a queen bed. Bedroom #2 also has a queen bed. A spiral staircase leads to the loft (Bedroom #3) which features a queen bed and bunk beds. Please keep in mind that this is a no-smoking condo.
The fully-equipped kitchen is well stocked with all the basics to easily satisfy your cooking needs!
This home-away-from-home has privacy, views and that popular 'cabin feel'. The Colorado mountain decor features a large, woodburning fireplace, cathedral ceilings, and sliding doors opening onto a deck. A generous supply of firewood is provided. We just added a 37' flat screen TV for your enhanced entertainment!
We are happy to report that we can now offer our guests WiFi Internet connection at no extra charge.
Also, our guests really enjoy having the choice of three conveniently located clubhouses--all at no additional cost! The three clubhouses have a heated swimming pool, hot tub, sauna, pool table and game room. One clubhouse also features a racquetball court, and there is even a tennis court for the summer enthusiast.
Covered parking for your car and on-site laundry facilities will also help to make your vacation easier and more comfortable.
Your hosts are Lonni and Steve Bell, the condo's owners. We do want you to be aware that, since the condo is on the third floor, there are stairs to climb. However, a convenient back entrance cuts the climb in half for loading and unloading your car, and the top floor view is absolutely the best in Summit County!
RESERVATION INFORMATION: For your convenience, we now offer a choice of Visa, Mastercard or personal check. To confirm your reservation, we require a deposit for two night's lodging. Payment of the balance is due 30 days prior to your planned arrival date. A fully refundable $200 security/damage deposit is also required; your refund will be issued within two weeks of your departure.
Keywords: Condominium
Even though we live in Lawrence, Kansas, we are big Colorado fans. Steve loves to camp and go exploring in these fantastic mountains, and Lonni loves the scenery and the wildlife. We both love the history of the area--the mountain men, the miners, the pioneers, the Native tribes and the fascination of the old West.
Lonni and Steve Bell purchased this condo in 1997
Our condo is truly our second home; when the temperature is 100 degrees in Kansas, we like to be in Summit County with temperatures in the 70s! There is always something to do in any season. In the summer we enjoy Farmer's Markets, free concerts at the Dillon Ampitheatre and scenic drives. In the fall we have fun at Oktoberfest festivals in Vail or Breckenridge, along with drives to view the glorious fall foliage. Of course, winter offers the most awesome skiing and snowboarding anywhere!
Nevertheless, our favorite thing to do is sit by the fire in our condo with a cup of coffee or glass of wine and look out at our spectacular view. We often see the red fox trot by (usually early in the morning or around dusk), or maybe we'll catch a glimpse of the moose down below in the old beaver ponds. Whatever, or whenever, we love our condo, and we know you will, too!
We're here every year for 5 weeks. Our grandkids visit and we ski most days. Love the condo.
we had an awesome time staying in your condo! It was in a perfect location and our kids enjoyed the amenities! Thanks for everything
We had the best time at this condo. Very roomy, open floor plan, which allowed our family and another family to visit freely. Spacious, with an excellent kitchen set up. We had everything we needed to cook in the condo, we even made homemade tortillas for breakfast burritos! Great place for kids, loft was fun sleeping/entertainment area to allow kids a space for 'kid time'. Our teen didn't even mind bunking with the little ones, as he had is own queen size bed. Clubhouse was a short walk from condo, lots of stairs but a good way to acclimate to the altitude :)
We enjoyed this condo for one glorious week in the summer with our adult children and spouses. This confortable condo was an ideal place for relaxing, enjoying the beautiful mountain vistas and then launching out to check out the MANY wonderful activities in Summit County - we took in rafting, cycling, hiking, shopping and hanging out in the local restaurants and microbreweries and could have stayed another week.....there was so much to do and everything was so much fun! We highly recommend Steve and Lonni's condo for the comfort and location! Would love to return for another visit - it would be great any season of the year!
Beautifully decorated condo..amazing views of the beautiful mountains of Summit County..wish we could stay longer!
We stayed here for three nights and had a wonderful time! The condo was very clean and had everything we needed for our stay. The owners were great about getting me the information I needed and we loved all of their suggestions and tips about the condo, clubhouses, and activities and restaurants nearby! We will definitely be returning!!
My wife and I have been making an annual trip to Summit County every year since 1986 and we have stayed in almost all of the Wildernest area complexes at one time or another. However, eight or nine years ago we "found" this condo gem in the Buffalo Ridge complex and each year since then we have been enjoying the hospitality and comforts of this wonderful condo. Our vacations are usually 30-40 days so we have spent many, many days in this condo. We love the views, the snow on the mountains, the sunsets over the Breckenridge area, seeing the twinkling night-sking lights at Keystone. The laundry is right downstairs, and if it's busy you can always take your laundry to the clubhouse (any of the three) and do your laundry while you soak in the hot tub or swim or use the sauna. If you're there to ski you'll love the covered parking spot. Besides saving time in the morning it's always about 10F warmer in that spot than if your car were sitting out on the parking lot. The pictures speak for themselves, these aren't "old" pictures, Steve and Lonni update them almost every year because they are always updating their condo. Great TV, great selection of DVDs, free WiFi, everything works! You can compare, but you won't find a better value in Summit County. We'll be there again in January and already planning on 2014!
Gold-Medal Fishing, Sleigh Rides, Back country exploring, Georgetown Loop Steam Train rides, Historic Mines, Factory Outlet Mall includes Polo Ralph Lauren, Calvin Klein, Old Navy, Banana Republic and Chicos, among many others.
|Rate Period
|Weekend Night
Powder Ski
Feb 13 2015 - Mar 31 2015
3 night minimum stay
Spring Value
Apr 1 2015 - May 31 2015
3 night minimum stay
Jun 1 2015 - Oct 31 2015
3 night minimum stay
Nov 1 2015 - Dec 17 2015
3 night minimum stay
Dec 18 2015 - Jan 1 2016
5 night minimum stay
|$140 + Tax
|Refundable damage deposit
|Tax Rate
Payment is usually accepted in the quoted currency (USD) unless the currency and the amount is specifically agreed in advance with the owner / advertiser.

subset: commoncrawl


text: Texas State Guard Headquarters Texas State Guard Headquarters Area of Operations: Austin, Camp Mabry Subordinate Units: TXSG-HQ Role: General Staff, Personnel, Plans and Operations, Inspector General, JAG, Signal Commander: MG Jake Betty Web Site: http://www.txsg.state.tx.us Recruiter: TXSG HQ Recruiter Public Affairs Officer: COL David Erinakes Texas State Guard Headquarters, based at Camp Mabry in Austin, TX, coordinates and directs the four components of the Texas State Guard: Air Component Command (2 Wings), Army Component (6 regiments), a Maritime Regiment, and a Medical Brigade. Headquarters is made up of General Staff, Planning and Operations, Inspector General, and JAG. Our Motto: Equal to the Task


text:
Starring: Naren,Poonam Bajwa,Santhanam,Prabhu,Meena,Santhanam,MS Baskar,Sangeetha and others
Thambikottai has Naren and Poonam Bajwa in lead.The film will be based on a real incident which happened in a village near Thanjavur.It will carry a story based on the events happened in the locality.Actress Meena is also said to don a prominent role in this movie. Music is scored by D.Imaan.
Starring: Akhil, Baby Sanusha
The film is directed by Thamizhvannan and is produced under the banner Vision X media..
Akhil and Baby Sanusha are in lead..The director, who has attempted a rural subject in this film, says" As Nandhi, which is the gate keeper to Lord Shiva, the village too has certain guardians in the form of individuals which has been highlighted in this film".
Melodious numbers are scored by Bharadwaj..
Starring: Nagarjuna,Prakash Raj,Sana Khan,Ganesh,Manobala,MS Baskar and others
Director Radha Mohan known for his sensitive and touching films like Mozhi and Abhiyum Naanum is ready with his next film Payanam.
Director Lingusamy's banner 'Tirupathy Brothers' has bought the distribution rights of Payanam .. The film which is touted to be a bilingual flick (Tamil & Telugu) is a hijack drama starring Prakash Raj, Nagarjuna in prominent roles.. The film which also features Ganesh Venkatram and Sana Khan has Nagarjuna playing the role of a commando, with Prakash Raj playing a official from the Prime Minister's Office whose main agenda is to negotiate a peaceful release of the hostages.. The film which is set for release has background music scored by Praveen Mani and art by Guhan..
Starring: Nishanth,Vimal,Bharani,Anjali and others
Thoonga Nagaram is directed by debutant Gaurav who has earlier worked as an assistant to KS Ravikumar. the film casts Nishanth,Vimal and Bharani in lead roles. Anjali is the heroine.
the story is set in backdrop of madurai, while music has been scored by Sundar.C. babu.
Summary | Audio launch | MP3 songs | News | Trailer | Gallery Details
Starring: Cheran,Deepa Sha,Yugendran,YG Mahendran and others
Director Mysskin has begun work on his next film "Yutham Sei" with Cheran in the lead role. The movie will be produced by Kalpathi.S.Agoram under the banner AGS Entertainment.. Touted to be an edge-of-the-seat thriller, the film will have Debutante Deepa Sha as heroine..
The team will have many debutants, including cameraman Sathya, who was an assistant of P.C.Sriram, and music director K. Art is handled by Amaren while editing is by Gaughin..
Starring: Shiva,Madhu shalini,Black Pandi
Pathinaru is a romantic entertainer which portrays the romance between 16 and 25 years. Shiva and Madhu Shalini are playing the lead roles, while musician Darbuka Siva and small screen artiste Abhishek are seen in vital roles.
Starring: Vijay, Asin, Vadivelu, Raj Kiran and others
Vijay's Kaavalkaran movie has been renamed to Kaavalan. Kaavalan directed by Siddique features Vijay and Asin in lead roles. Kaavalan is more apt title as per director Siddique and the movie is a remake ofhis Bodyguard film from Malayalam.In the film Raj Kiran who is under threatfrom his enemies hire Vijay a bodyguard to protect his college going daughter Asin.
Starring: Pa.Vijay, Ramya Nambeesan, Kushboo, Namitha, Nasser, Vadivelu and others
Ilaignan is a period film set in the 1950s based on the script written by Kalaignar Karunanidhi. Ilaignan stars Pa. Vijay, Meera Jasmine and Remya Nambeesan in the major roles. Ilaignan is directed by Suresh Krissna with music from Vidyasagar.
Summary | Audio launch | MP3 songs | News | Trailer | Gallery Details
Check 'Nannbenda' UK & France Showtimes
"பிறவி" படத்தின் பாடலுக்காக ஆர்யா, விஷால், விஷ்ணு!
'Valiyavan' great business at box office
விஜய்-59 படத்தில் ராதிகா சரத்குமார்
'Savaale Samaali' Audio releasing on 2nd April
ருத்ரமாதேவி படத்துக்காக இளையராஜாவை சந்தித்த அனுஷ்கா
மா.கா.பா. ஆனந்த் - சிருஷ்டி டாங்கே நடிக்கும் "நவரச திலகம்"
'Uttama Villain' Telugu Version Audio Launched
ஸ்டன்ட் காட்சியில் விஜய்வசந்த் – சிருஷ்டி டாங்கே
'Kaipesi Kadhal' Movie Audio Launched
'அச்சாரம்' படத்திற்காக பாட்டெடுக்க நாங்க பட்ட பாடு!
'Ramanujan' Screened for Hon. President of India
இயக்குனர் ராம், ப்ரியாமணி நடிக்க மிஷ்கின் தயாரிக்கும் படம்
Lawrence 'Kanchana 2' Audio Releasing tomorrow
கோடை விடுமுறைக்கு வெளியாகிறது 'எலி'
Jyotika's "36 Vayadhinilae" Audio release date
ஆர்யா, விஜய் சேதுபதி நடித்த 'புறம்போக்கு' மே 1-ல் வெளியீடு
'Valiyavan' Successful Opening
ஜீவாவுடன் இணைந்து நடிக்கும் கீர்த்தி சுரேஷ்
'Valiyavan' Releasing today & Good Opening


text:
Talk:Android software development
|WikiProject Software / Computing
|(Rated B-class, Mid-importance)
|Material included in the associated project or article page was split from Android (operating system) on 13 May 2011. The page history of that page now serves as the attribution history for the contents of the associated project or article page.
"The Simple Project"[edit]
It doesn't make much sense to have Basic4Android lumped under "The Simple Project" and then say that The Simple Project is no longer active while Basic4Android is very active. Why not change the heading to "Basic4Android"? 126.96.36.199 (talk) 12:27, 15 February 2012 (UTC)
Fragmentation Section[edit]
This section needs to be both brought up to present and altered in tone from an advocatory "explaining away" of fragmentation issues to an objective reporting of the current state of affairs. Uptake of new Android versions is paralyzed due to manufacturer-specific implementations which can't be upgraded independently by users. Fragmentation is so severe that app and even Web developers are compelled to put extraordinary resources into testing and still can't reliably support all devices.
http://arstechnica.com/gadgets/2012/03/android-fragmentation-also-a-challenge-for-web-developers/ — Preceding unsigned comment added by 220.127.116.11 (talk) 15:43, 7 June 2012 (UTC)
- This is relevant to 0.9% of the customer base only. "Severe" is quite an overstatement. I have a few things to say about this.
- Web developers have been encouraged for years to use ems instead of pixels. Different screen sizes are not a problem except for the most ancient of websites.
- Android toolkit resizes at different resolutions.
- Resources in apks are at different resolution. (ldpi, mdpi, hdpi and xhdpi)
- The PC market is way more fragmented.
- As a developer I think this section is a load of selectively-researched FUD. It should go.--davidh.oz.au 05:20, 9 June 2012 (UTC)
the HyperNext issue[edit]
this section should be generic and include all such, including Caede at caede.curl.com G. Robert Shiplett 12:12, 5 November 2012 (UTC)
Merge ADB and Fastboot[edit]
Should Android Debug Bridge be merged into this article? I think so They think it's all over (talk) 19:25, 15 November 2012 (UTC)
- Done. Also merged in the article "Fastboot". If this article (Android software development) ever gets too large, the entire section "Software development tools" can be summarized and spun off to a new separate article. (I refactored the title of this talk section to include the subtitle: "Merge ADB and Fastboot".) Sparkie82 (t•c) 04:37, 28 December 2012 (UTC)
a handset emulator?[edit]
I wish that there were more on that, such as, can it be used to run Android apps on one's PC? --Jerome Potts (talk) 03:38, 18 June 2013 (UTC)
no mention of android studio?[edit]
http://developer.android.com/sdk/installing/studio.html#Updating — Preceding unsigned comment added by 126.96.36.199 (talk) 13:09, 12 February 2014 (UTC)
- There's already a separate article, Android Studio. — Dsimic (talk | contribs) 21:27, 12 February 2014 (UTC)
"officially supported": Eclipse or Android Studio ?[edit]
I am a little bit puzzled: In Sec. 1.1 someone says: "The officially supported integrated development environment (IDE) is Eclipse using the Android Development Tools (ADT) Plugin, though IntelliJ IDEA IDE (all editions) fully supports Android development out of the box" but when I visit the "Building Your First App" intro on https://developer.android.com/ it refers me to the community edition Android Studio. I am a newbie in Android development, so I would appreciate any clarification. Additionally Android Studio is labeled on its download page as "The official Android IDE" on 14. Jan. 2015. Treutwein (talk • contribs)


text:
With some help
Beauty mavens will never have to fuss over organizing another soirée again. L'occitane will plan the party for you.
Women (and men too) can now invite up to five friends and take credit for being the hostess with the mostest as the famed French brand pampers all who attend with signature beauty rituals. Ideal for bridal parties, sorority get-togethers or small office gatherings, this event is completely free of charge; and available at any of L'occitane's free standing boutiques around South Florida.
Friends Night Out Includes: A two-hour private event at the store for the host and up to five of his/her friends on the day of their choice A "Pampering Master Class" – with a choice of three themes: Skincare (mini-facials) Bodycare (signature hand massages) Fragrance (fragrance personality testing) An exclusive 10% discount during the two hour event A thank you gift for the host Refreshments, including rosé wine We would love for you to share this exciting consumer opportunity with your readers along with a free L'occitane new Limited Edition Shea October giveaway.
Done deal!
For locations: www.loccitane.com/
[1] http://www.miami.com/on-our-radar
[2] http://www.miami.com/david-beckham-canvasing-miami-again-article
[3] http://www.miami.com/13-best-photos-day-3-miami-music-week-2015-article
[4] http://www.miami.com/nightlife/wmc-close
[5] http://www.miami.com/paris-hilton-red-carpet-article
[6] http://www.miami.com/kathie-lee-gifford-boca-bachannal-article
[7] http://www.miami.com/ex-real-housewives-miami-star-arrested-article
[8] http://www.miami.com/local-contestant-039hell039s-kitchen039-article
[9] http://www.miami.com/big-bang-theory-star-jim-parsons-miami-article
[10] http://www.miami.com/dan-aykroyd-making-stops-broward-article
[11] http://www.miami.com/scott-disick-set-appear-crazy-horse-article
[12] http://www.miami.com/toni-braxton-meets-wades-benefit-article
[13] http://www.miami.com/sir-richard-branson-takes-formula-e-article
[14] http://www.miami.com/nick-zano-talks-being-florida-guy-article
[15] http://www.miami.com/victoria039s-secret-spring-break-party-article
[16] http://www.twitter.com/miamicom


text:
Elijah List
The Elijah List sends out daily prophetic words that people have supposedly received from God.By Tim McHyde
However, if you are familiar enough with the Bible and carefully compare the content and tone of the prophecies to Biblical prophecies, you may notice glaring discrepancies.
If you liked this article, you will LOVE my book, Know the Future, a comprehensive, literal explanation of end time prophecy read by over 21,000 people since 2005.
It explains more on prophecy than all this site's articles combined and is up-to-date in its 8th edition, in both softcover and ebook. Note: By buying my book you not only bless us both (yourself with understanding and me with support), but you also bless others with the new articles you enable me to write.
Tim McHyde is the founder of EscapeAllTheseThings .com and a blogger on Bible prophecy since 1999. To read more from Tim and not miss a single new article, please sign up for his free newsletter below.
Email this article to a friend
Feedback / Questions (e.g., "Tim, what does Bible prophecy mean by...").
Articles on Elijah List
Related Categories
- Back to: Ministries
- View All Categories
Tim McHyde
Don't Be Confused About Bible Prophecy Another MinuteHere's the Bible Prophecy breakthrough you've been waiting for—from two overlooked keys in the hard sayings of Jesus now made plain in the most accurate prophecy research available, because it departs from traditional "anything goes" allegorical interpretations which disregard Jesus' only statement on how to interpret Scripture correctly. (Learn these keys of Jesus in this free article...)
A Reader Comments:
"I've been searching all of my adult life for this kind of wisdom! I have listened to Irvin Baxter for 13 years and the Prophecy Club off and on for the same amount of time. I felt like I only had bits and pieces of the big picture. Then I hit the "wisdom and understanding jackpot" the next night when I typed "Prophecy" into a google search and out of all the sights that were available, I clicked on Tim's site first! It was like God pulled a needle out of a haystack for me in answer to my prayer from the day before!"


text:
Showing current 10 matches on map. See all 33 on a map.
Register to get free email alertsGet new rooms emailed to me
Average price in this area is £401 per month
33 Room Adverts
2 rooms available from £500.00 per month in Cambridge (CB4)
2 rooms available from £450.00 per month in Cambridge (CB2) - Bills inc.
Click here to Reset Your Password


text:
TWIN FALLS, Idaho — Disabled residents have found it difficult to get around the rural community of Twin Falls, but a new nonprofit group has been able to provide transportation to 1,000 residents by pursuing federal grant funding and implementing a voucher system, reported the Daily Yonder.
To read the full story, click here.
The Titan800 Retractor System is designed to meet the latest WC18 industry regulations, which take effect December 2015.
The Final Rule applies to public entities providing fixed route, dial-a-ride and complementary paratransit services. It establishes that an individual's disability cannot preclude a public transportation entity from providing full access to its service except where doing so would fundamentally alter the service.
Following unanimous approval by the SFMTA board in January, the SFMTA has worked tirelessly to meet the city's demand for this program. In just over one month, the SFMTA has processed more than 38,000 applications for the Free Muni program expansion.
The accusations stem from a human rights complaint by a rider who said a bus driver refused to lower the wheelchair ramp for her because she was using a walker and not a wheelchair. STM holds monthly meetings where they open the floor to citizens to ask questions directly to board members.
The Berkshire Regional Transit Authority Soldier On call center coordinates transportation for veterans and their families traveling to VA medical centers in Leeds, Mass. and Albany as well as Pittsfield's VA clinic. Users can also coordinate work, education and shopping trips using existing routes.
Receive latest news and stories


text:
Help me identify squash/gourd
Hi all hoping someone can help me identify this squash which potentially could be a gourd or even melon. I think it's squash or gourd as it's got prickly stems on the leaves. I planted lots of varieties this year and kind of lost track when they went in big pots so now I have this lovely plant and big fruit but no way of knowing what it is! It looks like a big fat marrow crossed with watermelon! Last two days it has started getting lumpy bits which don't look like a virus to me, look like they are meant to be on there. I've grown gourds, melons and squashes so it could be any! Mainly I need to know if it's edible as some gourds aren't! Please help! Thank you
Did you buy these seeds or is this plant a volunteer or from saved seed from last year? If it's a volunteer no one will know for sure what it is. It's definitely not a melon. If it came from bought seeds I would guess it's a decorative squash/gourd in the C. pepo species.
Hi guys I'll take some pics of the actual plant tomorrow maybe that will help. I planted bought seeds and volunteers too, so many varieties! Next year they will be back in the allotment but this year life got in the way so into pots they went and I lost track!
Because the plant is staying put and not running around, I don't think it's a decorative gourd. The texture of the rind and the leaves suggest yellow squash lineage. When the plant sets another fruit, harvest it as a summer squash and see how it tastes.
If I had your strange squash I'd let it mature taste it as a winter squash, but don't get your hopes up. In my experience, four out of five times they are dogs, but fun to grow.
When you dabble in open-pollinated cucurbits, some off types are part of the scene.
Agree with planatus. Since you planted volunteers you will likely never know its name as it probably doesn't have one. It is a result of previous cross-pollination of unknown plants. But the odds are it is edible, just not worth the space it is taking up in taste.
As all the previous "help me ID this squash" posts here show, saving squash seeds and growing volunteers very seldom turns out to be worthwhile. It cross-pollinates far too easily to faithfully reproduce from seed without active intervention early in the previous season.


text:
Welcome to St. Paul's online! We are thrilled you have chosen to visit us on the web. We welcome you to join us on our journey as we seek to serve the Christ in all.
Shrove Tuesday Fundraiser
What: Fundraiser for Midlands Humane Society
Where: St. Paul's Episcopal Church, 22 Dillman Drive (corner of Kanesville and Simms)
When: Tuesday, February 17, 6:00-8:00 p.m., Parish Hall on the lower level
Cost: Donation of supplies to the Midlands Humane Society
Contact: Fr. Aaron Hudson, 712-323-7188
Items to donate:
Dog and cat toys
Soft pet beds of all sizes
Non-clumping clay cat litter
Toilet paper
Paper towels
Office supplies
Dawn dish soap
Trinity Institute 2015
How can we take on economic inequality as a community? Find out at TI2015 this January 22-24 at St. Paul's. This weekend conference provides practical ways to take on this complex issue. Register or find more information at www.iowaepiscopal.org
Epiphany Conversations
What is Jesus' Good News for you?
What motivates you to be a disciple in today's world and use your gifts in daily life to make a difference?
What do you yearn for?
You are invited...
to share experiences develop relationships
explore ways to support one another free lunch! (donations welcome)
Attend this conversation on Saturday, January 10, 10:00-1:00:
Groups from congregations are encouraged to attend together.
RSVP: iowaepiscopal.org or 515-277-6165
Hosted by the Ministry of All the Baptized Core Team: Bishop Alan Scarfe, Julianne Allaway, Kay Beach, Ellen Bruckner, Lydia Bucklin, Steve Godfrey, John Greve, Ronda Haas, John Harper, Lacey Howard, Jean Howe, Aaron Hudson, Georgia Humphrey, Kris Leaman, Torey Lightcap, Lauren Lyon, Jennie McKinney, Kathleen Milligan, Mary Jane Oakland, Elizabeth Popplewell, Ruth Ratliff, Heidi Schleicher, Anne Williams
Episcopal Diocese of Iowa | 225 37th Street | Des Moines, IA 50312
Sunday Afternoon Recital Series
Check out this year's awesome recital concerts! Plan to attend!


text:
Westgate Mfg. WE-119 20W 12V Cast Aluminum Canterbury Long Stem Path Light - Black
Brand: Westgate Mfg. Model: WE-119 Condition: New
Ask a Question
About this Product
Earn 1 Westside Dollar for every 1 piece purchased.
| The Westgate Mfg. 20W 12V Cast Aluminum Canterbury Long Stem Path Light - Black (WE119) presents a great floral design to blend in with your outdoor landscape lighting; matched along with a powerful 12V Low Voltage JC Bi-Pin lamp (Not Included) that can be used up to a 35W max. The Canterbury in particular symbolizes kindness, gratitude and appreciation and are great for landscaping because they put light on the ground where its needed. The Canterbury Long Stem is made of a sturdy, solid cast aluminum body that is built to last under extreme weather conditions for many years. The WE119 comes with 3 ft of cable and a non-metallic spike for grounding. Westgate Landscaping provides a wide selection of directional lights, well lights, area lights, path lights, step lights, underwater lights, and flexible lights that makes any landscape design a convenient process.
|Features:• Easy to install
| Specifications:• Operating Voltage: 12V/20W
• Material: Cast Aluminum
• Lamp Holder: G4
• Lamp Type: JC Bi-Pin, 20W (Not Included)
• Finish: Black
• Accessories: 3 ft cable & non-metallic spike
• Body Length: 26"
• Lamp Diameter: 4-1/2"
Customer Reviews
There are no reviews for this product yet. Be the first to review the product!
Write Your Own Review:
Questions & Answers
Please login or register before adding a question.
If you are a new customer, please register first:
You may also be interested in the following products:
Malibu Lighting 8518-0104-08
Malibu Lighting LED Solar Spot Lights - Brushed Nickel (8 Pack)
Regular Price: $94.99
On Sale: $65.09
Malibu Lighting 8608-0504-01
Malibu Lighting 18W Low Voltage Proscapes Industrial Pivot Path Light - Aged Brass
Regular Price: $34.99
On Sale: $24.06
Malibu Lighting 8421-2200-01
Malibu Lighting 3W Low Voltage 3-Tier LED Path Light - Real Copper
Regular Price: $93.99
On Sale: $64.80
Malibu Lighting 8608-0101-01
Malibu Lighting 20W Low Voltage 2-Tier Industrial Path Light - Aged Brass
Regular Price: $51.99
On Sale: $35.79
Westgate Mfg. WE-148
Westgate Mfg. 20W 12V Cast Aluminum China Hat Path Light - Black
Regular Price: $25.99
On Sale: $17.45


text:
Ski Boot
Sheila GibneyDecember 13, 2000
Does anybody have a receipt for a drink called "Ski Boot". It is made with hot chocolate and alcohol.
* 1 cup Hot chocolate
Could it have been Skier's Toddy (from webtender.com)?
Skier's Toddy
* 1 cup Hot chocolate
* 1 oz Kahlua
* 1 oz Triple sec
* Marshmallows
Mixing instructions:
Rinse out a large mug with boiling water, add steaming hot chocolate, and stir in liqueurs. Top with several marshmallows.
Creator/contributor's comments:
Tia Maria or Creme de Cacao may be used in place of the Kahlua.