http://informahealthcare.com/cot ISSN: 1556-9527 (print), 1556-9535 (electronic) Cutan Ocul Toxicol, Early Online: 1–4 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/15569527.2014.903572
RESEARCH ARTICLE
Effect of intracameral carbachol in phacoemulsification surgery on macular morphology and retinal vessel caliber
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 10/02/14 For personal use only.
Go¨khan Pekel1, Ramazan Yagci1, Semra Acer1, Ebru Nevin Cetin1, Ali Cevik2, and Alper Kasikci1 1
Department of Ophthalmology, Pamukkale University, Camlaralti Mahallesi, Denizli, Turkey and 2Department of Ophthalmology, Tatvan State Hospital, Bitlis, Turkey Abstract
Keywords
Objective: To investigate the effects of intracameral carbachol in phacoemulsification surgery on central macular thickness (CMT), total macular volume (TMV) and retinal vessel caliber (RVC). Materials and methods: In this prospective consecutive case series, 82 patients underwent uneventful phacoemulsification and in-the-bag intraocular lens implantation. Unlike patients in the control group (43 eyes), patients in the study group (42 eyes) were injected with intracameral 0.01% carbachol during surgery. Spectral-domain optical coherence tomography (OCT) was used to analyze the parameters of CMT, TMV and RVC. Results: On the first postoperative day, mean CMT and TMV decreased markedly in the carbachol group, though these values did not change significantly in the control group. During follow-up visits, no statistically significant differences between the groups occurred regarding changes in mean CMT (p ¼ 0.25, first day; p ¼ 0.80, first week; p ¼ 0.95, first month). However, change in mean TMV between groups on the first postoperative day was statistically significant (p ¼ 0.01, first day; p ¼ 0.96, first week; p ¼ 0.68, first month). RVC values were similar on the preoperative and postoperative first days in both groups (p40.05). Discussion: Results suggest that the effect of intracameral carbachol on macular OCT is related to pharmacological effects, as well as optic events (e.g. miosis). Conclusion: Intracameral carbachol given during cataract surgery decreases macular thickness and volume in the early postoperative period but does not exert any gross effect on RVC.
Carbachol, intracameral injection, macula, phacoemulsification
Introduction The intracameral injection of various drugs (e.g. miotics, mydriatics, anesthetics and antibiotics) is a common application during phacoemulsification surgery. Though all of these drugs have beneficial effects sufficient to meriting use, they also pose safety problems that should be considered, such as corneal endothelial damage, anterior chamber reactions, intraocular pressure (IOP) rise and macular edema. The cholinomimetic drug carbachol is primarily used during ophthalmic surgery to induce miosis. The intracameral injection of carbachol provides control of IOP in the early postoperative period, helps the centration of the intraocular lens (IOL), aids in assessing whether the pupil is round and regular and prevents the incarceration of the iris at incision sites1–4. Furthermore, reports have shown that intracameral carbachol 0.01% does not cause corneal edema, corneal endothelial cell damage or macular edema1,5,6. Nevertheless, the literature addressing the effects of intracameral carbachol on macular thickness during the
History Received 21 December 2013 Revised 4 March 2014 Accepted 9 March 2014 Published online 22 April 2014
early postoperative period bears a gap. Closing this gap is important, for the effect of intracameral carbachol appears mostly in the early days of the postoperative period. Since central macular thickness (CMT) and total macular volume (TMV) parameters do not always address the same point, we sought to reveal the influence of carbachol on macular volume. Furthermore, since animal studies have shown that carbachol has a dilatation effect on retinal vessels7, we also sought to examine intracameral carbachol’s impact on retinal vasculature. For this study, we hypothesized that using intracameral carbachol is associated with increased early postoperative inflammation3 and decreased IOP1 and that these effects might influence the macula, or that this impact might be due to the possible toxic effects of carbachol on the retina. We therefore aimed to reveal the effects of the frequently used intracameral carbachol on macular morphology and retinal vessels after uneventful phacoemulsification surgery.
Materials and methods Address for correspondence: Dr. Go¨khan Pekel, Assistant Professor, Department of Ophthalmology, Pamukkale University, K|n|kl|, Camlaralti Mahallesi, Denizli 20070, Turkey. E-mail: [email protected]
In this prospective, comparative and consecutive case series, we recruited 82 patients who underwent uneventful phacoemulsification and in-the-bag IOL implantation.
2
G. Pekel et al.
Cutan Ocul Toxicol, Early Online: 1–4
This study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Institutional Ethical Committee.
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 10/02/14 For personal use only.
Study population This study consisted of two groups: the carbachol group and control group. The age range was 34–81 years for the carbachol group and 33–79 years for the control group. The carbachol group received intracameral 0.5 ml 0.01% carbachol solution (Miostat , Alcon Laboratories, Inc., Fort Worth, TX) directly after viscoelastic substance removal, which followed IOL implantation, while the control group did not. Patient selection for carbachol injection was randomized, and carbachol was not used for complication management in these cases. All patients had clinically significant cataract deterioration that affected their visual acuity. In both groups, cataract types and grades were grades 3–4 nuclear, cortical or posterior subcapsular according to Lens Opacities Classification Systems III8. For all patients, exclusion criteria were any history of ocular surgery, eye trauma, uveitis, retinal disorders or glaucoma; systemic disease that could increase the risk for postoperative inflammation (e.g. diabetes mellitus); and abnormal preoperative macular morphology assessed by optical coherence tomography (OCT) or media opacity that could prevent high-quality macular OCT evaluation. Eyes that received intracameral mydriatics (e.g. epinephrine) were excluded, as well as eyes with intraoperative complications (e.g. extended phacoemulsification times, iris trauma and posterior capsule rupture) and postoperative complications (e.g. corneal incision site leakage, significant posterior capsule opacification, fibrin reaction, ocular hypertension and endophthalmitis). Ocular examinations All preoperative examinations were repeated postoperatively at the first day, first week and first month. At each follow-up visit, all patients received an ophthalmic examination consisting of a visual acuity assessment (Snellen chart), biomicroscopy, air-puff tonometer, indirect retinoscopy and macular OCT measurements. Spectral-domain OCT (SD-OCT, Spectralis , Heidelberg, Germany) was used to analyze the parameters of CMT and TMV. In this study, macular thickness signified the vertical distance between the vitreoretinal interface and the outer border of the retinal pigment epithelium; CMT signified the mean thickness of a 1 mm diameter circular area at the center of the fovea; and TMV signified the total volume of a 6-mm diameter circular space at the center of the macula. Retinal vessel caliber (RVC) measurements were taken with the manual caliber provided by the Spectralis software on the macular analysis screen. Only examinations that adequately visualized temporal retinal vessels were included (Figure 1). We selected 42 macular analysis screens eligible for RVC calculations (n ¼ 21 for each group). For RVC analysis, retinal arterioles and venules passing through an area from one-half to one-disc in diameter from the optic disc margin were measured. The mean thickness values of superior and inferior temporal retinal arterioles and venules were calculated for each eye and recorded for analysis.
Figure 1. Temporal retinal arteriol and venule caliber measurements that were performed on the macular analysis screen of SD-OCT.
RVC examinations included both postoperative first day measurements.
preoperative
and
Surgical technique Mydriasis was achieved by using combined phenylephrine 2.5% and tropicamide 1.0% topical drops prior to surgery. All surgeries were performed using a similar technique, a local anesthesia and a 2.8 mm superior clear corneal incision. In both groups, sodium hyaluronate 1.8% was used during capsulorhexis, and the Alcon Infiniti System (Alcon Laboratories Inc.) was used for phacoemulsification. Phacoemulsification time (range: 30–60 s) was similar in all patients, while phacoemulsification power was set to 35–40% for all operations. Sodium hyaluronate 1.6% was injected into the capsular bag before implanting a one-piece foldable hydrophobic acrylic IOL in the bag. After the removal of the viscoelastic substance, the study group received intracameral 0.5 ml 0.01% carbachol solution to induce miosis. Hydration with balanced salt solution was used to close the corneal incisions. For endophthalmitis prophylaxis, all patients received 0.1 ml intracameral cephalosporin solution. A combination of subconjunctival dexamethasone and gentamicin was applied at the end of surgery in all patients. Topical moxifloxacin and prednisolone acetate eye drops were given six times daily for the first week. Prednisolone acetate was then tapered and discontinued at four weeks after the operation. Statistical analysis For statistical analysis, SPSS 17.0 software for Windows (SPSS Inc., Chicago, IL) was used. A paired samples t test was used to compare mean CMT and TMV values before and after surgery within the same groups, while an independent samples t test was used to compare the mean CMT and TMV changes between the two groups throughout the follow-up visits. The Wilcoxon signed-rank test was used to analyze RVC measurements. p Values less than 0.05 were considered to be statistically significant.
Effect of carbachol on macula
DOI: 10.3109/15569527.2014.903572
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 10/02/14 For personal use only.
Results
3
The major finding of this study was that intracameral 0.01% carbachol decreased TMV during the early postoperative period. Since the macular volume parameter includes more retinal area compared to the CMT parameter, the impact of carbachol seems to have a more diffuse pattern. Our results also showed that during the first postoperative week and
month, the influence of carbachol on the macula in the study group was similar to that in the control group. This result suggests that intracameral carbachol does not have a longlasting effect, as already known1–4. CMT and TMV decreased in both groups on the first postoperative day, though this decrease was more prominent in the carbachol group. In their study, Cohen et al.9 suggested that such a result was due to an artifact of retinal imaging through lenticular opacities. Possible explanations of this difference might involve optical factors, since the pupils are smaller in the carbachol group than in the control group on the first postoperative day. By contrast, this difference might also derive from the parasympathomimetic effect of carbachol, which resembles that of a mechanism in IOP reduction (i.e. increased fluid outflow). Macular edema may develop after cataract surgery10–12. Biro et al.13 reported that no significant change in macular thickness values was found on the first postoperative day, though a significant increase of the perifoveal 3.0 mm and 6.0 mm diameter retinal area thickness occurred on days 7, 30 and 60 postoperatively compared to the preoperative values. In our study, CMT and TMV remained stable on first postoperative day and week, yet increased during the first postoperative month in the control group. By contrast to postoperative first day values, the first week’s and month’s CMV and TMV changes were similar in both groups. Perente et al.14 reported that macular thickness and volume were stable on the first postoperative day after uncomplicated phacoemulsification, though these parameters increased with statistical significance during the first postoperative week and month. Our results were generally concordant with those reports, except for the slight difference in the first week’s results in the control group. Since the macula is a major determinant of visual quality, the effects of various intracameral medications on macular thickness as assessed by OCT have become a popular topic in recent years15–17. Demir et al.6 found that intracameral
Table 1. Some of the demographic and clinical characteristics of the patients.
Table 3. Retinal arteriolar and venular caliber measurements (mm) in the study and control groups at preoperation and postoperative first day.
Table 1 shows some demographic and clinical characteristics of the patients. In the carbachol group, preoperative BCVA was 0.55 ± 0.29 logMAR, while postoperative BCVA at the final follow-up visit was 0.01 ± 0.03 logMAR (p50.001). In the control group, preoperative BCVA was 0.46 ± 0.22 logMAR and postoperative BCVA at the final follow-up visit was 0.02 ± 0.04 logMAR (p50.001). Table 2 shows the mean CMT and TMV values of the carbachol group and control group during the follow-up visits. On the first postoperative day, mean CMT and TMV decreased markedly in the carbachol group, though they did not change significantly in the control group. At the postoperative first week and month, mean CMT and TMV showed similar changes in both groups. There were no statistically significant differences between the two groups in the aspect of change in thickness in mean CMT during the follow-up visits (p ¼ 0.25, first day; p ¼ 0.80, first week; p ¼ 0.95, first month). However, change in mean TMV between the groups at the first postoperative day was statistically significant (p ¼ 0.01, first day; p ¼ 0.96, first week; p ¼ 0.68, first month). Table 3 shows RVC measurements. Preoperative and postoperative first day retinal arteriole and venule caliber measurements were similar in both groups. No eye developed cystoid macular edema or clinically significant macular edema, nor in any eye did we encounter bullous keratopathy, postoperative severe ocular hypertension, fibrin reaction or endophthalmitis.
Discussion
Number of patients (eyes) Mean age (years) Gender Operated eyes (R/L)
Carbachol group
Control group
41 (42) 66.9 ± 9.7 22 M, 19 F 20 R, 22 L
41 (43) 64.0 ± 10.1 22 M, 19 F 23 R, 20 L
M: male, F: female, R: right, and L: left.
Carbachol group Preop.
Postop.
RAC 97.1 ± 6.8 98.0 ± 6.2 RVC 131.3 ± 12.0 133.2 ± 11.3
Control group p Value 0.18 0.07
Preop.
Postop.
p Value
95.6 ± 6.7 96.4 ± 7.3 127.0 ± 11.8 127.4 ± 13.6
0.33 0.88
RAC: retinal arteriolar caliber and RVC: retinal venular caliber.
Table 2. The mean central macular thickness and total macular volume of the carbachol group and the control group are shown.
CMT (mm) Carbachol group Control group TMV (mm3) Carbachol group Control group
Pre-op
First day
First week
First month
262.9 ± 20.1 268.7 ± 26.5
257.1 ± 18.3 (p ¼ 0.003) 265.2 ± 26.4 (p ¼ 0.051)
260.8 ± 21.7 (p ¼ 0.28) 270.9 ± 23.3 (p ¼ 0.055)
268.2 ± 24.1 (p ¼ 0.002) 275.2 ± 28.3 (p50.001)
8.39 ± 0.48 8.50 ± 0.50
8.24 ± 0.58 (p ¼ 0.002) 8.47 ± 0.50 (p ¼ 0.94)
8.45 ± 0.56 (p ¼ 0.10) 8.58 ± 0.49 (p ¼ 0.057)
8.54 ± 0.56 (p50.001) 8.70 ± 0.52 (p50.001)
Pre-op: preoperative, CMT: central macular thickness and TMV: total macular volume. p Values are calculated according to the comparison with the baseline preoperative values.
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4
G. Pekel et al.
carbachol given during phacoemulsification had no effect on foveal thickness during the fourth postoperative week. Meanwhile, Solomon et al.18 reported that intraoperative intracameral carbachol had a positive influence on early postoperative visual acuity. Though this result seems due to miosis, changes in macular morphology might be another factor. Azizi et al.19 investigated the effects of phacoemulsification surgery on RVC and found that the retinal arteriolar diameter was reduced following the operation. However, they concluded that the cataractous lens might cause erroneous elevation in RVC measurements taken by laser Doppler flowmetry19. In this study, we used SD-OCT to measure RVC, and we believe that this device provides reliable, reproducible data. We did not find important alterations in RVC measurements after cataract surgery. Though carbachol has a vasodilation effect on retinal vessels7, intracameral use does not significantly influence RVC. Nevertheless, our study has its limitations. First, we did not have the opportunity to measure postoperative inflammation with a laser flare cell meter, which would have provided quantitative and objective data. Second, it was inappropriate to correlate early postoperative macular changes and visual acuity changes between groups, for pupil size differed and thus might have affected clinical relevance. Finally, we injected another intracameral medication (i.e. cephalosporin) after the initial intracameral carbachol injection, since it was reported that intracameral cephalosporins are compatible with carbachol20 and do not change macular thickness after cataract surgery21.
Conclusion Intracameral carbachol given during phacoemulsification surgery decreases TMV and CMT during the early postoperative period. In this study, however, only TMV change was markedly different between groups. Both phacoemulsification and carbachol use do not have significant impact on RVC measurements on the first postoperative day. We believe that further studies of the effects of different doses of intracameral carbachol and the influence of carbachol in ruptured posterior capsule cases might provide a better understanding of the impact of carbachol on macula.
Declaration of interest The authors state no conflict of interest.
References 1. Cekic¸ O, Batman C. Effect of intracameral carbachol on intraocular pressure following clear corneal phacoemulsification. Eye 1999;13:209–211.
Cutan Ocul Toxicol, Early Online: 1–4
2. Ruiz RS, Rhem MN, Prager TC. Effects of carbachol and acetylcholine on intraocular pressure after cataract extraction. Am J Ophthalmol 1989;107:7–10. 3. Roberts CW. Intraocular miotics and postoperative inflammation. J Cataract Refract Surg 1993;19:731–734. 4. McKinzie JW, Boggs Jr MB. Comparison of postoperative intraocular pressure after use of Miochol and Miostat. J Cataract Refract Surg 1989;15:185–190. 5. Liou SW, Chiu CJ, Wang IJ. Effect of intracameral injection of lidocaine and carbachol on the rabbit corneal endothelium. J Cataract Refract Surg 2004;30:1351–1355. 6. Demir M, Oba E, Dirim B, et al. Effect of intracameral carbachol given during cataract surgery on macular thickness. Int Ophthalmol 2012;32:413–416. 7. Gericke A, Sniatecki JJ, Goloborodko E, et al. Identification of the muscarinic acetylcholine receptor subtype mediating cholinergic vasodilation in murine retinal arterioles. Invest Ophthalmol Vis Sci 2011;52:7479–7484. 8. Chylack Jr LT, Wolfe JK, Singer DM, et al. The lens opacities classification system III; the longitudinal study of cataract study group. Arch Ophthalmol 1993;111:831–836. 9. Cohen KL, Patel SB, Ray N. Retinal thickness measurement after phacoemulsification. J Cataract Refract Surg 2004;30:1501–1506; errata 2005;31:14. 10. Kim SJ, Belair ML, Bressler NM, et al. A method of reporting macular edema after cataract surgery using optical coherence tomography. Retina 2008;28:870–876. 11. Cagini C, Fiore T, Iaccheri B, et al. Macular thickness measured by optical coherence tomography in a healthy population before and after uncomplicated cataract phacoemulsification surgery. Curr Eye Res 2009;34:1036–1041. 12. Georgopoulos GT, Papaconstantinou D, Niskopoulou M, et al. Foveal thickness after phacoemulsification as measured by optical coherence tomography. Clin Ophthalmol 2008;2:817–820. 13. Biro Z, Balla Z, Kovacs B. Change of foveal and perifoveal thickness measured by OCT after phacoemulsification and IOL implantation. Eye 2008;22:8–12. 14. Perente I, Utine CA, Ozturker C, et al. Evaluation of macular changes after uncomplicated phacoemulsification surgery by optical coherence tomography. Curr Eye Res 2007; 32:241–247. 15. Bozkurt E, Yazici AT, Pekel G, et al. Effect of intracameral epinephrine use on macular thickness after uneventful phacoemulsification. J Cataract Refract Surg 2010;36:1380–1384. 16. Lam PT, Young AL, Cheng LL, et al. Randomized controlled trial on the safety of intracameral cephalosporins in cataract surgery. Clin Ophthalmol 2010;4:1499–1504. 17. Johansson M, Lundberg B, Behndig A. Optical coherence tomography evaluation of macular edema after phacoemulsification surgery with intracameral mydriatics. J Cataract Refract Surg 2007;33:1436–1441. 18. Solomon KD, Stewart WC, Hunt HH, et al. Intraoperative intracameral carbachol in phacoemulsification and posterior chamber lens implantation. Am J Ophthalmol 1998;125:36–43. 19. Azizi B, Wong T, Wan J, et al. The impact of cataract on the quantitative, non-invasive assessment of retinal blood flow. Acta Ophthalmol 2012;90:9–12. 20. Hui M, Lam PT, Cheung SW, et al. In vitro compatibility study of cephalosporin with intraocular irrigating solutions and intracameral medications. Clin Experiment Ophthalmol 2011;39: 164–170. 21. Gupta MS, McKee HD, Saldan˜a M, Stewart OG. Macular thickness after cataract surgery with intracameral cefuroxime. J Cataract Refract Surg 2005;31:1163–1166.
RESEARCH ARTICLE
Effect of intracameral carbachol in phacoemulsification surgery on macular morphology and retinal vessel caliber
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 10/02/14 For personal use only.
Go¨khan Pekel1, Ramazan Yagci1, Semra Acer1, Ebru Nevin Cetin1, Ali Cevik2, and Alper Kasikci1 1
Department of Ophthalmology, Pamukkale University, Camlaralti Mahallesi, Denizli, Turkey and 2Department of Ophthalmology, Tatvan State Hospital, Bitlis, Turkey Abstract
Keywords
Objective: To investigate the effects of intracameral carbachol in phacoemulsification surgery on central macular thickness (CMT), total macular volume (TMV) and retinal vessel caliber (RVC). Materials and methods: In this prospective consecutive case series, 82 patients underwent uneventful phacoemulsification and in-the-bag intraocular lens implantation. Unlike patients in the control group (43 eyes), patients in the study group (42 eyes) were injected with intracameral 0.01% carbachol during surgery. Spectral-domain optical coherence tomography (OCT) was used to analyze the parameters of CMT, TMV and RVC. Results: On the first postoperative day, mean CMT and TMV decreased markedly in the carbachol group, though these values did not change significantly in the control group. During follow-up visits, no statistically significant differences between the groups occurred regarding changes in mean CMT (p ¼ 0.25, first day; p ¼ 0.80, first week; p ¼ 0.95, first month). However, change in mean TMV between groups on the first postoperative day was statistically significant (p ¼ 0.01, first day; p ¼ 0.96, first week; p ¼ 0.68, first month). RVC values were similar on the preoperative and postoperative first days in both groups (p40.05). Discussion: Results suggest that the effect of intracameral carbachol on macular OCT is related to pharmacological effects, as well as optic events (e.g. miosis). Conclusion: Intracameral carbachol given during cataract surgery decreases macular thickness and volume in the early postoperative period but does not exert any gross effect on RVC.
Carbachol, intracameral injection, macula, phacoemulsification
Introduction The intracameral injection of various drugs (e.g. miotics, mydriatics, anesthetics and antibiotics) is a common application during phacoemulsification surgery. Though all of these drugs have beneficial effects sufficient to meriting use, they also pose safety problems that should be considered, such as corneal endothelial damage, anterior chamber reactions, intraocular pressure (IOP) rise and macular edema. The cholinomimetic drug carbachol is primarily used during ophthalmic surgery to induce miosis. The intracameral injection of carbachol provides control of IOP in the early postoperative period, helps the centration of the intraocular lens (IOL), aids in assessing whether the pupil is round and regular and prevents the incarceration of the iris at incision sites1–4. Furthermore, reports have shown that intracameral carbachol 0.01% does not cause corneal edema, corneal endothelial cell damage or macular edema1,5,6. Nevertheless, the literature addressing the effects of intracameral carbachol on macular thickness during the
History Received 21 December 2013 Revised 4 March 2014 Accepted 9 March 2014 Published online 22 April 2014
early postoperative period bears a gap. Closing this gap is important, for the effect of intracameral carbachol appears mostly in the early days of the postoperative period. Since central macular thickness (CMT) and total macular volume (TMV) parameters do not always address the same point, we sought to reveal the influence of carbachol on macular volume. Furthermore, since animal studies have shown that carbachol has a dilatation effect on retinal vessels7, we also sought to examine intracameral carbachol’s impact on retinal vasculature. For this study, we hypothesized that using intracameral carbachol is associated with increased early postoperative inflammation3 and decreased IOP1 and that these effects might influence the macula, or that this impact might be due to the possible toxic effects of carbachol on the retina. We therefore aimed to reveal the effects of the frequently used intracameral carbachol on macular morphology and retinal vessels after uneventful phacoemulsification surgery.
Materials and methods Address for correspondence: Dr. Go¨khan Pekel, Assistant Professor, Department of Ophthalmology, Pamukkale University, K|n|kl|, Camlaralti Mahallesi, Denizli 20070, Turkey. E-mail: [email protected]
In this prospective, comparative and consecutive case series, we recruited 82 patients who underwent uneventful phacoemulsification and in-the-bag IOL implantation.
2
G. Pekel et al.
Cutan Ocul Toxicol, Early Online: 1–4
This study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Institutional Ethical Committee.
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 10/02/14 For personal use only.
Study population This study consisted of two groups: the carbachol group and control group. The age range was 34–81 years for the carbachol group and 33–79 years for the control group. The carbachol group received intracameral 0.5 ml 0.01% carbachol solution (Miostat , Alcon Laboratories, Inc., Fort Worth, TX) directly after viscoelastic substance removal, which followed IOL implantation, while the control group did not. Patient selection for carbachol injection was randomized, and carbachol was not used for complication management in these cases. All patients had clinically significant cataract deterioration that affected their visual acuity. In both groups, cataract types and grades were grades 3–4 nuclear, cortical or posterior subcapsular according to Lens Opacities Classification Systems III8. For all patients, exclusion criteria were any history of ocular surgery, eye trauma, uveitis, retinal disorders or glaucoma; systemic disease that could increase the risk for postoperative inflammation (e.g. diabetes mellitus); and abnormal preoperative macular morphology assessed by optical coherence tomography (OCT) or media opacity that could prevent high-quality macular OCT evaluation. Eyes that received intracameral mydriatics (e.g. epinephrine) were excluded, as well as eyes with intraoperative complications (e.g. extended phacoemulsification times, iris trauma and posterior capsule rupture) and postoperative complications (e.g. corneal incision site leakage, significant posterior capsule opacification, fibrin reaction, ocular hypertension and endophthalmitis). Ocular examinations All preoperative examinations were repeated postoperatively at the first day, first week and first month. At each follow-up visit, all patients received an ophthalmic examination consisting of a visual acuity assessment (Snellen chart), biomicroscopy, air-puff tonometer, indirect retinoscopy and macular OCT measurements. Spectral-domain OCT (SD-OCT, Spectralis , Heidelberg, Germany) was used to analyze the parameters of CMT and TMV. In this study, macular thickness signified the vertical distance between the vitreoretinal interface and the outer border of the retinal pigment epithelium; CMT signified the mean thickness of a 1 mm diameter circular area at the center of the fovea; and TMV signified the total volume of a 6-mm diameter circular space at the center of the macula. Retinal vessel caliber (RVC) measurements were taken with the manual caliber provided by the Spectralis software on the macular analysis screen. Only examinations that adequately visualized temporal retinal vessels were included (Figure 1). We selected 42 macular analysis screens eligible for RVC calculations (n ¼ 21 for each group). For RVC analysis, retinal arterioles and venules passing through an area from one-half to one-disc in diameter from the optic disc margin were measured. The mean thickness values of superior and inferior temporal retinal arterioles and venules were calculated for each eye and recorded for analysis.
Figure 1. Temporal retinal arteriol and venule caliber measurements that were performed on the macular analysis screen of SD-OCT.
RVC examinations included both postoperative first day measurements.
preoperative
and
Surgical technique Mydriasis was achieved by using combined phenylephrine 2.5% and tropicamide 1.0% topical drops prior to surgery. All surgeries were performed using a similar technique, a local anesthesia and a 2.8 mm superior clear corneal incision. In both groups, sodium hyaluronate 1.8% was used during capsulorhexis, and the Alcon Infiniti System (Alcon Laboratories Inc.) was used for phacoemulsification. Phacoemulsification time (range: 30–60 s) was similar in all patients, while phacoemulsification power was set to 35–40% for all operations. Sodium hyaluronate 1.6% was injected into the capsular bag before implanting a one-piece foldable hydrophobic acrylic IOL in the bag. After the removal of the viscoelastic substance, the study group received intracameral 0.5 ml 0.01% carbachol solution to induce miosis. Hydration with balanced salt solution was used to close the corneal incisions. For endophthalmitis prophylaxis, all patients received 0.1 ml intracameral cephalosporin solution. A combination of subconjunctival dexamethasone and gentamicin was applied at the end of surgery in all patients. Topical moxifloxacin and prednisolone acetate eye drops were given six times daily for the first week. Prednisolone acetate was then tapered and discontinued at four weeks after the operation. Statistical analysis For statistical analysis, SPSS 17.0 software for Windows (SPSS Inc., Chicago, IL) was used. A paired samples t test was used to compare mean CMT and TMV values before and after surgery within the same groups, while an independent samples t test was used to compare the mean CMT and TMV changes between the two groups throughout the follow-up visits. The Wilcoxon signed-rank test was used to analyze RVC measurements. p Values less than 0.05 were considered to be statistically significant.
Effect of carbachol on macula
DOI: 10.3109/15569527.2014.903572
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 10/02/14 For personal use only.
Results
3
The major finding of this study was that intracameral 0.01% carbachol decreased TMV during the early postoperative period. Since the macular volume parameter includes more retinal area compared to the CMT parameter, the impact of carbachol seems to have a more diffuse pattern. Our results also showed that during the first postoperative week and
month, the influence of carbachol on the macula in the study group was similar to that in the control group. This result suggests that intracameral carbachol does not have a longlasting effect, as already known1–4. CMT and TMV decreased in both groups on the first postoperative day, though this decrease was more prominent in the carbachol group. In their study, Cohen et al.9 suggested that such a result was due to an artifact of retinal imaging through lenticular opacities. Possible explanations of this difference might involve optical factors, since the pupils are smaller in the carbachol group than in the control group on the first postoperative day. By contrast, this difference might also derive from the parasympathomimetic effect of carbachol, which resembles that of a mechanism in IOP reduction (i.e. increased fluid outflow). Macular edema may develop after cataract surgery10–12. Biro et al.13 reported that no significant change in macular thickness values was found on the first postoperative day, though a significant increase of the perifoveal 3.0 mm and 6.0 mm diameter retinal area thickness occurred on days 7, 30 and 60 postoperatively compared to the preoperative values. In our study, CMT and TMV remained stable on first postoperative day and week, yet increased during the first postoperative month in the control group. By contrast to postoperative first day values, the first week’s and month’s CMV and TMV changes were similar in both groups. Perente et al.14 reported that macular thickness and volume were stable on the first postoperative day after uncomplicated phacoemulsification, though these parameters increased with statistical significance during the first postoperative week and month. Our results were generally concordant with those reports, except for the slight difference in the first week’s results in the control group. Since the macula is a major determinant of visual quality, the effects of various intracameral medications on macular thickness as assessed by OCT have become a popular topic in recent years15–17. Demir et al.6 found that intracameral
Table 1. Some of the demographic and clinical characteristics of the patients.
Table 3. Retinal arteriolar and venular caliber measurements (mm) in the study and control groups at preoperation and postoperative first day.
Table 1 shows some demographic and clinical characteristics of the patients. In the carbachol group, preoperative BCVA was 0.55 ± 0.29 logMAR, while postoperative BCVA at the final follow-up visit was 0.01 ± 0.03 logMAR (p50.001). In the control group, preoperative BCVA was 0.46 ± 0.22 logMAR and postoperative BCVA at the final follow-up visit was 0.02 ± 0.04 logMAR (p50.001). Table 2 shows the mean CMT and TMV values of the carbachol group and control group during the follow-up visits. On the first postoperative day, mean CMT and TMV decreased markedly in the carbachol group, though they did not change significantly in the control group. At the postoperative first week and month, mean CMT and TMV showed similar changes in both groups. There were no statistically significant differences between the two groups in the aspect of change in thickness in mean CMT during the follow-up visits (p ¼ 0.25, first day; p ¼ 0.80, first week; p ¼ 0.95, first month). However, change in mean TMV between the groups at the first postoperative day was statistically significant (p ¼ 0.01, first day; p ¼ 0.96, first week; p ¼ 0.68, first month). Table 3 shows RVC measurements. Preoperative and postoperative first day retinal arteriole and venule caliber measurements were similar in both groups. No eye developed cystoid macular edema or clinically significant macular edema, nor in any eye did we encounter bullous keratopathy, postoperative severe ocular hypertension, fibrin reaction or endophthalmitis.
Discussion
Number of patients (eyes) Mean age (years) Gender Operated eyes (R/L)
Carbachol group
Control group
41 (42) 66.9 ± 9.7 22 M, 19 F 20 R, 22 L
41 (43) 64.0 ± 10.1 22 M, 19 F 23 R, 20 L
M: male, F: female, R: right, and L: left.
Carbachol group Preop.
Postop.
RAC 97.1 ± 6.8 98.0 ± 6.2 RVC 131.3 ± 12.0 133.2 ± 11.3
Control group p Value 0.18 0.07
Preop.
Postop.
p Value
95.6 ± 6.7 96.4 ± 7.3 127.0 ± 11.8 127.4 ± 13.6
0.33 0.88
RAC: retinal arteriolar caliber and RVC: retinal venular caliber.
Table 2. The mean central macular thickness and total macular volume of the carbachol group and the control group are shown.
CMT (mm) Carbachol group Control group TMV (mm3) Carbachol group Control group
Pre-op
First day
First week
First month
262.9 ± 20.1 268.7 ± 26.5
257.1 ± 18.3 (p ¼ 0.003) 265.2 ± 26.4 (p ¼ 0.051)
260.8 ± 21.7 (p ¼ 0.28) 270.9 ± 23.3 (p ¼ 0.055)
268.2 ± 24.1 (p ¼ 0.002) 275.2 ± 28.3 (p50.001)
8.39 ± 0.48 8.50 ± 0.50
8.24 ± 0.58 (p ¼ 0.002) 8.47 ± 0.50 (p ¼ 0.94)
8.45 ± 0.56 (p ¼ 0.10) 8.58 ± 0.49 (p ¼ 0.057)
8.54 ± 0.56 (p50.001) 8.70 ± 0.52 (p50.001)
Pre-op: preoperative, CMT: central macular thickness and TMV: total macular volume. p Values are calculated according to the comparison with the baseline preoperative values.
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G. Pekel et al.
carbachol given during phacoemulsification had no effect on foveal thickness during the fourth postoperative week. Meanwhile, Solomon et al.18 reported that intraoperative intracameral carbachol had a positive influence on early postoperative visual acuity. Though this result seems due to miosis, changes in macular morphology might be another factor. Azizi et al.19 investigated the effects of phacoemulsification surgery on RVC and found that the retinal arteriolar diameter was reduced following the operation. However, they concluded that the cataractous lens might cause erroneous elevation in RVC measurements taken by laser Doppler flowmetry19. In this study, we used SD-OCT to measure RVC, and we believe that this device provides reliable, reproducible data. We did not find important alterations in RVC measurements after cataract surgery. Though carbachol has a vasodilation effect on retinal vessels7, intracameral use does not significantly influence RVC. Nevertheless, our study has its limitations. First, we did not have the opportunity to measure postoperative inflammation with a laser flare cell meter, which would have provided quantitative and objective data. Second, it was inappropriate to correlate early postoperative macular changes and visual acuity changes between groups, for pupil size differed and thus might have affected clinical relevance. Finally, we injected another intracameral medication (i.e. cephalosporin) after the initial intracameral carbachol injection, since it was reported that intracameral cephalosporins are compatible with carbachol20 and do not change macular thickness after cataract surgery21.
Conclusion Intracameral carbachol given during phacoemulsification surgery decreases TMV and CMT during the early postoperative period. In this study, however, only TMV change was markedly different between groups. Both phacoemulsification and carbachol use do not have significant impact on RVC measurements on the first postoperative day. We believe that further studies of the effects of different doses of intracameral carbachol and the influence of carbachol in ruptured posterior capsule cases might provide a better understanding of the impact of carbachol on macula.
Declaration of interest The authors state no conflict of interest.
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