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ARTICLE Changes in central corneal thickness after congenital cataract surgery Amir Faramarzi, MD, Mohammad Ali Javadi, MD, Mohammad Hossein Jabbarpoor Bonyadi, MD, Mehdi Yaseri, MS PURPOSE: To evaluate central corneal thickness (CCT) changes after congenital cataract surgery with or without intraocular lens (IOL) implantation. SETTING: Ophthalmic Research Center, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. DESIGN: Comparative case series. METHODS: Anterior lensectomy and anterior vitrectomy were performed in eyes with congenital cataract. Eyes had IOL implantation (pseudophakic group) or remained aphakic (aphakic group). The CCT and intraocular pressure were measured in all cases preoperatively and 1 and 6 months postoperatively. Age-matched normal eyes served as a control group. RESULTS: The study evaluated 47 eyes (30 patients), 32 pseudophakic and 15 aphakic. The mean preoperative CCT was 540 mm G 34 (SD) in the pseudophakic group, 548 G 61 mm in the aphakic group, and 558 G 36 mm in the control group (P Z .207). The mean CCT in the aphakic group was significantly greater than in the pseudophakic group (587 G 65 mm versus 539 G 37 mm) 1 month postoperatively (P Z .018) and at 6 months (602 G 65 mm versus 540 G 36 mm) (P Z .012). Although the CCT values in the pseudophakic group at 1 month and 6 months were similar to preoperative values (P Z .463 and P Z 1.00, respectively), both postoperative CCT values in the aphakic group were significantly greater than preoperatively (P<.001). CONCLUSIONS: The CCT in eyes with congenital cataract was similar to that in normal age-matched eyes. However, shortly after cataract removal, the CCT was significantly greater in aphakic eyes than in pseudophakic eyes. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2010; 36:2041–2047 Q 2010 ASCRS and ESCRS Increased central corneal thickness (CCT) after removal of a congenital cataract has been reported.1–5 It is unclear whether the increased CCT is present before surgery or develops postoperatively. Most investigators believe the change occurs postoperatively.1,4 Some suggest that surgical trauma at the time of cataract extraction may compromise endothelial cell function and result in increased CCT in these patients.3,5 In adults6–9 and in children,10 a thicker central cornea is associated with higher intraocular pressure (IOP) readings by Goldmann applanation tonometry. The thickened cornea after congenital cataract extraction can lead to overestimation of IOP readings and cause over diagnosis of aphakic glaucoma with overuse of antiglaucoma medications. In this study, we sought to answer 2 questions: (1) Is the CCT increased in eyes with congenital cataract Q 2010 ASCRS and ESCRS Published by Elsevier Inc. compared with that in normal eyes? (2) Does cataract extraction (with or without intraocular lens [IOL] implantation) have an effect on CCT? To answer these questions, we measured the CCT in eyes with congenital cataract preoperatively and compared the results with those in normal age-matched eyes. We continued to measure the CCT for 6 months after cataract surgery in aphakic eyes and pseudophakic eyes. To our knowledge, this is the first longitudinal study to analyze CCT before and after congenital cataract extraction and to evaluate the role of IOL implantation on CCT in pediatric cataract surgery. PATIENTS AND METHODS All congenital cataract cases consecutively scheduled for surgery at Labbafinejad Medical Center between January 2008 and September 2009 were enrolled in this prospective study. 0886-3350/$ - see front matter doi:10.1016/j.jcrs.2010.07.016 2041 2042 CCT CHANGES AFTER CONGENITAL CATARACT SURGERY Normal eyes of children who had general anesthesia for urological procedures at the same center were recruited as a control group. An institutional review board reviewed and approved the study protocol. Inclusion criteria were congenital or developmental cataract severe enough to decrease the red reflex to less than three tenths and significant blocking of the visual axis. Exclusion criteria were ocular pathology other than congenital cataract, including traumatic cataract, pathologic cataract, microphthalmos, glaucoma, corneal opacity, anterior segment dysgenesis, iris coloboma, and accompanying uveitis. All patients had a detailed preoperative evaluation. Visual acuity was assessed using Snellen charts when possible; if not, fixation patterns were noted. The red reflex was evaluated by direct ophthalmoscopy. Slitlamp biomicroscopy evaluation of the anterior segment was performed preoperatively in cooperative patients. A retinal examination was performed by indirect ophthalmoscopy. If media opacity was so severe that the retina could not be seen, B-scan ultrasonography was performed. Infants who could not cooperate for examination were scheduled for examination under general anesthesia. During general anesthesia, detailed ophthalmic evaluation was done, including IOP measurement with a Tono-Pen (Reichert). Tonometry was performed no longer than 5 minutes after induction of anesthesia. The CCT was measured with an ultrasonic pachymeter (Pachymeter SP-2000, Tomey Corp.) soon after induction of anesthesia. The pachymeter probe was placed lightly on the center of the cornea 3 times. At each contact, the CCT was measured 10 times automatically (auto mode). The instrument automatically calculated the mean measurement. During the procedure, the cornea was moistened frequently with a balanced salt solution to ensure it was adequately hydrated. The same examiner (A.F.) performed all CCT measurements. Based on the findings of the examination under general anesthesia, if cataract extraction was indicated, patients had surgery at the same session. The IOL power was calculated using the SRK/T formula based on the keratometry (K) reading and axial length. When keratometry could not be performed, the standard K reading for the patient’s age was used.11 To prevent a postoperative myopic shift, a 10% reduction in IOL power was considered for children younger than 5 years. A 3-piece foldable acrylic posterior chamber IOL with poly(methyl methacrylate) haptics (AcrySof Submitted: April 27, 2010. Final revision submitted: July 6, 2010. Accepted: July 10, 2010. From the Ophthalmic Research Center (Faramarzi, Javadi, Bonyadi), Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, and the Department of Epidemiology and Biostatics (Yaseri), School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. MA60BM, Alcon, Inc.) was implanted in pseudophakic eyes. If the patient had bilateral cataract and was younger than 6 months, an IOL was not implanted. In cases of unilateral cataract, an IOL was implanted in infants older than 2 months. In these cases, the nonoperated fellow eye was considered a control for the operated eye. Bilateral cases did not have simultaneous surgery; the second eye was operated on no more than 1 month after the first eye. Surgical Technique The same experienced surgeon (A.F.) performed all procedures using general anesthesia. Preoperative pupil dilation was achieved by tropicamide 1% eyedrops. After the necessary limbal incisions were made and the anterior chamber was deepened with hydroxypropyl methylcellulose 2%, a forceps-assisted anterior capsulorhexis was created. Adequate hydrodissection and manual lens aspiration with a Simcoe irrigation/aspiration system were performed. A posterior continuous curvilinear capsulorhexis was initiated with a 27-gauge cystotome and completed with a capsulorhexis forceps. A 2-port central anterior vitrectomy was performed through 2 limbal paracenteses. Machine parameters included a cut rate of 600 cuts/min and vacuum of 100 mm Hg. If the eye was a candidate for IOL implantation, the IOL was placed in the ciliary sulcus. Then, the optic was captured through the posterior capsulorhexis with a second instrument (sealed-bag technique12). After meticulous irrigation of the anterior chamber, the incisions were closed with 10-0 nylon. At the end of surgery, all eyes received a subconjunctival injection of 100 mg of cephazolin, 2 mg of dexamethasone, and a sub-Tenon injection of 20 mg methylprednisolone acetate. Postoperative Treatment Postoperative treatment included betamethasone eyedrops 6 times a day, tapered over 6 weeks, and chloramphenicol eyedrops 4 times a day for 1 week. Postoperative dilation was achieved intermittently using tropicamide 1% to prevent synechiae formation. Patients were examined postoperatively at 1 and 2 days, 1 and 2 weeks, and 1, 3, and 6 months. Each visit included visual acuity, slitlamp biomicroscopy evaluation, and IOP measurement with a TonoPen when possible. One month and 6 months after surgery, the CCT was measured. In patients unable to cooperate, the measurement was performed using general anesthesia; the evaluation also included a detailed ophthalmic examination including refraction, suture removal, and IOP measurement with a Tono-Pen. The method of CCT measurement was the same as the technique used before surgery. Statistical Analysis Supported by the Ophthalmic Research Center, Shahid Beheshti Medical University, Tehran, Iran. Descriptive statistical results are presented as the mean, standard deviation, and minimum and maximum values. Paired t tests were used to analyze the differences between each pair of measurements. A P value less than 0.05 was considered statistically significant. Corresponding author: Amir Faramarzi, MD, Ophthalmic Research Center, Labbafinejad Medical Center, Pasdaran Avenue Boostan 9 Street, Tehran 1666694516, Iran E-mail: amirfaramarzy@yahoo. com. RESULTS The study enrolled 47 eyes of 30 patients; 19 patients (63.3%) were boys. Seventeen patients had bilateral J CATARACT REFRACT SURG - VOL 36, DECEMBER 2010 2043 CCT CHANGES AFTER CONGENITAL CATARACT SURGERY Table 1. Baseline descriptive statistics by group. Group Variable Pseudophakic (n Z 32) Aphakic (n Z 15) Control (n Z 51) 37.7 G 26.9 2–102 16/16 11/10 540 G 34 5.6 G 6.1 1–28 8/7 6/3 548 G 61 29.1 G 25.6 1–96 26/25 25/1 558 G 36 P Value !.001 Age (mo) Mean G SD Range Right eye/left eye (n) Bilateral/monolateral (n) Mean CCT (mm) G SD O.999 d .207 CCT Z central corneal thickness congenital cataract; in these cases, both eyes were entered in the study. Table 1 shows baseline characteristics of 32 pseudophakic eyes of 21 patients, 15 aphakic eyes of 9 patients, and 51 normal eyes of 26 patients (control group). There was no significant difference in the mean baseline CCT between the 3 groups (P Z .207). Table 2 shows the preoperative and postoperative mean CCT values in the aphakic group and pseudophakic group and the statistical analysis results in each group and between the pseudophakic group and the aphakic group. The difference between the 2 groups in the mean CCT at the 1-month follow-up visit was statistically significant (P Z .018). This difference was greater after adjustment of the 1-month CCT values for baseline CCT values (P!.001). The difference between the 2 groups at 6 months was also statistically significant (P Z .012) (Figures 1 and 2). This difference was greater after adjustment of the 6-month CCT values for baseline CCT values (P!.001). After the 2 groups were adjusted for age and preoperative CCT values, the differences remained significant at 1 month and 6 months (P!.001) (Table 2). In the pseudophakic group, there was no significant difference between the 1-month and 6-month postoperative CCT values and the baseline measurements (P Z .463 and P Z 1.00, respectively). In the aphakic group, however, both differences were statistically significant (P!.001) (Table 2). Table 3 shows baseline and follow-up data comparing the 10 unilateral pseudophakic eyes and the nonoperated fellow eyes (controls). There was no significant difference in the mean CCT measurements between the 2 subgroups at any time. The mean preoperative IOP was 15 G 5.6 mm Hg in the pseudophakic group and 14.1 G 4.6 mm Hg in the aphakic group (P Z .51). The mean IOP 6 months postoperatively was 14.5 G 4.2 mm Hg and 15.2 G 3.3 mm Hg, respectively (P Z .39). There was no significant Table 2. Preoperative and postoperative mean CCT values in the aphakic group and pseudophakic group and statistical analysis results in each group and between the 2 groups. Mean (mm) G SD Time Baseline Postoperative 1 Month CCT Change P value, within* 6 Months CCT Change P value, within* P Value Pseudophakic Group (n Z 32) Aphakic Group (n Z 15) Mean Difference (95% CI) 540 G 34 548 G 61 8 ( 36 to 19) .831 539 G 37 2 G 17 .463 587 G 65 38 G 30 !.001 48 ( 78 to 18) 36 (21 to 52) d .018 !.001 d !.001 d d 540 G 36 0 G 18 1.0 602 G 65 50 G 31 !.001 62 ( 92 to 33) 7 (4 to 10) d .012 !.001 d !.001 d d CI Z confidence interval; CCT Z central corneal thickness; GEE Z generalized estimating equation *Based on paired t test † Adjusted for baseline values and age (based on GEE) J CATARACT REFRACT SURG - VOL 36, DECEMBER 2010 Based on GEE Adjusted† d 2044 CCT CHANGES AFTER CONGENITAL CATARACT SURGERY Figure 1. Mean and 95% CI of CCT in aphakic eyes and pseudophakic eyes at baseline and postoperatively at 1 month and 6 months (CCT Z central corneal thickness; CI Z confidence interval). Figure 2. Mean and 95% CI of CCT changes in aphakic eyes and pseudophakic eyes at baseline and postoperatively at 1 month and 6 months (CCT Z central corneal thickness; CI Z confidence interval). difference in the mean preoperative or 6-month postoperative IOP within the aphakic group or within the pseudophakic group (P Z .58 and P Z .74, respectively). There were no significant intraoperative complications. During short-term follow-up, there were 3 cases of postoperative inflammation in the pseudophakic group and 2 cases in the aphakic group. All cases resolved after the frequency of the steroid eyedrops was increased. Three cases of capsule phimosis occurred in the pseudophakic group; in 1 case, the visual axis was occluded and surgical membranectomy was performed 8 months after cataract surgery. There were no cases of aphakic or pseudophakic glaucoma during the 6-month follow-up. Table 3. Intrasubject analysis of preoperative and postoperative mean CCT measurements in unilateral pseudophakic eyes. Mean G SD Time Baseline Postoperative 1 Month CCT (mm) Change (mm) Change (%) P value, within* 6 Months CCT (mm) Change (mm) Change (%) P value, within* Pseudophakic Group (n Z 10) Control Group (n Z 10) 541 G 37 540 G 38 1 ( 12 to 14) .895 534 G 26 19 G 22 3G4 .142 545 G 22 8 G 11 1G2 .171 11 ( 33 to 11) 10 ( 7 to 27) 2 ( 1 to 5) d .240 .163 .164 d 544 G 40 4 G 12 1G2 .192 551 G 39 2G8 0G1 .405 7 ( 18 to 4) 6 ( 5 to 17) 1 ( 1 to 3) d .179 .219 .221 d Mean Paired Difference (95% CI) CI Z confidence interval; CCT Z central corneal thickness *Based on paired t test † Adjusted for baseline based on generalized estimating equation J CATARACT REFRACT SURG - VOL 36, DECEMBER 2010 P Value† CCT CHANGES AFTER CONGENITAL CATARACT SURGERY DISCUSSION Although there are many reports of increased CCT after the removal of congenital cataracts,1–5 none compared the CCT values before cataract removal with the postoperative values. Lupinacci et al.4 measured the CCT in eyes with congenital cataracts and surgical aphakia. They found that aphakic eyes due to congenital cataract extraction had thicker corneas than normal phakic eyes and suggest that the increase in CCT occurs postoperatively. They included no pseudophakic eyes in their study. Muir et al.1 found that the CCT was similar in eyes with pediatric cataract and in normal control eyes and that the CCT increased after cataract surgery. However, in their study, the mean CCT in aphakic eyes was greater than in the control eyes, eyes with cataract, and eyes with pseudophakia. The authors did not mention the percentage of primary and secondary pseudophakia. Simsek et al.2 compared 43 eyes of 43 aphakic and pseudophakic patients after congenital cataract surgery with eyes of 44 healthy age- and sex-matched volunteers. The mean CCT values of the aphakic eyes were significantly greater than in the pseudophakic eyes, in which an IOL had been implanted at the time of congenital cataract surgery. Differences between aphakic eyes and pseudophakic eyes in which an IOL had been implanted secondarily were not significant. Only 10 eyes in their study were pseudophakic, and primary IOL implantation was performed in 5 cases. Simon et al.3 describe increased CCT in aphakic/ pseudophakic children compared with control patients. In their series, only 2 primary pseudophakia patients were included. Nilforushan et al.5 report that the corneas in eyes with extracted congenital cataract were significantly thicker than in normal control eyes. They found no significant difference in the corneal endothelial cell count or morphology between operated eyes and normal eyes. They dismissed endothelial damage as a possible explanation for the increase in CCT after congenital cataract surgery. The authors propose that eyes with congenital cataract have thicker corneas preoperatively. This differs from our findings. All previous studies of the change in CCT after congenital cataract surgery compared the CCT in aphakic/pseudophakic eyes and control eyes; none had access to preoperative CCT values. We believe ours is the first longitudinal study of CCT changes in patients who had congenital cataract extraction. In the current study, the mean CCT in the normal eyes was 558 G 36 mm, similar to values reported by Hossein et al.13 (549 G 46 mm) and Dai et al.14 2045 (563 G 36 mm). We found that the CCT before surgery in eyes with congenital cataract was similar to that in normal eyes and that there was an increase in CCT postoperatively in aphakic eyes but not in pseudophakic eyes. The mechanism of CCT increase after congenital cataract extraction remains a matter of speculation. In normal eyes without cataract, the central cornea is thicker at birth, rapidly decreases in thickness during the first few months of life, and then stabilizes over time.13 This change in corneal thickness occurring in the first months of life indicates that corneal development continues after birth. Development of the cornea is affected by the crystalline lens during the embryological period.15 This effect may continue after birth, and removing the crystalline lens at an early age may stop it. We speculate that the crystalline lens acts as a barrier because substitution of the natural lens with an IOL in pediatric cataract surgery had no effect on CCT in our study. Another theory of the increase in CCT after pediatric cataract surgery is endothelial cell damage at the time of surgery.3,5 Mechanical stress to endothelial cells with unrecognized surgical trauma and irrigation fluids has been proposed as a cause of endothelial cell dysfunction and increased CCT after pediatric cataract surgery. Increased CCT was seen in aphakic eyes but not in pseudophakic eyes in our study. Thus, it is less probable that the increase is due to mechanical stress during cataract surgery because theoretically, endothelial cell trauma would be greater in pseudophakic eyes than in aphakic eyes. There are several reports that primary pseudophakia may be associated with a lower rate of glaucoma following surgery for congenital cataract.16–19 It has been suggested that exposure of maturing angle structures to the potentially harmful effect of vitreous components is a possible factor in developing aphakic glaucoma, and access to the trabecular meshwork is prevented or minimized in the pseudophakic eye by the presence of the IOL.10,16 This finding is a key component of our theory about the barrier effect of the IOL in preventing increased CCT after pediatric cataract surgery. Some authors believe that surgery for congenital cataract at an early age increases the risk for glaucoma whether the eye is aphakic or pseudophakic.20,21 There were no cases of postoperative glaucoma in our series. The mean 6-month postoperative IOP was not greater than the mean preoperative IOP in the aphakic group, although the postoperative CCT values in those eyes was significantly thicker than baseline measurements. This may be because all IOP readings in our study were performed with a Tono-Pen, and this instrument is least affected by CCT when used to measure IOP.22,23 Goldmann applanation tonometry tends to overestimate J CATARACT REFRACT SURG - VOL 36, DECEMBER 2010 2046 CCT CHANGES AFTER CONGENITAL CATARACT SURGERY IOP in pediatric eyes with a thick cornea,10 leading to unnecessary prescription of antiglaucoma medications. Absence of postoperative glaucoma in our series can be attributed to the relatively short follow-up, primary PC IOL implantation in the majority of cases with haptics in the ciliary sulcus instead of in the capsular bag, and surgery at an older age (mean 37.7 months, pseudophakic group; 5.6 months, aphakic group). It was impossible to age match aphakic eyes with pseudophakic eyes in our study because of the limitation of IOL implantation in very young infants; however, we evaluated the role of age by comparing patients of the same age in the 2 groups. After adjustment for age, the mean CCT was significantly greater in the aphakic group than in the pseudophakic group 1 month and 6 months postoperatively (P!.001). Based on these findings, we believe that regardless of patient age, primary pseudophakia has a protective role against increased CCT after pediatric cataract surgery. Several factors control corneal hydration and therefore corneal thickness; these include evaporation, IOP, swelling pressure, endothelial permeability, endothelial fluid pump, endothelial pump rate receptors, and corneal epithelium.24 Our study could not clearly address the reasons for increased CCT in the eyes left aphakic after congenital cataract surgery. Evaluation of the corneal layers’ anatomy and function in eyes with congenital cataract before and after cataract extraction would help elucidate the underlying causes. Our findings are from the first 6 months postoperatively. The results, especially in pseudophakic eyes, may change with a longer follow-up. Another limitation is the small number of patients, especially in the aphakic group, which makes it difficult to generalize the results with certainty. In conclusion, IOP measurement is the most important factor in the diagnosis of glaucoma in children. Therefore, increased corneal thickness in aphakic eyes after cataract extraction and its effect on IOP measurement must be kept in mind. We showed that the CCT increases after surgery and that IOL implantation may have a protective effect. We speculate that vitreous factors could have an important effect on the maturing cornea and that IOL implantation after pediatric cataract surgery appears to protect the cornea against these unknown factors. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. REFERENCES 1. Muir KW, Duncan L, Enyedi LB, Wallace DK, Freedman SF. Central corneal thickness: congenital cataracts and aphakia. Am J Ophthalmol 2007; 144:502–506 2. Simsek T, Mutluay AH, Elgin U, Gursel R, Batman A. Glaucoma and increased central corneal thickness in aphakic and pseudophakic patients after congenital cataract surgery. Br J 19. 20. Ophthalmol 2006; 90:1103–1106. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC1857403/pdf/1103.pdf. Accessed August 19, 2010 Simon JW, O’Malley MR, Gandham SB, Ghaiy R, Zobal-Ratner J, Simmons ST. Central corneal thickness and glaucoma in aphakic and pseudophakic children. J AAPOS 2005; 9:326–329 Lupinacci APC, da Silva Jordão ML, Massa G, Arieta CEL, Costa VP. 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