- Email: [email protected]
Trypan blue as a surgical adjunct in pediatric cataract surgery
ARTICLE
Trypan blue as a surgical adjunct in pediatric cataract surgery Gabrielle Fridman, BS, Allison E. Rizzuti, MD, Jewel Liao, MD, Mark Rolain, MD, James A. Deutsch, MD, Stephen C. Kaufman, MD, PhD
PURPOSE: To study the effect of trypan blue on lens capsule elasticity and ease of completing a continuous curvilinear capsulorhexis (CCC) in a sheep lens model and to subsequently observe the effects of trypan blue in the surgical setting of 3 pediatric patients. SETTING: State University of New York, Downstate Medical Center, Brooklyn, New York, USA. DESIGN: Prospective case series. METHODS: Twenty-four lenses were excised from fresh sheep globes. Twelve lenses were immersed in trypan blue for 2.5 minutes, and 12 lenses were immersed in a balanced salt solution for 2.5 minutes. Ease of completion of CCC was graded, and intralenticular pressure was quantified. A pediatric cataract surgeon used trypan blue to stain the lens capsules of 3 children during cataract surgery. The surgeon noted the effects of trypan blue on capsule elasticity and on the ease of completion of the CCC. RESULTS: Lenses immersed in trypan blue had a mean score of 2.58 in ease of completion of capsulorhexis compared with the control group (1.5) (P Z .031). Capsulorhexis was successfully completed in 91.7% of trypan blue cases compared with 58.3% of controls. Immersion in trypan blue decreased the intralenticular pressure by a mean of 4.5 mm Hg (P Z .025). Successful capsulorhexis was completed in the 3 pediatric cases. CONCLUSION: Trypan blue improved the success rate of CCC completion in the sheep lens by decreasing lens capsule elasticity. Financial Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2016; 42:1774–1778 Q 2016 ASCRS and ESCRS
Submitted: July 4, 2016. Final revision submitted: October 10, 2016. Accepted: October 11, 2016. From the Department of Ophthalmology (Fridman, Rizzuti, Liao, Deutsch, Kaufman), State University of New York, Downstate Medical Center, Brooklyn, New York, and the Department of Ophthalmology (Rolain), Beaumont Hospital, Royal Oak, Michigan, USA. Supported by a challenge grant from Research to Prevent Blindness, to the Department of Ophthalmology, SUNY Downstate Medical Center. Corresponding author: Allison E. Rizzuti, MD, 70 Washington Street, Apartment 4Q, Brooklyn, New York 11201, USA. E-mail: [email protected].
1774
Q 2016 ASCRS and ESCRS Published by Elsevier Inc.
Cataracts in the pediatric age group can result in permanent blindness if they are not removed. Management of a pediatric cataract requires surgery to provide a clear visual axis and to prevent subsequent amblyopia.1 At present, the procedure of choice for pediatric patients is cataract extraction using phacoaspiration combined with primary posterior capsulotomy, anterior vitrectomy, and possible IOL implantation in the capsular bag. Trypan blue is a dye that selectively stains the basement membrane of the anterior lens capsule and has no known toxicity when used at a clinical concentration approved by the U.S. Food and Drug Administration (FDA).1,2 It is often used in adult cataract surgery to better visualize the lenticular capsule for creation of http://dx.doi.org/10.1016/j.jcrs.2016.10.012 0886-3350
TRYPAN BLUE IN PEDIATRIC CATARACT SURGERY
a continuous curvilinear capsulorhexis (CCC) during cases that fail to provide an adequate red reflex (eg, eyes with dense cataract). Apart from improved visualization, trypan blue is also thought to reduce the elasticity of the lens capsule.3 Although this might be undesirable in the adult, it could be beneficial in pediatric cases in which the lens capsule can often be too elastic to perform a safe anterior CCC and posterior CCC. Difficulty creating a CCC can lead to radial capsule tears, poor capsule support for IOL placement, and other associated complications.1 In this study, we quantified the ease of creating a CCC in sheep eyes with and without the use of trypan blue 0.06%. We also quantified the change in lens capsule elasticity and the change in intralenticular pressure after application of trypan blue 0.06%. In addition, we present 3 case studies that illustrate the effect of trypan blue in the surgical setting during pediatric cataract extractions. Collectively, the data provide insight into the effects of trypan blue during CCC and highlight its potential beneficial effect when performing a CCC in pediatric cataract surgery. MATERIALS AND METHODS Ex Vivo Study Crystalline lenses were removed from 24 ex vivo fresh sheep eyes after hemisection about the equator of the globe.
Reagents The FDA-approved 0.06% trypan blue solution (Dutch Ophthalmic USA) was used for this study. The lenses were immersed in trypan blue 0.06% for 2.5 minutes (n Z 12) or in the sham treatment of a balanced salt solution for 2.5 minutes (n Z 12).
1775
radial tear or Argentinian flag signA was given a grade of 0. One surgeon (A.R.) performed and graded each capsulorhexis, alternating between the treatment group and the control group.
Intralenticular Pressure Intact lens capsule resistance to compression was measured with a Schiotz tonometer to determine intralenticular pressure change before and after trypan blue treatment (4 pretreatment and 4 posttreatment measurements) with 0.06% trypan blue as described above (n Z 4).
Statistical Analyses A 1-tailed Student t test was used to analyze the ease of capsulorhexis before and after treatment with 0.06% trypan blue. A 2-tailed paired Student t test was used to analyze the difference in intralenticular pressure before and after treatment with 0.06% trypan blue. A P value less than 0.05 was considered statistically significant for all analyses.
RESULTS Effect of Trypan Blue on Capsulorhexis Figure 2 shows that performing a capsulorhexis in lenses treated with trypan blue was markedly less difficult to perform, with a mean score of 2.58 out of 4, compared to the sham group that scored a mean 1.5 out of 4 (P Z .031). Moreover, for lenses receiving the sham treatment, a successful capsulorhexis could be completed in 7 eyes (58.3%) only. In 5 eyes, the capsulorhexis was abandoned as the capsule tear extended radially. Lenses treated with trypan blue had a higher success
Continuous Curvilinear Capsulorhexis A CCC was then attempted on each sheep lens using a cystotome and a Utrata forceps while positioned on a surgical drape (Figure 1). Ease of capsulorhexis was graded on a 4-point scale (1 Z difficult, 4 Z undemanding). A failed capsulorhexis resulting from a
Figure 1. Completed CCC in a sheep lens that was immersed in trypan blue.
Figure 2. Ease of capsulorhexis with and without capsule staining with trypan blue 0.06% dye on a 4-point scale. The shorter the bar, the greater the difficulty (1 Z difficult; 4 Z undemanding) (12 per group).
J CATARACT REFRACT SURG - VOL 42, DECEMBER 2016
1776
TRYPAN BLUE IN PEDIATRIC CATARACT SURGERY
rate (91.7%), with 11 of 12 successfully completed procedures. In 1 lens in the treatment group, the capsulorhexis was abandoned because of spontaneous tears extending to the periphery immediately after puncture of the capsule (Argentinian flag sign). Effect of Trypan Blue on Intralenticular Pressure As seen in Figure 3, after administration of trypan blue, the lens pressure decreased by a mean of 4.5 mm Hg (P Z .025). Pediatric Case Studies Trypan blue 0.06% ophthalmic solution was used to stain the lens capsule in the following 3 pediatric cataract cases. For all 3 cases, the surgeon observed that the lens capsule was less elastic when stained with trypan blue than with his routine cases that do not use dye and that completion of the capsulorhexis was less of a challenge. Case 1 A 12-year-old Nigerian boy with history of
myopia presented with blurry vision in the right eye. Uncorrected distance visual acuity (UDVA) was hand motions in the right eye and 20/20 in his left eye. Slitlamp examination was significant for a mature white cataract in the right eye. He and his parents denied a history of trauma or infection. The patient had uneventful cataract extraction, anterior vitrectomy after central posterior capsule removal, and IOL implantation. An anterior CCC was easily completed with a cystotome and a Utrata forceps after use of trypan blue, which was injected into the anterior chamber
and removed after 1.5 minutes. The postoperative visual acuity was 20/20. Case 2 A boy aged 2 years and 11 months with no
medical or family history presented with bilateral cataracts (left eye O right eye). Preoperatively, he was able to fix and follow with the right eye only. Cataract extraction, anterior vitrectomy after central posterior capsule removal, and IOL implantation were performed in the left eye followed by the right eye. Successful anterior CCCs were performed with a cystotome and a Utrata forceps after trypan blue was injected into the anterior chamber and removed after 1.5 minutes. Postoperative UDVA stabilized to bilateral fixing and following over the subsequent 3 weeks. A 3-month-old Yemeni boy with no medical history and with a family history significant for consanguinity and paternal poor vision since childhood presented with bilateral cataract. On physical examination, the patient was noted to have bilateral horizontal and vertical nystagmus; UDVA could not be assessed because of photophobia. The patient had cataract extraction and anterior vitrectomy after central posterior capsule removal in the right eye followed by the left eye 2 weeks later. With the use of trypan blue, which was injected into the anterior chamber and removed after 1.5 minutes, a successful anterior and posterior CCC was created using an anterior vitrector during both surgeries. The patient was able to fix and follow with each eye 1 month later.
Case 3
DISCUSSION
Figure 3. Intralenticular pressure before and after treatment with 0.06% trypan blue. Bars represent the mean G SEM (4 per group).
A CCC is performed during cataract surgery to allow safer manipulation of the lens during phacoemulsification and to allow for insertion, better stabilization, and centration of an IOL in the capsular bag. It is essential to visualize the lens capsule to ensure a successful capsulorhexis. Without the use of a technique to discriminate the anterior capsule from the underlying lens tissue, there is a higher risk for radial capsule tears and associated complications in cases with a poor red reflex. Dyes that stain the lens capsule have therefore been used to increase visibility and enhance ease of anterior CCCs in adult cataract surgery.1 Manual CCC is the most commonly performed anterior capsulotomy technique in adult cataract surgery because it is relatively easy to complete and yields a low rate of radial tears.4 However, being that the pediatric lens capsule has approximately 5 times the tensile strength and double the extensibility of an adult capsule, it requires application of greater force before tearing begins.4 The risk for complications during the creation of a CCC in a child is therefore greater. This is evidenced by a study evaluating the incidence of
J CATARACT REFRACT SURG - VOL 42, DECEMBER 2016
TRYPAN BLUE IN PEDIATRIC CATARACT SURGERY
anterior capsule tears in a pediatric population,4 which found an expert surgeon's 10-year CCC tear rate to be 6.4%. Comparatively, a review article on the incidence of anterior capsule tears in CCCs performed by expert surgeons in an adult population5 found the rate to be significantly lower (0.5%). Pediatric cataract surgery is further complicated by need for a central posterior CCC (PCCC). Before the advent of PCCC, when the posterior capsule was left intact, posterior capsule opacification (PCO) was a rapid and virtually inevitable cause of poor visual outcomes in children.6 Posterior capsule opacification results from the abnormal proliferation of lens epithelial cells on the capsule at the time of cataract surgery that migrate to the posterior capsule, resulting in visual axis obscuration and decreased vision.2,7 To help avoid PCO, retain a clear visual axis, and hold the IOL in its proper location while preventing amblyopia, it is recommended that a primary posterior capsulorhexis be performed; that is, a PCCC, possibly combined with optic capture of the IOL, anterior vitrectomy, or both.1 Similar to an anterior CCC (ACCC), performing a PCCC in children can be difficult because of the thin, transparent, and elastic nature of the capsule. This is further complicated by decreased visibility and positive vitreous pressure.8 The challenges of creating a manual ACCC and PCCC have led surgeons to search for alternative methods to use in children. Alternatives currently include vitrectorhexis, radiofrequency diathermy, and use of a Fugo plasma blade.9 On review of the CCC techniques, extensibility and edge characteristics were best produced by a manual CCC, which currently remains the gold-standard technique.9 Saini et al.8 used trypan blue to improve the visibility of the lens capsules and address the challenges associated with a manual ACCC and PCCC in pediatric cataract surgery. In agreement with their results, our successful completion of a CCC with use of trypan blue was greater than 90% while completion without dye was just over 50%. Our data confirmed that the ease of completing a continuous capsulorhexis in ovine lens capsules is significantly improved with the use of trypan blue (P Z .0308). The dye allowed the surgeon to more easily visualize the lens capsule and most important, it altered the elasticity of the lens capsule, leading to an increased rate of successful CCC completion. We found this in an animal model that has an elastic lens capsule similar to that found in children. Comparable findings were observed using trypan blue in our 3 pediatric cataract surgery patients. In addition, we found that trypan blue decreases intralenticular pressure. This is particularly relevant because high intraocular pressure is a specific
1777
characteristic of the pediatric eye, especially in children younger than 2 years.10 When measuring the pressure of the lens with a Schiotz tonometer, 0.06% trypan blue significantly decreased intralenticular pressure after application. The electrolyte and water content of the lens is similar to that of the typical cell, with gradients maintained via chemical and electrical energy provided by pumps such as sodium–potassium adenosine triphosphatase. The lens, therefore, functions as an osmometer and is able to regulate volume, and thus pressure, to maintain a steady state.11 The osmolarity of 0.06% trypan blue can be as high as 314 mOsm.12 The normal human eye has an osmolarity of 290 mOsm.11 Therefore, we hypothesize that trypan blue exerts an osmotic effect on the lens, leading to a decrease in intralenticular pressure. Although our results were statistically significant (P Z .025), weaknesses of the study include an animal model that might not fully simulate in vivo pediatric cataract surgery. In our study, the entire crystalline lens was submerged in 0.06% trypan blue, while in pediatric cataract surgery only the anterior lens capsule is stained. Furthermore, our surgeon used subjective rather than objective criteria to evaluate elasticity and was not blinded to the 2 groups, possibly leading to observer bias. Future studies are needed to explore the mechanism behind the decreased intralenticular pressure as well as to confirm that this is beneficial in human subjects. In conclusion, the effect of trypan blue dye might reduce the elasticity of the pediatric lens capsule, which might be beneficial if a CCC is used in pediatric cataract surgery. However, further studies are needed. WHAT WAS KNOWN Completing a capsulorhexis in children is more difficult because of the increased elasticity of the lens capsule. Although trypan blue primarily aids in the visualization of the lens capsule during cataract surgery, it is also thought to reduce the capsule’s elasticity. WHAT THIS PAPER ADDS Immersion in trypan blue facilitated the completion of the capsulorhexis in sheep eyes by decreasing the elasticity of the lens capsule. Immersion in trypan blue decreased intralenticular pressure, possibly by the dye’s osmotic effect on the lens. The effect of trypan blue dye might reduce the elasticity of the pediatric lens capsule, which could be beneficial if a CCC is used in pediatric cataract surgery; however, further studies are needed.
J CATARACT REFRACT SURG - VOL 42, DECEMBER 2016
1778
TRYPAN BLUE IN PEDIATRIC CATARACT SURGERY
REFERENCES 1. Melles GRJ, de Waard PWT, Pameyer JH, Beekhuis WH. Trypan blue capsule staining to visualize the capsulorhexis in cataract surgery. J Cataract Refract Surg 1999; 25:7–9 2. Singh AJ, Sarodia UA, Brown L, Jagjivan R, Sampath R. A histological analysis of lens capsules stained with trypan blue for capsulorrhexis in phacoemulsification cataract surgery. Eye 2003; 17:567–570. Available at: http://www.nature.com/eye/ journal/v17/n5/pdf/6700440a.pdf. Accessed October 20, 2016 €rl E, Pham D-T. Biomechanical changes in the 3. Wollensak G, Spo anterior lens capsule after trypan blue staining. J Cataract Refract Surg 2004; 30:1526–1530 4. Wilson ME Jr. Anterior lens capsule management in pediatric cataract surgery. Trans Am Ophthalmol Soc 2004; 102:391– 422. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC1280111/pdf/tao102pg391.pdf. Accessed October 20, 2016 5. Chang DF. Current outcomes with cataract surgery: Can we do better? In: Krueger RR, Talamo JH, Lindstrom RL, eds, Textbook of Refractive Laser Assisted Cataract Surgery (ReLACS). New York, NY, Springer, 2013; 9–16. Available at: http://www. springer.com/cda/content/document/cda_downloaddocument/ 9781461410096-c1.pdf?SGWIDZ0-0-45-1365806-p1741951 70. Accessed October 20, 2016 6. Mohammadpour M, Erfanian R, Karimi N. Capsulorhexis: pearls and pitfalls. Saudi J Ophthalmol 2012; 26:33–40. Available at: http://www.saudiophthaljournal.com/article/S1319-4534(11)001 27-5/pdf. Accessed October 20, 2016 7. Zemaitien e_ R. [Posterior capsule opacification: incidence and pathogenesis] [Lithuanian]. Medicina (Kaunas) 2002; 39:830– 837. Available at: http://medicina.lsmuni.lt/med/0309/0309-03l. pdf. Accessed October 20, 2016 8. Saini JS, Jain AK, Sukhija J, Gupta P, Saroha V. Anterior and posterior capsulorhexis in pediatric cataract surgery with or without trypan blue dye; randomized prospective clinical study. J Cataract Refract Surg 2003; 29:1733–1737
9. Vasavada AR, Nihalani BR. Pediatric cataract surgery. Curr Opin Ophthalmol 2006; 17:54–61 10. Ram J, Sukhija J. Pediatric cataract surgery: current concepts. J Int Med Sci Acad 2010; 23:132–137. Available at: http:// medind.nic.in/jav/t10/i3/javt10i3p132.pdf. Accessed October 20, 2016 11. Garg A. Biochemistry of the lens. In: Agarwal S, Agarwal A, JL, Pandey SK, Agarwal A, eds, TextApple DJ, Buratto L, Alio book of Ophthalmology. Volume 1: Basic Sciences, Optics and Refraction, Neuro-Ophthalmology, Strabismus. New Delhi, India, Jaypee Brothers, 2002; 117–119 s J, Dib E, 12. Rodrigues EB, Costa EF, Penha FM, Melo GB, Botto €fling-Lima AL, Furlani B, Lima VC, Maia M, Meyer CH, Ho Farah ME. The use of vital dyes in ocular surgery. Surv Ophthalmol 2009; 54:576–617
OTHER CITED MATERIAL A. Perrone DM. Argentinean flag sign is most common complication for intumescent cataracts. Ocular Surgery News U.S. edition Dec. 15, 2000. Available at: http://www.healio.com/ ophthalmology/cataract-surgery/news/print/ocular-surgery-ne ws/%7B33d6fae9-280c-4353-8abf-fd0c830975a8%7D/argentinean-flag-sign-is-most-common-complication-for-intumesce nt-cataract. Accessed October 20, 2016
J CATARACT REFRACT SURG - VOL 42, DECEMBER 2016
First author: Gabrielle Fridman, BS Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, New York, USA
Trypan blue as a surgical adjunct in pediatric cataract surgery Gabrielle Fridman, BS, Allison E. Rizzuti, MD, Jewel Liao, MD, Mark Rolain, MD, James A. Deutsch, MD, Stephen C. Kaufman, MD, PhD
PURPOSE: To study the effect of trypan blue on lens capsule elasticity and ease of completing a continuous curvilinear capsulorhexis (CCC) in a sheep lens model and to subsequently observe the effects of trypan blue in the surgical setting of 3 pediatric patients. SETTING: State University of New York, Downstate Medical Center, Brooklyn, New York, USA. DESIGN: Prospective case series. METHODS: Twenty-four lenses were excised from fresh sheep globes. Twelve lenses were immersed in trypan blue for 2.5 minutes, and 12 lenses were immersed in a balanced salt solution for 2.5 minutes. Ease of completion of CCC was graded, and intralenticular pressure was quantified. A pediatric cataract surgeon used trypan blue to stain the lens capsules of 3 children during cataract surgery. The surgeon noted the effects of trypan blue on capsule elasticity and on the ease of completion of the CCC. RESULTS: Lenses immersed in trypan blue had a mean score of 2.58 in ease of completion of capsulorhexis compared with the control group (1.5) (P Z .031). Capsulorhexis was successfully completed in 91.7% of trypan blue cases compared with 58.3% of controls. Immersion in trypan blue decreased the intralenticular pressure by a mean of 4.5 mm Hg (P Z .025). Successful capsulorhexis was completed in the 3 pediatric cases. CONCLUSION: Trypan blue improved the success rate of CCC completion in the sheep lens by decreasing lens capsule elasticity. Financial Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2016; 42:1774–1778 Q 2016 ASCRS and ESCRS
Submitted: July 4, 2016. Final revision submitted: October 10, 2016. Accepted: October 11, 2016. From the Department of Ophthalmology (Fridman, Rizzuti, Liao, Deutsch, Kaufman), State University of New York, Downstate Medical Center, Brooklyn, New York, and the Department of Ophthalmology (Rolain), Beaumont Hospital, Royal Oak, Michigan, USA. Supported by a challenge grant from Research to Prevent Blindness, to the Department of Ophthalmology, SUNY Downstate Medical Center. Corresponding author: Allison E. Rizzuti, MD, 70 Washington Street, Apartment 4Q, Brooklyn, New York 11201, USA. E-mail: [email protected].
1774
Q 2016 ASCRS and ESCRS Published by Elsevier Inc.
Cataracts in the pediatric age group can result in permanent blindness if they are not removed. Management of a pediatric cataract requires surgery to provide a clear visual axis and to prevent subsequent amblyopia.1 At present, the procedure of choice for pediatric patients is cataract extraction using phacoaspiration combined with primary posterior capsulotomy, anterior vitrectomy, and possible IOL implantation in the capsular bag. Trypan blue is a dye that selectively stains the basement membrane of the anterior lens capsule and has no known toxicity when used at a clinical concentration approved by the U.S. Food and Drug Administration (FDA).1,2 It is often used in adult cataract surgery to better visualize the lenticular capsule for creation of http://dx.doi.org/10.1016/j.jcrs.2016.10.012 0886-3350
TRYPAN BLUE IN PEDIATRIC CATARACT SURGERY
a continuous curvilinear capsulorhexis (CCC) during cases that fail to provide an adequate red reflex (eg, eyes with dense cataract). Apart from improved visualization, trypan blue is also thought to reduce the elasticity of the lens capsule.3 Although this might be undesirable in the adult, it could be beneficial in pediatric cases in which the lens capsule can often be too elastic to perform a safe anterior CCC and posterior CCC. Difficulty creating a CCC can lead to radial capsule tears, poor capsule support for IOL placement, and other associated complications.1 In this study, we quantified the ease of creating a CCC in sheep eyes with and without the use of trypan blue 0.06%. We also quantified the change in lens capsule elasticity and the change in intralenticular pressure after application of trypan blue 0.06%. In addition, we present 3 case studies that illustrate the effect of trypan blue in the surgical setting during pediatric cataract extractions. Collectively, the data provide insight into the effects of trypan blue during CCC and highlight its potential beneficial effect when performing a CCC in pediatric cataract surgery. MATERIALS AND METHODS Ex Vivo Study Crystalline lenses were removed from 24 ex vivo fresh sheep eyes after hemisection about the equator of the globe.
Reagents The FDA-approved 0.06% trypan blue solution (Dutch Ophthalmic USA) was used for this study. The lenses were immersed in trypan blue 0.06% for 2.5 minutes (n Z 12) or in the sham treatment of a balanced salt solution for 2.5 minutes (n Z 12).
1775
radial tear or Argentinian flag signA was given a grade of 0. One surgeon (A.R.) performed and graded each capsulorhexis, alternating between the treatment group and the control group.
Intralenticular Pressure Intact lens capsule resistance to compression was measured with a Schiotz tonometer to determine intralenticular pressure change before and after trypan blue treatment (4 pretreatment and 4 posttreatment measurements) with 0.06% trypan blue as described above (n Z 4).
Statistical Analyses A 1-tailed Student t test was used to analyze the ease of capsulorhexis before and after treatment with 0.06% trypan blue. A 2-tailed paired Student t test was used to analyze the difference in intralenticular pressure before and after treatment with 0.06% trypan blue. A P value less than 0.05 was considered statistically significant for all analyses.
RESULTS Effect of Trypan Blue on Capsulorhexis Figure 2 shows that performing a capsulorhexis in lenses treated with trypan blue was markedly less difficult to perform, with a mean score of 2.58 out of 4, compared to the sham group that scored a mean 1.5 out of 4 (P Z .031). Moreover, for lenses receiving the sham treatment, a successful capsulorhexis could be completed in 7 eyes (58.3%) only. In 5 eyes, the capsulorhexis was abandoned as the capsule tear extended radially. Lenses treated with trypan blue had a higher success
Continuous Curvilinear Capsulorhexis A CCC was then attempted on each sheep lens using a cystotome and a Utrata forceps while positioned on a surgical drape (Figure 1). Ease of capsulorhexis was graded on a 4-point scale (1 Z difficult, 4 Z undemanding). A failed capsulorhexis resulting from a
Figure 1. Completed CCC in a sheep lens that was immersed in trypan blue.
Figure 2. Ease of capsulorhexis with and without capsule staining with trypan blue 0.06% dye on a 4-point scale. The shorter the bar, the greater the difficulty (1 Z difficult; 4 Z undemanding) (12 per group).
J CATARACT REFRACT SURG - VOL 42, DECEMBER 2016
1776
TRYPAN BLUE IN PEDIATRIC CATARACT SURGERY
rate (91.7%), with 11 of 12 successfully completed procedures. In 1 lens in the treatment group, the capsulorhexis was abandoned because of spontaneous tears extending to the periphery immediately after puncture of the capsule (Argentinian flag sign). Effect of Trypan Blue on Intralenticular Pressure As seen in Figure 3, after administration of trypan blue, the lens pressure decreased by a mean of 4.5 mm Hg (P Z .025). Pediatric Case Studies Trypan blue 0.06% ophthalmic solution was used to stain the lens capsule in the following 3 pediatric cataract cases. For all 3 cases, the surgeon observed that the lens capsule was less elastic when stained with trypan blue than with his routine cases that do not use dye and that completion of the capsulorhexis was less of a challenge. Case 1 A 12-year-old Nigerian boy with history of
myopia presented with blurry vision in the right eye. Uncorrected distance visual acuity (UDVA) was hand motions in the right eye and 20/20 in his left eye. Slitlamp examination was significant for a mature white cataract in the right eye. He and his parents denied a history of trauma or infection. The patient had uneventful cataract extraction, anterior vitrectomy after central posterior capsule removal, and IOL implantation. An anterior CCC was easily completed with a cystotome and a Utrata forceps after use of trypan blue, which was injected into the anterior chamber
and removed after 1.5 minutes. The postoperative visual acuity was 20/20. Case 2 A boy aged 2 years and 11 months with no
medical or family history presented with bilateral cataracts (left eye O right eye). Preoperatively, he was able to fix and follow with the right eye only. Cataract extraction, anterior vitrectomy after central posterior capsule removal, and IOL implantation were performed in the left eye followed by the right eye. Successful anterior CCCs were performed with a cystotome and a Utrata forceps after trypan blue was injected into the anterior chamber and removed after 1.5 minutes. Postoperative UDVA stabilized to bilateral fixing and following over the subsequent 3 weeks. A 3-month-old Yemeni boy with no medical history and with a family history significant for consanguinity and paternal poor vision since childhood presented with bilateral cataract. On physical examination, the patient was noted to have bilateral horizontal and vertical nystagmus; UDVA could not be assessed because of photophobia. The patient had cataract extraction and anterior vitrectomy after central posterior capsule removal in the right eye followed by the left eye 2 weeks later. With the use of trypan blue, which was injected into the anterior chamber and removed after 1.5 minutes, a successful anterior and posterior CCC was created using an anterior vitrector during both surgeries. The patient was able to fix and follow with each eye 1 month later.
Case 3
DISCUSSION
Figure 3. Intralenticular pressure before and after treatment with 0.06% trypan blue. Bars represent the mean G SEM (4 per group).
A CCC is performed during cataract surgery to allow safer manipulation of the lens during phacoemulsification and to allow for insertion, better stabilization, and centration of an IOL in the capsular bag. It is essential to visualize the lens capsule to ensure a successful capsulorhexis. Without the use of a technique to discriminate the anterior capsule from the underlying lens tissue, there is a higher risk for radial capsule tears and associated complications in cases with a poor red reflex. Dyes that stain the lens capsule have therefore been used to increase visibility and enhance ease of anterior CCCs in adult cataract surgery.1 Manual CCC is the most commonly performed anterior capsulotomy technique in adult cataract surgery because it is relatively easy to complete and yields a low rate of radial tears.4 However, being that the pediatric lens capsule has approximately 5 times the tensile strength and double the extensibility of an adult capsule, it requires application of greater force before tearing begins.4 The risk for complications during the creation of a CCC in a child is therefore greater. This is evidenced by a study evaluating the incidence of
J CATARACT REFRACT SURG - VOL 42, DECEMBER 2016
TRYPAN BLUE IN PEDIATRIC CATARACT SURGERY
anterior capsule tears in a pediatric population,4 which found an expert surgeon's 10-year CCC tear rate to be 6.4%. Comparatively, a review article on the incidence of anterior capsule tears in CCCs performed by expert surgeons in an adult population5 found the rate to be significantly lower (0.5%). Pediatric cataract surgery is further complicated by need for a central posterior CCC (PCCC). Before the advent of PCCC, when the posterior capsule was left intact, posterior capsule opacification (PCO) was a rapid and virtually inevitable cause of poor visual outcomes in children.6 Posterior capsule opacification results from the abnormal proliferation of lens epithelial cells on the capsule at the time of cataract surgery that migrate to the posterior capsule, resulting in visual axis obscuration and decreased vision.2,7 To help avoid PCO, retain a clear visual axis, and hold the IOL in its proper location while preventing amblyopia, it is recommended that a primary posterior capsulorhexis be performed; that is, a PCCC, possibly combined with optic capture of the IOL, anterior vitrectomy, or both.1 Similar to an anterior CCC (ACCC), performing a PCCC in children can be difficult because of the thin, transparent, and elastic nature of the capsule. This is further complicated by decreased visibility and positive vitreous pressure.8 The challenges of creating a manual ACCC and PCCC have led surgeons to search for alternative methods to use in children. Alternatives currently include vitrectorhexis, radiofrequency diathermy, and use of a Fugo plasma blade.9 On review of the CCC techniques, extensibility and edge characteristics were best produced by a manual CCC, which currently remains the gold-standard technique.9 Saini et al.8 used trypan blue to improve the visibility of the lens capsules and address the challenges associated with a manual ACCC and PCCC in pediatric cataract surgery. In agreement with their results, our successful completion of a CCC with use of trypan blue was greater than 90% while completion without dye was just over 50%. Our data confirmed that the ease of completing a continuous capsulorhexis in ovine lens capsules is significantly improved with the use of trypan blue (P Z .0308). The dye allowed the surgeon to more easily visualize the lens capsule and most important, it altered the elasticity of the lens capsule, leading to an increased rate of successful CCC completion. We found this in an animal model that has an elastic lens capsule similar to that found in children. Comparable findings were observed using trypan blue in our 3 pediatric cataract surgery patients. In addition, we found that trypan blue decreases intralenticular pressure. This is particularly relevant because high intraocular pressure is a specific
1777
characteristic of the pediatric eye, especially in children younger than 2 years.10 When measuring the pressure of the lens with a Schiotz tonometer, 0.06% trypan blue significantly decreased intralenticular pressure after application. The electrolyte and water content of the lens is similar to that of the typical cell, with gradients maintained via chemical and electrical energy provided by pumps such as sodium–potassium adenosine triphosphatase. The lens, therefore, functions as an osmometer and is able to regulate volume, and thus pressure, to maintain a steady state.11 The osmolarity of 0.06% trypan blue can be as high as 314 mOsm.12 The normal human eye has an osmolarity of 290 mOsm.11 Therefore, we hypothesize that trypan blue exerts an osmotic effect on the lens, leading to a decrease in intralenticular pressure. Although our results were statistically significant (P Z .025), weaknesses of the study include an animal model that might not fully simulate in vivo pediatric cataract surgery. In our study, the entire crystalline lens was submerged in 0.06% trypan blue, while in pediatric cataract surgery only the anterior lens capsule is stained. Furthermore, our surgeon used subjective rather than objective criteria to evaluate elasticity and was not blinded to the 2 groups, possibly leading to observer bias. Future studies are needed to explore the mechanism behind the decreased intralenticular pressure as well as to confirm that this is beneficial in human subjects. In conclusion, the effect of trypan blue dye might reduce the elasticity of the pediatric lens capsule, which might be beneficial if a CCC is used in pediatric cataract surgery. However, further studies are needed. WHAT WAS KNOWN Completing a capsulorhexis in children is more difficult because of the increased elasticity of the lens capsule. Although trypan blue primarily aids in the visualization of the lens capsule during cataract surgery, it is also thought to reduce the capsule’s elasticity. WHAT THIS PAPER ADDS Immersion in trypan blue facilitated the completion of the capsulorhexis in sheep eyes by decreasing the elasticity of the lens capsule. Immersion in trypan blue decreased intralenticular pressure, possibly by the dye’s osmotic effect on the lens. The effect of trypan blue dye might reduce the elasticity of the pediatric lens capsule, which could be beneficial if a CCC is used in pediatric cataract surgery; however, further studies are needed.
J CATARACT REFRACT SURG - VOL 42, DECEMBER 2016
1778
TRYPAN BLUE IN PEDIATRIC CATARACT SURGERY
REFERENCES 1. Melles GRJ, de Waard PWT, Pameyer JH, Beekhuis WH. Trypan blue capsule staining to visualize the capsulorhexis in cataract surgery. J Cataract Refract Surg 1999; 25:7–9 2. Singh AJ, Sarodia UA, Brown L, Jagjivan R, Sampath R. A histological analysis of lens capsules stained with trypan blue for capsulorrhexis in phacoemulsification cataract surgery. Eye 2003; 17:567–570. Available at: http://www.nature.com/eye/ journal/v17/n5/pdf/6700440a.pdf. Accessed October 20, 2016 €rl E, Pham D-T. Biomechanical changes in the 3. Wollensak G, Spo anterior lens capsule after trypan blue staining. J Cataract Refract Surg 2004; 30:1526–1530 4. Wilson ME Jr. Anterior lens capsule management in pediatric cataract surgery. Trans Am Ophthalmol Soc 2004; 102:391– 422. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC1280111/pdf/tao102pg391.pdf. Accessed October 20, 2016 5. Chang DF. Current outcomes with cataract surgery: Can we do better? In: Krueger RR, Talamo JH, Lindstrom RL, eds, Textbook of Refractive Laser Assisted Cataract Surgery (ReLACS). New York, NY, Springer, 2013; 9–16. Available at: http://www. springer.com/cda/content/document/cda_downloaddocument/ 9781461410096-c1.pdf?SGWIDZ0-0-45-1365806-p1741951 70. Accessed October 20, 2016 6. Mohammadpour M, Erfanian R, Karimi N. Capsulorhexis: pearls and pitfalls. Saudi J Ophthalmol 2012; 26:33–40. Available at: http://www.saudiophthaljournal.com/article/S1319-4534(11)001 27-5/pdf. Accessed October 20, 2016 7. Zemaitien e_ R. [Posterior capsule opacification: incidence and pathogenesis] [Lithuanian]. Medicina (Kaunas) 2002; 39:830– 837. Available at: http://medicina.lsmuni.lt/med/0309/0309-03l. pdf. Accessed October 20, 2016 8. Saini JS, Jain AK, Sukhija J, Gupta P, Saroha V. Anterior and posterior capsulorhexis in pediatric cataract surgery with or without trypan blue dye; randomized prospective clinical study. J Cataract Refract Surg 2003; 29:1733–1737
9. Vasavada AR, Nihalani BR. Pediatric cataract surgery. Curr Opin Ophthalmol 2006; 17:54–61 10. Ram J, Sukhija J. Pediatric cataract surgery: current concepts. J Int Med Sci Acad 2010; 23:132–137. Available at: http:// medind.nic.in/jav/t10/i3/javt10i3p132.pdf. Accessed October 20, 2016 11. Garg A. Biochemistry of the lens. In: Agarwal S, Agarwal A, JL, Pandey SK, Agarwal A, eds, TextApple DJ, Buratto L, Alio book of Ophthalmology. Volume 1: Basic Sciences, Optics and Refraction, Neuro-Ophthalmology, Strabismus. New Delhi, India, Jaypee Brothers, 2002; 117–119 s J, Dib E, 12. Rodrigues EB, Costa EF, Penha FM, Melo GB, Botto €fling-Lima AL, Furlani B, Lima VC, Maia M, Meyer CH, Ho Farah ME. The use of vital dyes in ocular surgery. Surv Ophthalmol 2009; 54:576–617
OTHER CITED MATERIAL A. Perrone DM. Argentinean flag sign is most common complication for intumescent cataracts. Ocular Surgery News U.S. edition Dec. 15, 2000. Available at: http://www.healio.com/ ophthalmology/cataract-surgery/news/print/ocular-surgery-ne ws/%7B33d6fae9-280c-4353-8abf-fd0c830975a8%7D/argentinean-flag-sign-is-most-common-complication-for-intumesce nt-cataract. Accessed October 20, 2016
J CATARACT REFRACT SURG - VOL 42, DECEMBER 2016
First author: Gabrielle Fridman, BS Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, New York, USA