1010
ARTICLE
Hydrogel ocular sealant for clear corneal incisions in cataract surgery Nambi Nallasamy, MD, Karen E. Grove, MD, Gary L. Legault, MD, Melissa B. Daluvoy, MD, Terry Kim, MD
Purpose: To assess the relationship between use of a hydrogel ocular sealant (Resure) to secure clear corneal incisions (CCIs) in cataract surgery and surgeon efficiency, patient symptomatology, and postoperative results. Setting: Duke University Eye Center, Durham, North Carolina, USA.
Design: Retrospective case series. Methods: A 1:1 matched cohort of hydrogel sealant exposure– discordant eyes of cataract surgery patients was retrospectively generated. Consecutive patients who had bilateral cataract surgery during the study period and in whom the hydrogel sealant was used to secure the CCI in only 1 of the 2 eyes were included in the study. The relationship between use of the hydrogel sealant and surgical time, 1-day postoperative foreign-body sensation,
T
he transition from scleral to clear corneal incisions (CCIs) for cataract surgery has been facilitated by the development of phacoemulsification and foldable intraocular lenses (IOLs). The CCI is generally intended to be self-sealing, but studies indicate that wound construction has a significant impact on the rate of wound leak at the completion of cataract surgery.1–4 A recent study involving single-plane CCIs for cataract surgery reported a rate of spontaneous wound leak of 48.8% and a rate of wound leak with 1 ounce or less of pressure of 97.6%.4 Even wounds that appear to seal adequately at the completion of surgery can actively leak from pressure fluctuations between 5 mm Hg and 110 mm Hg associated with blinking or squeezing of the eyes.5 Such active leaks can lead to low intraocular pressure (IOP) (less than 10 mm Hg), which can result in dynamic changes in the morphology of the wound and enable fluid to enter the anterior chamber.1,2 Accordingly, postoperative day 1 leaks have been
clinically noted corneal edema, and intraocular pressure (IOP) was evaluated.
Results: Ninety eyes of 45 patients were included in the study. One day postoperatively, no wound leak was found in any eye; the sealant was noted to be out of place in 2 (4.4%) of 45 cases. No statistically significant difference was found between sealant and non-sealant eyes in total surgical time (P Z .16) or in IOP (P Z .55), corneal edema (P Z 1.00), or foreign-body sensation (P Z .38) 1 day postoperatively. Conclusion: The hydrogel sealant was not observed to affect duration of surgery or 1-day postoperative IOP, corneal edema, or foreign-body sensation. J Cataract Refract Surg 2017; 43:1010–1014 Q 2017 ASCRS and ESCRS
associated with a 44-fold increase in the risk for endophthalmitis.6 Two widely used options available for sealing CCIs at the end of cataract surgery are sutures and Resure hydrogel ocular sealant (Ocular Therapeutix, Inc.). While use of cyanoacrylate has been studied, it is uncomfortable and toxic to the ocular surface and has not been U.S. Food and Drug Administration (FDA)–approved for closure of CCIs. Fibrin glue, although more comfortable than cyanoacrylate, is more expensive and time-consuming to apply. Some formulations might be of bovine origin, carrying a risk for viral or prion disease transmission or anaphylaxis. Although sutures are thought to be a definitive means for CCI closure, they can induce corneal astigmatism, inflict tissue damage, and cause vacuole formation in the corneal epithelium.7 Furthermore, delayed suture removal can enable introduction of bacteria to the anterior chamber, potentially increasing the risk for endophthalmitis. More important, sutures might not provide as effective a CCI
Submitted: January 24, 2017 | Final revision submitted: April 19, 2017 | Accepted: May 7, 2017 From the Department of Ophthalmology (Nallasamy, Grove, Legault, Daluvoy, Kim), Duke University, Durham, North Carolina, the Orion Eye Center (Grove), Redmond, Oregon, and the San Antonio Military Medical Center (Legault), San Antonio, Texas, USA. Presented in part at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, New Orleans, Louisiana, USA, May 2016. Corresponding author: Terry Kim, MD, Duke University Department of Ophthalmology, 2351 Erwin Road – Box 3802, Durham, North Carolina 27710, USA. E-mail: [email protected]. Q 2017 ASCRS and ESCRS Published by Elsevier Inc.
0886-3350/$ - see frontmatter http://dx.doi.org/10.1016/j.jcrs.2017.05.035
1011
HYDROGEL OCULAR SEALANT FOR CCIS
closure as widely believed. This was indicated by a study showing that 23.8% of sutured CCIs leaked with application of 1.0 ounce of force (0.28 N).8 A recent study comparing the efficacy of sutures and a hydrogel sealant in the closure of CCIs showed that 34.1% of eyes in the suture group had wound leakage with provocation compared with 4.1% in the hydrogel sealant group.4 The eventual sloughing of hydrogel sealant as the wound reepithelializes obviates the need to remove sutures at a postoperative visit. This raises the possibility of expanding the range of cases in which a sealing tool is used. Although the adverse-effect profile of the hydrogel ocular sealant appeared to compare favorably with that of sutures in the pivotal trial,4 using a sealant in cases that otherwise would not use sutures would likely require an adverseeffect profile similar to the profile of sealant-free cataract surgery. To our knowledge, this study is the first to compare the characteristics of cataract surgery performed with and without the hydrogel ocular sealant. PATIENTS AND METHODS Study Design A 1:1 matched cohort of exposure-discordant eyes (1 eye receiving the hydrogel sealant, 1 eye not receiving the sealant) of patients having cataract surgery was generated by reviewing all cataract surgeries performed by the same surgeon (T.K.) at an academic medical center (Duke University Eye Center, Durham, North Carolina, USA) between March 18, 2014, and March 19, 2015. The study protocol was reviewed and approved by the Duke University Medical Center Institutional Review Board. Patients having cataract surgery between the specified dates were included for initial evaluation. Patients who had cataract surgery in both eyes and in whom the hydrogel ocular sealant was used to secure the CCI in only 1 eye were included in the study. Patients whose cataract surgery was combined with synechialysis, trabecular microbypass stent (iStent, Glaukos Corp.) placement, or unplanned anterior vitrectomy were included. Patients were excluded if cataract surgery in either eye had been performed as a combined procedure with vitreoretinal surgery, filtering and aqueous tube shunt surgery, or keratoplasty (penetrating or lamellar). Patients were excluded from the cohort if both of their eyes received ocular sealant during cataract surgery. Data gathered included age; sex; type of IOL; use of suture; presence of wound leak at completion of surgery; duration of surgery; and 1-day postoperative presence of wound leak, presence of ocular sealant on the wound, patient report of foreign-body sensation, and IOP. Wound leak 1 day postoperatively was assessed by performing Seidel testing without pressure. Cases were classified as routine or complex; complex cases were those involving a trabecular microbypass stent, trypan blue staining, a pupil expander (Malyugin ring, Microsurgical Technology), iris hooks, a capsular tension ring, posterior synechialysis, use of an ultrasonic chopper (Ultrachopper, Alcon Laboratories, Inc.) because of high nuclear density, unplanned anterior vitrectomy, or sulcus or anterior chamber IOL placement. Hydrogel Ocular Sealant Resure hydrogel ocular sealant was used in patients whose corneal incision(s) exhibited persistent leakage despite stromal hydration. This sealant is currently FDA approved for intraoperative management of CCIs up to 3.5 mm in length. The sealant is composed primarily of polyethylene glycol and water. It includes a small amount of FD&C Blue No. 1 colorant to help the surgeon visualize the sealant intraoperatively. The sealant is approximately 90% water after polymerization on the ocular surface. The
colorant diffuses out of the bandage within hours of application, with the remaining sealant forming a clear barrier over the CCI. The hydrogel sloughs off in the tear film as the wound reepithelializes, obviating the need to remove the device. Application Technique In eyes that received the sealant, the incisions were dried thoroughly with a cellulose sponge. Wounds were checked to ensure there was no active leakage during application. The hydrogel sealant was prepared by placing 2 drops of buffered salt solution on the trilysine and FD&C Blue well. This was then mixed with the polyethylene glycol to create a liquid form of the sealant. The liquid sealant was applied in a controlled manner to the surface of the incision with a nonabsorbent foam applicator tip. Within 20 seconds of mixing, the sealant polymerized, forming an adherent gel on the ocular surface (Figure 1). Patient Examinations All patients were examined 1 day postoperatively. An ocular review of symptoms was performed, including questions about the presence or absence of foreign-body sensation in the operative eye. Seidel testing of CCIs was performed using Bioglo 1 mg fluorescein strips (Accutome, Inc.). Intraocular pressure was measured using a Tono-Pen XL tonometer (Reichert Technologies). All patients with any visible stromal or epithelial edema on the postoperative day 1 slitlamp examination were designated as having corneal edema. Statistical Analysis Summary statistics of the demographics of the cohort, including age and sex, were computed. The Fisher exact test was used to assess the relationship between hydrogel sealant and case complexity, as well as the binary outcomes of foreign-body sensation and clinically noted corneal edema on postoperative day 1. Because of the non-Gaussian distributions of IOP and surgical time, the Wilcoxon rank-sum test was used to evaluate the effects of use of hydrogel sealant on these measures. Subgroup analyses were performed for each outcome measure to assess for associations independent of case complexity.
RESULTS Baseline Demographic Characteristics
A total of 131 eyes having cataract surgery during the study period received the hydrogel ocular sealant. Ninety eyes of 45 patients who had cataract extraction in each eye with hydrogel ocular sealant used in only 1 eye were included in the study based on the inclusion and exclusion criteria. The mean age of the patients was 67.2 G 11.2 (range 42.0 to 87.0). There was no statistically significant sex predominance in the study population (20 men [44.4%] and 25 women [55.6%]; P Z .55). Operative Characteristics
In all 90 cases, no wound leak was found 1 day postoperatively. The hydrogel ocular sealant was displaced in 2 (4.4%) of 45 cases. Table 1 shows the reasons for complex case designation. Figure 2 shows the specific characteristics leading to the complex case designation in each of the 13 complex cases. Table 2 shows the surgical characteristics and 1day postoperative outcomes; no wound leak was found in any eye. A significantly larger proportion of cases involving hydrogel ocular sealant use were designated as complex than those not involving hydrogel ocular sealant (13 cases Volume 43 Issue 8 August 2017
1012
HYDROGEL OCULAR SEALANT FOR CCIS
Table 1. Reasons for a designation of complex case. Case Feature Ultrasonic chopper use Iridodialysis Trypan blue Pupil expander Synechialysis Trabecular microbypass stent Capsular tension ring Capsule retractors
Figure 1. Appearance of the hydrogel ocular sealant in place on a CCI after staining with fluorescein viewed under (A) diffuse illumination and (B) slit-beam illumination.
[28.9%] versus 1 case [2.0%]) (P ! .001; odds ratio [OR], 17.89; 95% confidence interval [CI], 2.22-143.70). The difference in duration of surgery (minutes) between sealant cases and non-sealant cases was not statistically significant (P Z .16). Analysis of the complex and routine subgroups showed no statistically significant difference in case duration between sealant eyes and non-sealant eyes (P Z .29 and P Z .81, respectively). The median total surgery duration was 16.0 minutes in sealant cases and 16.5 minutes in non-sealant cases. One day postoperatively, there was no statistically significant difference in IOP (mm Hg) between sealant eyes and non-sealant eyes (P Z .55). There was also no statistically significant difference in the odds of clinically noted corneal edema (P Z 1.00; OR, 1.00; 95% CI, 0.34-2.95) or in the rate of foreign-body sensation (P Z 0.25; OR, 2.00; 95% CI, 0.61-6.52) between sealant eyes and non-sealant eyes. DISCUSSION The secure sealing of CCIs is paramount for the prevention of postoperative endophthalmitis in anterior segment intraocular surgery. While suturing of CCIs has been the standard method of closing CCIs that show insufficient evidence of self-sealing, the introduction of a hydrogel ocular sealant offers an additional option for CCI closure. The trend toward comanagement of cataract surgery patients has enabled patients to return to their primary eye care providers more rapidly after surgery and led to a
Figure 2. Specific characteristics leading to the complex case designation in the sealant and non-sealant cases.
Volume 43 Issue 8 August 2017
Cases* (n) 2 1 8 6 1 2 2 1
*A single case might have more than 1 feature qualifying it as a complex case. Thus, the sum of the number of cases is greater than the total number of complex cases in the study.
decline in postoperative evaluations by surgeons of patients with CCIs. Using a suture for CCI closure intraoperatively can create the need for a postoperative visit with a surgeon for suture removal that would otherwise not occur. The availability of a hydrogel ocular sealant that sloughs off during wound reepithelialization obviates the need for additional postoperative visits. Given the potential for large shifts in IOP to occur during blinking, as well as changes in wound morphology, the sealing of CCIs to avoid egress or ingress of fluid is particularly important in cases involving IOLs that require precise positioning, such as multifocal, accommodating, and toric IOLs. In such cases, it is also desirable to avoid suturing a CCI to avoid potential shallowing of the anterior chamber and IOL shift. Although studies have shown the efficacy of the Resure hydrogel ocular sealant in closing CCIs, no study to date has compared the surgical characteristics of cases using this sealant with those in matched control eyes not using the sealant. The current study aimed to elucidate the effects of hydrogel ocular sealant use on routine and complex cataract surgery. To do so, a 1:1 matched cohort of exposure-discordant eyes was generated from surgeries performed by a single surgeon at an academic medical center over a 1-year period. The patients were retrospectively identified to have received the hydrogel ocular sealant for wound closure in only 1 eye during cataract surgery. The identification of this cohort offered an internally matched control eye for each eye that received the hydrogel ocular sealant. As expected, a statistically larger proportion of eyes receiving the sealant were considered complex cases than those not receiving the sealant. Therefore, subgroup analysis was performed to control for the potential effects of procedure complexity on the surgical characteristics evaluated. Despite the tendency toward greater case complexity among eyes that received the hydrogel ocular sealant, no statistically significant difference in total surgical time was found when considering all cases. Furthermore, the median surgical times in routine cases of 16.0 minutes (sealant) and 16.5 minutes (no sealant) argues against the notion that sealant application might increase surgical time. Despite the time required to apply the sealant, effective closure of a wound with the hydrogel ocular sealant might limit the
1013
HYDROGEL OCULAR SEALANT FOR CCIS
Table 2. Surgical characteristics and 1-day postoperative results in sealant eyes and non-sealant eyes. Measure Surgical Laterality, n (%) Right eye Left eye Complex cases, n (%) Total surgical time (min) All cases Median IQR Range Complex cases Median IQR Range Routine cases Median IQR Range 1 day postop IOP (mm Hg) All cases Mean G SD Range Complex cases Mean G SD Range Routine cases Mean G SD Range Corneal edema, n (%) All cases Complex cases Routine cases Foreign-body sensation, n (%) All cases Complex cases Routine cases
Sealant Eyes (n Z 45)
Non-sealant Eyes (n Z 45)
P Value
23 (51.1) 22 (48.9) 13 (28.9)
22 (48.9) 23 (51.1) 1 (2.0)
.99 .99 !.001
19.0 8.0 7.0, 55.0
16.0 7.0 8.0, 68.0
25.0 14.0 15.0, 55.0
16.0 0.0 16.0, 16.0
16.0 6.0 7.0, 26.0
16.5 7.0 8.0, 68.0
21.0 G 6.3 12, 42
22.3 G 8.1 12, 49
23.3 G 8.0 12, 42
26.0 G 0.0 26, 26
20.0 G 5.2 12, 32
22.2 G 8.1 12, 49
8 (17.8) 3 (23.1) 5 (15.6)
8 (17.8) 0 8 (18.2)
.99 .99 .99
9 (20.0) 2 (15.0) 7 (22.0)
5 (11.0) 0 5 (11.0)
.38 .99 .34
.16
.29
.81
.55 .86
.35
IOP Z intraocular pressure; IQR Z interquartile range
time spent performing stromal hydration and drying wounds to observe for leaks. One day postoperatively, the sealant was displaced in 2 of the 45 sealant eyes. Earlier studies indicate that the hydrogel ocular sealant adheres to deepithelialized tissue and is cleared quickly from epithelialized areas. In their 2010 study, Calladine et al.9 noted that 4 of 22 wounds receiving Resure had no sealant present 1 day postoperatively, and that duration of adherence was correlated with the degree of epithelial damage. Accordingly, the cases in the current study in which sealant was displaced might represent eyes in which epithelial damage surrounding the wound was minimal. One day postoperatively, there was no statistically significant difference between sealant eyes and non-sealant eyes in IOP, corneal edema, or foreign-body sensation. Although foreign-body sensation is a highly subjective measure and was evaluated on a binary scale because of the retrospective nature of this study, it did not appear to be an issue in eyes receiving the hydrogel sealant. The 1day postoperative evaluation of foreign-body sensation would likely have been better with a multilevel grading
system, but in the current study it benefited from the presence of an internal control in the form of the patient’s fellow eye. Furthermore, no eye in this study received a bandage contact lens, indicating that the hydrogel sealant did not require additional means to achieve patient comfort. The findings indicate that the Resure hydrogel ocular sealant did not significantly alter surgical characteristics or patient symptomatology when used in routine or complex cataract surgeries. The findings are relevant for surgeons concerned with surgical efficiency and also indicate that patient counseling about sealant use for wound closure might not be warranted. The absence of significant changes in surgical characteristics or patient symptomatology raises the option of routinely using the hydrogel ocular sealant in eyes receiving multifocal, accommodating, or toric IOLs, for which stable positioning is paramount. Future directions for this work might involve evaluation of postoperative corneal edema in the absence of stromal hydration with the use of a hydrogel sealant as well as fine-grained analysis of foreign-body sensation using a multilevel grading system.
Volume 43 Issue 8 August 2017
1014
HYDROGEL OCULAR SEALANT FOR CCIS
WHAT WAS KNOWN The hydrogel ocular sealant offers a safe and effective alternative to sutures for the closure of CCIs.
5. 6.
WHAT THIS PAPER ADDS Hydrogel ocular sealant use during cataract surgery was not associated with a change in surgery duration, IOP, corneal edema, or foreign-body sensation when compared with fellow eyes having the same procedure without the hydrogel ocular sealant.
7.
8.
9.
REFERENCES 1. Taban M, Rao B, Reznik J, Zhang J, Chen Z, McDonnell PJ. Dynamic morphology of sutureless cataract wounds – effect of incision angle and location. Surv Ophthalmol 2004; 49 (suppl 2):S62–S72 2. Taban M, Sarayba MA, Ignacio TS, Behrens A, McDonnell PJ. Ingress of India ink into the anterior chamber through sutureless clear corneal cataract wounds. Arch Ophthalmol 2005; 123:643–648. Available at: http://jamanetwork.com/journals/jamaophthalmology /fullarticle/417015. Accessed May 20, 2017 3. Faulkner W. Inflow of ocular surface fluid into the anterior chamber after phacoemulsification through sutureless corneal cataract wounds. [letter]. Am J Ophthalmol 2006; 141:781; reply by S Herretes, WJ Stark, PJ McDonnell, A Behrens, 781–782 4. Masket S, Hovanesian JA, Levenson J, Tyson F, Flynn W, Endl M, Majmudar PA, Modi S, Chu R, Raizman MB, Lane SS, Kim T. Hydrogel
Volume 43 Issue 8 August 2017
sealant versus sutures to prevent fluid egress after cataract surgery. J Cataract Refract Surg 2014; 40:2057–2066 Coleman DJ, Trokel S. Direct-recorded intraocular pressure variations in a human subject. Arch Ophthalmol 1969; 82:637–640 Wallin T, Parker J, Jin Y, Kefalopoulos G, Olson RJ. Cohort study of 27 cases of endophthalmitis at a single institution. J Cataract refract Surg 2005; 31:735–741 Shahbazi J, Marc¸al H, Watson S, Wakefield D, Sarris M, Foster LJR. Sutureless sealing of penetrating corneal wounds using a laser-activated thin film adhesive. Lasers Surg Med 2011; 43:490–498 Masket S, Hovanesian J, Raizman M, Wee D, Fram N. Use of a calibrated force gauge in clear corneal cataract surgery to quantify point-pressure manipulation. J Cataract Refract Surg 2013; 39:511– 518 Calladine D, Ward M, Packard R. Adherent ocular bandage for clear corneal incisions used in cataract surgery. J Cataract Refract Surg 2010; 36:1839–1848
Disclosures: Dr. Kim is a consultant to Ocular Therapeutix, Inc. None of the other authors has a financial or proprietary interest in any material or method mentioned.
First author: Nambi Nallasamy, MD Department of Ophthalmology, Duke University, Durham, North Carolina, USA
ARTICLE
Hydrogel ocular sealant for clear corneal incisions in cataract surgery Nambi Nallasamy, MD, Karen E. Grove, MD, Gary L. Legault, MD, Melissa B. Daluvoy, MD, Terry Kim, MD
Purpose: To assess the relationship between use of a hydrogel ocular sealant (Resure) to secure clear corneal incisions (CCIs) in cataract surgery and surgeon efficiency, patient symptomatology, and postoperative results. Setting: Duke University Eye Center, Durham, North Carolina, USA.
Design: Retrospective case series. Methods: A 1:1 matched cohort of hydrogel sealant exposure– discordant eyes of cataract surgery patients was retrospectively generated. Consecutive patients who had bilateral cataract surgery during the study period and in whom the hydrogel sealant was used to secure the CCI in only 1 of the 2 eyes were included in the study. The relationship between use of the hydrogel sealant and surgical time, 1-day postoperative foreign-body sensation,
T
he transition from scleral to clear corneal incisions (CCIs) for cataract surgery has been facilitated by the development of phacoemulsification and foldable intraocular lenses (IOLs). The CCI is generally intended to be self-sealing, but studies indicate that wound construction has a significant impact on the rate of wound leak at the completion of cataract surgery.1–4 A recent study involving single-plane CCIs for cataract surgery reported a rate of spontaneous wound leak of 48.8% and a rate of wound leak with 1 ounce or less of pressure of 97.6%.4 Even wounds that appear to seal adequately at the completion of surgery can actively leak from pressure fluctuations between 5 mm Hg and 110 mm Hg associated with blinking or squeezing of the eyes.5 Such active leaks can lead to low intraocular pressure (IOP) (less than 10 mm Hg), which can result in dynamic changes in the morphology of the wound and enable fluid to enter the anterior chamber.1,2 Accordingly, postoperative day 1 leaks have been
clinically noted corneal edema, and intraocular pressure (IOP) was evaluated.
Results: Ninety eyes of 45 patients were included in the study. One day postoperatively, no wound leak was found in any eye; the sealant was noted to be out of place in 2 (4.4%) of 45 cases. No statistically significant difference was found between sealant and non-sealant eyes in total surgical time (P Z .16) or in IOP (P Z .55), corneal edema (P Z 1.00), or foreign-body sensation (P Z .38) 1 day postoperatively. Conclusion: The hydrogel sealant was not observed to affect duration of surgery or 1-day postoperative IOP, corneal edema, or foreign-body sensation. J Cataract Refract Surg 2017; 43:1010–1014 Q 2017 ASCRS and ESCRS
associated with a 44-fold increase in the risk for endophthalmitis.6 Two widely used options available for sealing CCIs at the end of cataract surgery are sutures and Resure hydrogel ocular sealant (Ocular Therapeutix, Inc.). While use of cyanoacrylate has been studied, it is uncomfortable and toxic to the ocular surface and has not been U.S. Food and Drug Administration (FDA)–approved for closure of CCIs. Fibrin glue, although more comfortable than cyanoacrylate, is more expensive and time-consuming to apply. Some formulations might be of bovine origin, carrying a risk for viral or prion disease transmission or anaphylaxis. Although sutures are thought to be a definitive means for CCI closure, they can induce corneal astigmatism, inflict tissue damage, and cause vacuole formation in the corneal epithelium.7 Furthermore, delayed suture removal can enable introduction of bacteria to the anterior chamber, potentially increasing the risk for endophthalmitis. More important, sutures might not provide as effective a CCI
Submitted: January 24, 2017 | Final revision submitted: April 19, 2017 | Accepted: May 7, 2017 From the Department of Ophthalmology (Nallasamy, Grove, Legault, Daluvoy, Kim), Duke University, Durham, North Carolina, the Orion Eye Center (Grove), Redmond, Oregon, and the San Antonio Military Medical Center (Legault), San Antonio, Texas, USA. Presented in part at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, New Orleans, Louisiana, USA, May 2016. Corresponding author: Terry Kim, MD, Duke University Department of Ophthalmology, 2351 Erwin Road – Box 3802, Durham, North Carolina 27710, USA. E-mail: [email protected]. Q 2017 ASCRS and ESCRS Published by Elsevier Inc.
0886-3350/$ - see frontmatter http://dx.doi.org/10.1016/j.jcrs.2017.05.035
1011
HYDROGEL OCULAR SEALANT FOR CCIS
closure as widely believed. This was indicated by a study showing that 23.8% of sutured CCIs leaked with application of 1.0 ounce of force (0.28 N).8 A recent study comparing the efficacy of sutures and a hydrogel sealant in the closure of CCIs showed that 34.1% of eyes in the suture group had wound leakage with provocation compared with 4.1% in the hydrogel sealant group.4 The eventual sloughing of hydrogel sealant as the wound reepithelializes obviates the need to remove sutures at a postoperative visit. This raises the possibility of expanding the range of cases in which a sealing tool is used. Although the adverse-effect profile of the hydrogel ocular sealant appeared to compare favorably with that of sutures in the pivotal trial,4 using a sealant in cases that otherwise would not use sutures would likely require an adverseeffect profile similar to the profile of sealant-free cataract surgery. To our knowledge, this study is the first to compare the characteristics of cataract surgery performed with and without the hydrogel ocular sealant. PATIENTS AND METHODS Study Design A 1:1 matched cohort of exposure-discordant eyes (1 eye receiving the hydrogel sealant, 1 eye not receiving the sealant) of patients having cataract surgery was generated by reviewing all cataract surgeries performed by the same surgeon (T.K.) at an academic medical center (Duke University Eye Center, Durham, North Carolina, USA) between March 18, 2014, and March 19, 2015. The study protocol was reviewed and approved by the Duke University Medical Center Institutional Review Board. Patients having cataract surgery between the specified dates were included for initial evaluation. Patients who had cataract surgery in both eyes and in whom the hydrogel ocular sealant was used to secure the CCI in only 1 eye were included in the study. Patients whose cataract surgery was combined with synechialysis, trabecular microbypass stent (iStent, Glaukos Corp.) placement, or unplanned anterior vitrectomy were included. Patients were excluded if cataract surgery in either eye had been performed as a combined procedure with vitreoretinal surgery, filtering and aqueous tube shunt surgery, or keratoplasty (penetrating or lamellar). Patients were excluded from the cohort if both of their eyes received ocular sealant during cataract surgery. Data gathered included age; sex; type of IOL; use of suture; presence of wound leak at completion of surgery; duration of surgery; and 1-day postoperative presence of wound leak, presence of ocular sealant on the wound, patient report of foreign-body sensation, and IOP. Wound leak 1 day postoperatively was assessed by performing Seidel testing without pressure. Cases were classified as routine or complex; complex cases were those involving a trabecular microbypass stent, trypan blue staining, a pupil expander (Malyugin ring, Microsurgical Technology), iris hooks, a capsular tension ring, posterior synechialysis, use of an ultrasonic chopper (Ultrachopper, Alcon Laboratories, Inc.) because of high nuclear density, unplanned anterior vitrectomy, or sulcus or anterior chamber IOL placement. Hydrogel Ocular Sealant Resure hydrogel ocular sealant was used in patients whose corneal incision(s) exhibited persistent leakage despite stromal hydration. This sealant is currently FDA approved for intraoperative management of CCIs up to 3.5 mm in length. The sealant is composed primarily of polyethylene glycol and water. It includes a small amount of FD&C Blue No. 1 colorant to help the surgeon visualize the sealant intraoperatively. The sealant is approximately 90% water after polymerization on the ocular surface. The
colorant diffuses out of the bandage within hours of application, with the remaining sealant forming a clear barrier over the CCI. The hydrogel sloughs off in the tear film as the wound reepithelializes, obviating the need to remove the device. Application Technique In eyes that received the sealant, the incisions were dried thoroughly with a cellulose sponge. Wounds were checked to ensure there was no active leakage during application. The hydrogel sealant was prepared by placing 2 drops of buffered salt solution on the trilysine and FD&C Blue well. This was then mixed with the polyethylene glycol to create a liquid form of the sealant. The liquid sealant was applied in a controlled manner to the surface of the incision with a nonabsorbent foam applicator tip. Within 20 seconds of mixing, the sealant polymerized, forming an adherent gel on the ocular surface (Figure 1). Patient Examinations All patients were examined 1 day postoperatively. An ocular review of symptoms was performed, including questions about the presence or absence of foreign-body sensation in the operative eye. Seidel testing of CCIs was performed using Bioglo 1 mg fluorescein strips (Accutome, Inc.). Intraocular pressure was measured using a Tono-Pen XL tonometer (Reichert Technologies). All patients with any visible stromal or epithelial edema on the postoperative day 1 slitlamp examination were designated as having corneal edema. Statistical Analysis Summary statistics of the demographics of the cohort, including age and sex, were computed. The Fisher exact test was used to assess the relationship between hydrogel sealant and case complexity, as well as the binary outcomes of foreign-body sensation and clinically noted corneal edema on postoperative day 1. Because of the non-Gaussian distributions of IOP and surgical time, the Wilcoxon rank-sum test was used to evaluate the effects of use of hydrogel sealant on these measures. Subgroup analyses were performed for each outcome measure to assess for associations independent of case complexity.
RESULTS Baseline Demographic Characteristics
A total of 131 eyes having cataract surgery during the study period received the hydrogel ocular sealant. Ninety eyes of 45 patients who had cataract extraction in each eye with hydrogel ocular sealant used in only 1 eye were included in the study based on the inclusion and exclusion criteria. The mean age of the patients was 67.2 G 11.2 (range 42.0 to 87.0). There was no statistically significant sex predominance in the study population (20 men [44.4%] and 25 women [55.6%]; P Z .55). Operative Characteristics
In all 90 cases, no wound leak was found 1 day postoperatively. The hydrogel ocular sealant was displaced in 2 (4.4%) of 45 cases. Table 1 shows the reasons for complex case designation. Figure 2 shows the specific characteristics leading to the complex case designation in each of the 13 complex cases. Table 2 shows the surgical characteristics and 1day postoperative outcomes; no wound leak was found in any eye. A significantly larger proportion of cases involving hydrogel ocular sealant use were designated as complex than those not involving hydrogel ocular sealant (13 cases Volume 43 Issue 8 August 2017
1012
HYDROGEL OCULAR SEALANT FOR CCIS
Table 1. Reasons for a designation of complex case. Case Feature Ultrasonic chopper use Iridodialysis Trypan blue Pupil expander Synechialysis Trabecular microbypass stent Capsular tension ring Capsule retractors
Figure 1. Appearance of the hydrogel ocular sealant in place on a CCI after staining with fluorescein viewed under (A) diffuse illumination and (B) slit-beam illumination.
[28.9%] versus 1 case [2.0%]) (P ! .001; odds ratio [OR], 17.89; 95% confidence interval [CI], 2.22-143.70). The difference in duration of surgery (minutes) between sealant cases and non-sealant cases was not statistically significant (P Z .16). Analysis of the complex and routine subgroups showed no statistically significant difference in case duration between sealant eyes and non-sealant eyes (P Z .29 and P Z .81, respectively). The median total surgery duration was 16.0 minutes in sealant cases and 16.5 minutes in non-sealant cases. One day postoperatively, there was no statistically significant difference in IOP (mm Hg) between sealant eyes and non-sealant eyes (P Z .55). There was also no statistically significant difference in the odds of clinically noted corneal edema (P Z 1.00; OR, 1.00; 95% CI, 0.34-2.95) or in the rate of foreign-body sensation (P Z 0.25; OR, 2.00; 95% CI, 0.61-6.52) between sealant eyes and non-sealant eyes. DISCUSSION The secure sealing of CCIs is paramount for the prevention of postoperative endophthalmitis in anterior segment intraocular surgery. While suturing of CCIs has been the standard method of closing CCIs that show insufficient evidence of self-sealing, the introduction of a hydrogel ocular sealant offers an additional option for CCI closure. The trend toward comanagement of cataract surgery patients has enabled patients to return to their primary eye care providers more rapidly after surgery and led to a
Figure 2. Specific characteristics leading to the complex case designation in the sealant and non-sealant cases.
Volume 43 Issue 8 August 2017
Cases* (n) 2 1 8 6 1 2 2 1
*A single case might have more than 1 feature qualifying it as a complex case. Thus, the sum of the number of cases is greater than the total number of complex cases in the study.
decline in postoperative evaluations by surgeons of patients with CCIs. Using a suture for CCI closure intraoperatively can create the need for a postoperative visit with a surgeon for suture removal that would otherwise not occur. The availability of a hydrogel ocular sealant that sloughs off during wound reepithelialization obviates the need for additional postoperative visits. Given the potential for large shifts in IOP to occur during blinking, as well as changes in wound morphology, the sealing of CCIs to avoid egress or ingress of fluid is particularly important in cases involving IOLs that require precise positioning, such as multifocal, accommodating, and toric IOLs. In such cases, it is also desirable to avoid suturing a CCI to avoid potential shallowing of the anterior chamber and IOL shift. Although studies have shown the efficacy of the Resure hydrogel ocular sealant in closing CCIs, no study to date has compared the surgical characteristics of cases using this sealant with those in matched control eyes not using the sealant. The current study aimed to elucidate the effects of hydrogel ocular sealant use on routine and complex cataract surgery. To do so, a 1:1 matched cohort of exposure-discordant eyes was generated from surgeries performed by a single surgeon at an academic medical center over a 1-year period. The patients were retrospectively identified to have received the hydrogel ocular sealant for wound closure in only 1 eye during cataract surgery. The identification of this cohort offered an internally matched control eye for each eye that received the hydrogel ocular sealant. As expected, a statistically larger proportion of eyes receiving the sealant were considered complex cases than those not receiving the sealant. Therefore, subgroup analysis was performed to control for the potential effects of procedure complexity on the surgical characteristics evaluated. Despite the tendency toward greater case complexity among eyes that received the hydrogel ocular sealant, no statistically significant difference in total surgical time was found when considering all cases. Furthermore, the median surgical times in routine cases of 16.0 minutes (sealant) and 16.5 minutes (no sealant) argues against the notion that sealant application might increase surgical time. Despite the time required to apply the sealant, effective closure of a wound with the hydrogel ocular sealant might limit the
1013
HYDROGEL OCULAR SEALANT FOR CCIS
Table 2. Surgical characteristics and 1-day postoperative results in sealant eyes and non-sealant eyes. Measure Surgical Laterality, n (%) Right eye Left eye Complex cases, n (%) Total surgical time (min) All cases Median IQR Range Complex cases Median IQR Range Routine cases Median IQR Range 1 day postop IOP (mm Hg) All cases Mean G SD Range Complex cases Mean G SD Range Routine cases Mean G SD Range Corneal edema, n (%) All cases Complex cases Routine cases Foreign-body sensation, n (%) All cases Complex cases Routine cases
Sealant Eyes (n Z 45)
Non-sealant Eyes (n Z 45)
P Value
23 (51.1) 22 (48.9) 13 (28.9)
22 (48.9) 23 (51.1) 1 (2.0)
.99 .99 !.001
19.0 8.0 7.0, 55.0
16.0 7.0 8.0, 68.0
25.0 14.0 15.0, 55.0
16.0 0.0 16.0, 16.0
16.0 6.0 7.0, 26.0
16.5 7.0 8.0, 68.0
21.0 G 6.3 12, 42
22.3 G 8.1 12, 49
23.3 G 8.0 12, 42
26.0 G 0.0 26, 26
20.0 G 5.2 12, 32
22.2 G 8.1 12, 49
8 (17.8) 3 (23.1) 5 (15.6)
8 (17.8) 0 8 (18.2)
.99 .99 .99
9 (20.0) 2 (15.0) 7 (22.0)
5 (11.0) 0 5 (11.0)
.38 .99 .34
.16
.29
.81
.55 .86
.35
IOP Z intraocular pressure; IQR Z interquartile range
time spent performing stromal hydration and drying wounds to observe for leaks. One day postoperatively, the sealant was displaced in 2 of the 45 sealant eyes. Earlier studies indicate that the hydrogel ocular sealant adheres to deepithelialized tissue and is cleared quickly from epithelialized areas. In their 2010 study, Calladine et al.9 noted that 4 of 22 wounds receiving Resure had no sealant present 1 day postoperatively, and that duration of adherence was correlated with the degree of epithelial damage. Accordingly, the cases in the current study in which sealant was displaced might represent eyes in which epithelial damage surrounding the wound was minimal. One day postoperatively, there was no statistically significant difference between sealant eyes and non-sealant eyes in IOP, corneal edema, or foreign-body sensation. Although foreign-body sensation is a highly subjective measure and was evaluated on a binary scale because of the retrospective nature of this study, it did not appear to be an issue in eyes receiving the hydrogel sealant. The 1day postoperative evaluation of foreign-body sensation would likely have been better with a multilevel grading
system, but in the current study it benefited from the presence of an internal control in the form of the patient’s fellow eye. Furthermore, no eye in this study received a bandage contact lens, indicating that the hydrogel sealant did not require additional means to achieve patient comfort. The findings indicate that the Resure hydrogel ocular sealant did not significantly alter surgical characteristics or patient symptomatology when used in routine or complex cataract surgeries. The findings are relevant for surgeons concerned with surgical efficiency and also indicate that patient counseling about sealant use for wound closure might not be warranted. The absence of significant changes in surgical characteristics or patient symptomatology raises the option of routinely using the hydrogel ocular sealant in eyes receiving multifocal, accommodating, or toric IOLs, for which stable positioning is paramount. Future directions for this work might involve evaluation of postoperative corneal edema in the absence of stromal hydration with the use of a hydrogel sealant as well as fine-grained analysis of foreign-body sensation using a multilevel grading system.
Volume 43 Issue 8 August 2017
1014
HYDROGEL OCULAR SEALANT FOR CCIS
WHAT WAS KNOWN The hydrogel ocular sealant offers a safe and effective alternative to sutures for the closure of CCIs.
5. 6.
WHAT THIS PAPER ADDS Hydrogel ocular sealant use during cataract surgery was not associated with a change in surgery duration, IOP, corneal edema, or foreign-body sensation when compared with fellow eyes having the same procedure without the hydrogel ocular sealant.
7.
8.
9.
REFERENCES 1. Taban M, Rao B, Reznik J, Zhang J, Chen Z, McDonnell PJ. Dynamic morphology of sutureless cataract wounds – effect of incision angle and location. Surv Ophthalmol 2004; 49 (suppl 2):S62–S72 2. Taban M, Sarayba MA, Ignacio TS, Behrens A, McDonnell PJ. Ingress of India ink into the anterior chamber through sutureless clear corneal cataract wounds. Arch Ophthalmol 2005; 123:643–648. Available at: http://jamanetwork.com/journals/jamaophthalmology /fullarticle/417015. Accessed May 20, 2017 3. Faulkner W. Inflow of ocular surface fluid into the anterior chamber after phacoemulsification through sutureless corneal cataract wounds. [letter]. Am J Ophthalmol 2006; 141:781; reply by S Herretes, WJ Stark, PJ McDonnell, A Behrens, 781–782 4. Masket S, Hovanesian JA, Levenson J, Tyson F, Flynn W, Endl M, Majmudar PA, Modi S, Chu R, Raizman MB, Lane SS, Kim T. Hydrogel
Volume 43 Issue 8 August 2017
sealant versus sutures to prevent fluid egress after cataract surgery. J Cataract Refract Surg 2014; 40:2057–2066 Coleman DJ, Trokel S. Direct-recorded intraocular pressure variations in a human subject. Arch Ophthalmol 1969; 82:637–640 Wallin T, Parker J, Jin Y, Kefalopoulos G, Olson RJ. Cohort study of 27 cases of endophthalmitis at a single institution. J Cataract refract Surg 2005; 31:735–741 Shahbazi J, Marc¸al H, Watson S, Wakefield D, Sarris M, Foster LJR. Sutureless sealing of penetrating corneal wounds using a laser-activated thin film adhesive. Lasers Surg Med 2011; 43:490–498 Masket S, Hovanesian J, Raizman M, Wee D, Fram N. Use of a calibrated force gauge in clear corneal cataract surgery to quantify point-pressure manipulation. J Cataract Refract Surg 2013; 39:511– 518 Calladine D, Ward M, Packard R. Adherent ocular bandage for clear corneal incisions used in cataract surgery. J Cataract Refract Surg 2010; 36:1839–1848
Disclosures: Dr. Kim is a consultant to Ocular Therapeutix, Inc. None of the other authors has a financial or proprietary interest in any material or method mentioned.
First author: Nambi Nallasamy, MD Department of Ophthalmology, Duke University, Durham, North Carolina, USA
