|Year : 2020 | Volume
| Issue : 4 | Page : 229-235
Evaluation of the efficacy of autologous cryoprecipitate for attaching conjunctival autograft after primary pterygium excision
Hazem E Haroun1, Ahmed M Hassan2, Safaa A Aboud1
1 Department of Ophthalmology, Beni-Suef University, Beni-Suef, Egypt
2 National Eye Center of Ophthalmology, Rod El Farag, Egypt
|Date of Submission||19-Apr-2020|
|Date of Decision||02-Jun-2020|
|Date of Acceptance||24-Jul-2020|
|Date of Web Publication||28-Dec-2020|
MD Safaa A Aboud
Department of Ophthalmology, Beni-Suef University, 23 Namek Street, Moold Elnaby Square, Beni-Suef 62511
Source of Support: None, Conflict of Interest: None
Purpose The aim of this study was to evaluate the long-term safety and efficacy of using autologous cryoprecipitate for attaching conjunctival autograft and to compare the results of such technique with the use of vicryl sutures in patients undergoing primary pterygium excision, in terms of surgical time, postoperative patient comfort, visual acuity, complications, and recurrence rate.
Patients and methods This is a prospective, interventional, comparative clinical study. It included 200 patients with primary nasal pterygium for whom surgical excision of the pterygium with conjunctival autograft obtained from the same eye was performed. The patients were divided into two groups: autologous cryoprecipitate was used in 100 patients (glue group) and absorbable sutures (8/0 vicryl sutures) were used in 100 patients (suture group) to attach the free conjunctival graft. The main outcome measures included operative time, postoperative pain, lacrimation, foreign body sensation, recurrence rate, and complications. The follow-up period was 24 months.
Results The mean operative time was 20.28±2.73 min in the glue group and 31.04±6.52 min in the suture group, with a statistically significant difference (P<0.05). At the first postoperative day, pain, foreign body sensation, and lacrimation were reported by all patients in the suture group, whereas in the glue group, pain was reported in all patients, foreign body sensation was reported in 40 patients, and lacrimation was reported in 70 patients, with a statistically significant difference between the two groups (P<0.001). Pain and foreign body sensation persisted beyond the first week in 44 patients in the suture group and in only five patients in the glue group, with a statistically significant difference (P<0.001). Postoperative subconjunctival hemorrhage was reported in five patients in the glue group and in 15 patients in the suture group, with a statistically significant difference (P<0.05). Recurrence occurred in three patients in the glue group and in 12 patients in the suture group, which was statistically significantly lower in the glue group (P<0.05).
Conclusion Using autologous cryoprecipitate for attaching conjunctival autograft in primary pterygium surgery resulted in shorter operative time and less postoperative pain, foreign body sensation, lacrimation, and subconjunctival hemorrhage. In addition, it decreased the recurrence rate. The cryoprecipitate method appeared to be effective, reliable, and safe after long-term follow-up.
Keywords: autologous cryoprecipitate, conjunctival autograft, primary pterygium excision
|How to cite this article:|
Haroun HE, Hassan AM, Aboud SA. Evaluation of the efficacy of autologous cryoprecipitate for attaching conjunctival autograft after primary pterygium excision. Delta J Ophthalmol 2020;21:229-35
|How to cite this URL:|
Haroun HE, Hassan AM, Aboud SA. Evaluation of the efficacy of autologous cryoprecipitate for attaching conjunctival autograft after primary pterygium excision. Delta J Ophthalmol [serial online] 2020 [cited 2022 Jul 3];21:229-35. Available from: http://www.djo.eg.net/text.asp?2020/21/4/229/304940
| Introduction|| |
Pterygium is a wing-shaped conjunctival encroachment onto the cornea. It is more frequent in areas with more ultraviolet radiation and in hot, windy, dusty, dry, and smoky environments. Ultraviolet light-induced destruction of the limbal stem cell barrier with subsequent subjunctivization of the cornea is the currently accepted etiology . In the advanced stage, it is a potentially blinding disease where it encroaches on the visual axis and requires surgery for visual rehabilitation .
Various surgical procedures are available to treat this condition, with the prevention of recurrence as the primary goal. The use of a conjunctival graft to cover the bare sclera after excision of the pterygium is the most effective method of decreasing the recurrence rate and is based on the theory of restoring the anatomical integrity of the limbus and addressing limbal stem cell deficiency . Patient comfort for the first few days after surgery is an important factor in this type of intervention. The autograft is anchored to the scleral bed with sutures or through tissue glues or autologous serum .
The most common method of autograft fixation is using sutures. Suturing requires surgical experience and technical skills. An ideal suture is one that is non-allergenic, easy to handle, does not promote infection, and is affordable. None of the currently available sutures fulfill the criteria of an ideal suture . Sutures may cause conjunctival inflammation and Langerhans cell migration into the cornea . Additionally, using sutures has its drawbacks, such as increased operating time and postoperative discomfort, pain, lacrimation, inflammation, necrosis, buttonholes, giant papillary conjunctivitis, scarring, dellen, symblepharon, and granuloma formation. With the invention of newer alternatives, such as fibrin glue and autologous blood, suture-related complications have come to a halt .
The tissue adhesive glue is a two-component structure (fibrinogen and thrombin), which mimics natural fibrin formation. It is prepared from banked human blood and is commercially available . It has the advantages of easy fixation of the graft, shorter operative time, reduction in complications, and postoperative discomfort. The risk of transmission of prion disease and anaphylaxis in susceptible individuals are the main limiting factors of its use. Other disadvantages include high cost, lack of availability, and its biological origin that carries risk of postoperative inflammation, in addition to inactivation by iodine preparations .
Another approach is the use of autologous blood for graft fixation. Autologous blood is natural, has no extra cost or associated risks and can prevent postoperative irritation . However, this is a technically difficult approach . Subconjunctival hemorrhage is a common finding with its use, as blood is used for graft fixation. Graft retraction and graft loss are more common with autologous blood, which could be owing to the weak adhesive property of autologous blood in comparison with the commercially available fibrin glue preparation .
Autologous cryoprecipitate (fibrin adhesive) is a derivative of the blood product that imitates the last cascade of blood clotting. It consists of two components: tissue adhesion proteins (fibrinogen, coagulation factor 13, and aprotinin) and thrombin, in addition to solutions, which are paired before the operative procedure .
The aim of this study was to evaluate the long-term safety and efficacy of using autologous cryoprecipitate for attaching conjunctival autograft in primary pterygium surgery.
| Patients and methods|| |
The study was approved by the Ethical Committee of Scientific Research, Faculty of Medicine, Beni-Suef University, before starting data collection. Patients were given full explanations about the purpose of the study, with confirmation regarding the confidentiality of data. Informed consent was signed by all patients to participate in the study and for publication of data before being enrolled in the study.
This study was conducted on 200 patients with primary nasal pterygium in the period from August 2017 to February 2020. The patients were recruited from the Ophthalmology Outpatient Clinic, Beni-Suef University Hospital. They were divided into two groups: glue group and suture group. The glue group included 100 patients who were managed by pterygium excision with free conjunctival autograft using autologous cryoprecipitate to attach the autograft to the sclera. The suture group included 100 patients who were managed by pterygium excision with free conjunctival autograft using absorbable 8/0 vicryl sutures to attach the autograft to the sclera. The patients in both groups were similar with respect to the exposure to occupational and environmental risk factors for pterygium occurrence and recurrence.
The study inclusion criteria were as follows: age between 18 and 80 years, patients with primary nasal pterygium who were indicated for surgery owing to cosmesis, foreign body sensation, recurrent inflammation, visual impairment, diplopia from motility restriction, and difficulty in wearing contact lenses. The exclusion criteria were patients unsuitable for a follow-up period of at least 24 months after surgery, the presence of symblepharon, significant ocular surface disease, ocular pathology like glaucoma or uveitis, recurrent or atrophic pterygium, bleeding or coagulation disorders, or patients on anticoagulants or antiplatelet treatment and hypersensitivity to any component of fibrin.
Preoperatively, all patients were subjected to detailed history taking, full ophthalmological examination, including visual acuity, both uncorrected visual acuity and best-corrected visual acuity (BCVA) using an autorefractometer and Landolt’s broken ring chart with visual acuity expressed in decimal units, slit-lamp biomicroscopy, intraocular pressure measurement, fundus examination, and ocular motility examination.
Preparation of the glue material
- Preparation of autologous cryoprecipitate: cryoprecipitate is a concentrate of high-molecular-weight plasma proteins that precipitates when frozen plasma is slowly thawed at 1–6°C. In brief, fibrinogen adhesive was prepared from each patient by obtaining 15 ml of blood into a syringe containing 5 ml of 3.8% w/v sodium citrate. The blood was centrifuged, and the plasma was separated, frozen to −20°C, and then was allowed to thaw to 4°C overnight. The precipitated fibrinogen was separated by further centrifugation at 4°C, and the supernatant serum was removed. The cryoprecipitate was then refrozen to −20°C and stored for up to 48 h . It was prepared by the technicians in the hospital laboratory.
- Preparation of synthetic thrombin: it is commercially available (LABiTec PT-R) (LABiTec GmbH, Ahrensburg, Germany).
A single surgeon performed all surgeries (SAA). With standard ophthalmologic sterile preparation, the eye was exposed using a lid speculum, and surface anesthesia in the form of Benox eye drops (benoxinate hydrochloride 0.4%; E.I.P.I.CO, Cairo, Egypt) was used. The surgery was performed under an operating microscope. The horizontal size of the pterygium was measured (the corneal area encroached in millimeters from the limbus) using a caliper to record the grading of the pterygium: grade I: wingy-shaped fibrovascular growth of the conjunctiva that extends less than 2 mm onto the cornea, grade II: wingy-shaped fibrovascular growth of the conjunctiva that involves up to 4 mm of the cornea, and grade III: wingy-shaped fibrovascular growth of the conjunctiva that encroaches onto more than 4 mm of the cornea and involves the visual axis . Lidocaine HCL 20 mg/ml (Debocaine 2%; The Arab Company, Obour City, Egypt) was injected into the pterygium body to balloon out the conjunctiva. The pterygium head was separated from the cornea by blunt and sharp dissection, and the conjunctiva with the underlying Tenon’s capsule was excised. The wound bed was scraped to bare sclera and minimal Ringer-lactate solution (EIPICO, Borg Elarab City, Egypt), with added adrenaline was used for irrigation, and bleeding vessels were not cauterized. The dimensions of the bare scleral bed were measured with a caliper and a free graft, with an additional 1.0 mm length and width was then obtained from the superior temporal bulbar conjunctiva with care to obtain a Tenon-free graft. The limbal edge of the graft contained a thin rim of corneal epithelium. The graft was thereafter moved to the nasal area and attached to the sclera with either autologous cryoprecipitate (glue group) or by using absorbable 8/0 vicryl sutures (suture group). Proper orientation was maintained, with the epithelial side facing upward and the limbal edge toward the limbus. The donor site was left to epithelialize without closure of the defect.
In the glue group, one drop of the autologous cryoprecipitate was placed on the scleral bed and then one drop of the thrombin component was applied to activate the sealant. The graft was quickly flipped over the sclera with care taken to maintain the proper orientation. The fibrinogen was activated by the thrombin, forming a fibrin clot with sufficient adhesive power (fibrin glue). Approximately 30 s was allowed to smooth out the graft and depress it gently to the scleral bed. Any excess glue was removed, and the graft was trimmed if necessary. After a drying period of 1 min, the lid speculum was removed. The glue does not stick to the intact corneal or conjunctival epithelium. None of the glue patients required suturing ([Figure 1]).
In the suture group, 8/0 vicryl sutures (2006, J574, P30; Ethicon Inc., 655 Ethicon Cir, Cornelia, GA, United States) were used where the four corners of the graft and the central nasal edge were anchored to the conjunctiva and knots were buried whenever possible ([Figure 2]). The operative time was recorded in all patients.
|Figure 2 Suture group. (a) before surgery and (b) at the end of surgery.|
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Postoperatively, the operated eye was bandaged with a double eye patch for at least 24 h. The patients were treated with Tobradex eye drops (tobramycin 0.3% and dexamethasone 0.1%, Novartis, Canada), four times daily for two weeks. This was followed by a tapering dose over the next four weeks. Pharma Tears eye drops (carboxymethyl cellulose 0.5%; Pharma Medica, Nasr city, Cairo, Egypt) were used four times daily for 6 weeks. Postoperative medications were started on the first postoperative day.
Follow-up was done on the first day after surgery and then after 1 week to examine the corneal re-epithelialization and graft characteristics such as stability, inflammation, and edema. Subsequent follow-up was done at first, third, sixth, 12th, 18th, and 24th months after surgery. The subjective symptoms of patients including postoperative pain, foreign body sensation, and lacrimation were questioned at every follow-up visit, and the occurrence of complications, including subconjunctival hemorrhage, graft edema or failure, granuloma, and recurrence (defined as any growth of fibrovascular tissue onto the cornea during the entire follow-up period) were reported. BCVA and astigmatism were measured at each visit.
Recurrence of pterygia was monitored based on an operation site grading system as previously proposed; grades 1 to 3 were considered as no recurrence and grade 4 was considered a recurrence. Grade 1 represented normal appearance of the operated site, grade 2 represented the presence of fine episcleral vessels in the excised area extending to the limbus but without any fibrous tissue, grade 3 represented fibrovascular tissue in the excised area reaching the limbus but not invading the cornea, and grade 4 represented true corneal recurrence, with fibrovascular tissue invading the cornea and passing across the limbus .
Data were coded and entered using the Statistical Package for the Social Sciences (SPSS version 24; SPSS Inc., Chicago, Illinois, USA). Data were summarized using mean and standard deviation for quantitative variables and frequencies (number of cases) and relative frequencies (percentages) for categorical variables. Comparisons between groups were done using the unpaired t-test. For comparing categorical data, χ2 test was performed. The exact test was used instead when the expected frequency was less than 5. Correlations between quantitative variables were done using the Pearson correlation coefficient. P values less than 0.05 were considered statistically significant.
| Results|| |
Of the 100 patients in the glue group, 40 were men and 60 were women, with a mean age of 46.08±8.40 years, compared with 50 men and 50 women in the suture group, with a mean age of 45.40±7.52 years. There was no statistically significant difference between the two groups regarding sex and age (P>0.05, [Table 1]).
In addition, there was no statistically significant difference between the two studied groups regarding the preoperative BCVA and astigmatism, postoperative BCVA and astigmatism and preoperative horizontal pterygium size (P>0.05, [Table 1]).
The mean operative time was 20.28±2.73 min in the glue group and 31.04±6.52 min in the suture group, with a statistically significant difference between the two groups (P=0.000, [Table 1]).
There was an increase in the BCVA and a decrease in astigmatism postoperatively in both groups, with a statistically significant differences between their preoperative and postoperative values (P<0.05, [Table 2]).
|Table 2 Comparison between preoperative and postoperative BCVA and astigmatism in both groups|
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At the first postoperative day, pain, foreign body sensation, and lacrimation were reported by all patients in the suture group, whereas in the glue group, pain was reported in all patients, foreign body sensation was reported in 40 patients (P<0.001), and lacrimation was reported in 70 patients (P<0.001). Pain and foreign body sensation persisted beyond the first week in 44 patients in the suture group and in only five patients in the glue group, with a statistically significant difference between the two groups (P<0.001, [Table 3]).
|Table 3 Comparison between the groups regarding postoperative symptoms, signs, and complications|
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Postoperative subconjunctival hemorrhage was reported in five patients in the glue group and in 15 patients in the suture group, with a statistically significant difference (P=0.033, [Table 3]). None of the patients in either group had developed graft edema or granuloma. Graft displacement and loss occurred in three patients in the glue group and in one patient in the suture group, with no statistically significant difference between the two groups (P=0.7, [Table 3]). The four eyes that had graft loss showed recurrence.
Recurrence occurred in three patients in the glue group (one male and two female) and in 12 patients in the suture group (seven males and five females), all of whom experienced recurrence during the first 6 months postoperatively, with a statistically significant difference between the two groups (P=0.031, [Table 3]).
The donor site healed well within 14 days in all cases, allowing possible future ocular surgery if required.
| Discussion|| |
The current study included 200 patients who were divided into two groups: glue group and suture group. The baseline demographics regarding age distribution, male-to-female ratio, and preoperative grading of pterygium in the two groups were comparable, with no significant difference.
The operative time was significantly shorter in the glue group (20.28±2.73 min) than in the suture group (31.04±6.52 min). Reduction in the operative time has important implications for both patients and surgeons. For surgeons, the use of fibrin glue will shorten the learning curve and make the operation easier.
Gong et al.  performed a study to assess the long-term efficacy and safety of self-made cryopreservative fibrin glue (SMC) applied in pterygium surgery with a conjunctival autograft. It included 40 eyes of 40 patients with nasal primary pterygium, divided into two groups. In one group, the autograft was attached to the sclera with the SMC stored for 2 months before surgery, and in the other group, a commercial fibrin glue kit (CK) was used. Follow-up ranged from 6 to 18 months, and there were no significant differences in age, sex, and pterygium area encroaching into the cornea between the two groups. The mean surgery time was 18.6±2.4 min in the SMC group and 18.9±3.0 min in the CK group, with no statistically significant differences between the two groups (P=0.713).
Anbari  conducted a study on 54 patients (90 eyes) with nasal primary or recurrent pterygium for whom surgical excision with conjunctival autograft obtained from the same eye was done. The patients were divided into two groups. Autologous cryoprecipitate, which was prepared 48 h before surgery by obtaining 45 ml of patient’s blood, was used in 47 eyes (glue group) and absorbable sutures (8/0 vicryl) were used in 43 eyes (suture group) to attach the free conjunctival graft. The follow-up period ranged from 6 to 18 months. The mean surgical time was significantly shorter (11±2 min) in the glue group compared with the suture group (21±7 min, P<0.05).
There were no significant intraoperative complications in the present study as well as in the studies by Gong et al.  and Anbari .
In the present study, on the first postoperative day, foreign body sensation and lacrimation were statistically significantly lower in the glue group, but pain was reported in all cases in both groups. After the first week, pain and foreign body sensation were also significantly lower in the glue group. As this is the patient’s own serum and we did not use any foreign material, there was nothing to induce inflammation, and there was no issue of market deficiency. Similarly, Gong et al.  found no significant differences in postoperative discomfort between the two groups (P>0.05). Anbari  found that the medians of the visual analog scale values, used to analyze and quantify the severity of pain, were statistically significantly lower in the glue group (P<0.05).
In the present study, postoperative subconjunctival hemorrhage was reported in five patients in the glue group and in 15 patients in the suture group, which was a statistically significant difference. Graft displacement and loss occurred in three patients in the glue group and in one patient in the suture group, with no statistically significant difference. No graft edema or granuloma occurred in either group. Gong et al.  observed yellowish graft edema in some eyes in both groups in the first few days postoperatively, but it resolved gradually and spontaneously. Graft displacement occurred in one patient in the SMC group. On the contrary, Anbari  did not report any significant postoperative complications.
In this study, recurrence of the pterygium occurred in three patients in the glue group, owing to postoperative graft displacement and loss, and in 12 patients in the suture group, owing to graft displacement and loss in one patient, immediate postoperative exposure to environmental risk factors without wearing even protective glasses in seven patients who were farmers, whereas no obvious cause of recurrence was reported in four patients, with the difference being statistically significant between the two groups. All recurrences occurred during the first 6 months postoperatively. It is postulated that gluing the conjunctiva inhibits fibroblast migration into the surgical area, which minimizes the risk of recurrence.
In the study conducted by Gong et al. , no recurrence occurred in the SMC group, whereas it occurred in five cases in the CK group. Anbari  found no recurrence in the glue group, whereas recurrence occurred in 11 patients in the suture group during the first 3 months postoperatively, with all recurrences occurring in cases of previously recurrent pterygium. There was a statistically significant difference in the recurrence rate between the two groups in both studies (P<0.05).Other authors tried to compare one technique with other ones in terms of recurrence. Shrivastava et al.  concluded that there was no significant difference between the commercial fibrin glue and autologous serum regarding the recurrence rate. Singh et al.  found no difference in the recurrence rate between the commercial fibrin glue and suture groups. Similarly, Choudhary et al.  found no significant difference in the recurrence rate between the autologous in-situ blood coagulum and sutures. In addition, Sati et al.  found an equal recurrence rate in three different techniques (commercial fibrin glue, sutures, and autologous blood coagulum) for conjunctival autograft fixation.
In this study, with the use of autologous cryoprecipitate, most of the suture and commercial fibrin glue-related complications were eliminated, and their additional cost was avoided. In addition, the subsequent chance of recurrence was lowered. This technique required shorter surgical time and decreased postoperative discomfort compared with the use of sutures in primary pterygium surgery.
| Conclusion|| |
In conclusion, the use of autologous cryoprecipitate to attach the conjunctival autograft in primary pterygium surgery appeared to be effective, reliable, safe, and quick. In addition, it decreased the recurrence rate. There were no infections or severe related complications after long-term follow-up.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]