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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 16
| Issue : 1 | Page : 30-34 |
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Topical cyclosporine A and interferon alpha-2b as adjuvants to surgery to decrease pterygium recurrence
Usha K Raina, Banu Pavitra, Shruti Bhattacharya, Kumar Ravinesh, Ruchi Goel
Department of Ophthalmology, Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi, India
| Date of Submission | 27-Feb-2022 |
| Date of Decision | 13-May-2022 |
| Date of Acceptance | 19-Nov-2022 |
| Date of Web Publication | 21-Feb-2023 |
Correspondence Address:
Shruti Bhattacharya
B21, Ashoka Apartments, Sector 12, Dwarka, New Delhi - 110 075
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ojo.ojo_56_22
 Abstract | | |
BACKGROUND: Pterygium is very common in India and is usually removed by limbal conjunctival autograft transplantation (LCAT), which, despite being the first-line therapy, is still associated with recurrences of up to 18%.
OBJECTIVES: To compare the safety and efficacy of topical cyclosporine A (CsA) and interferon (IFN) alpha-2b in the prevention of postoperative recurrence of pterygium.
METHODS: A total of 40 patients with primary pterygium were randomized into two equal groups, Group C and Group I. Both the groups underwent LCAT, with Group C kept on topical cyclosporine 0.05% (CsA) 4 times daily and Group I on topical IFN alpha 2b 0.2 million IU 4 times daily postoperatively for 3 months. Pre- and posttreatment best-corrected visual acuity (BCVA), recurrence, and complications were assessed at day 1, week 1, 1 month, and 3 months.
RESULTS: The mean preoperative BCVA of 0.51 ± 0.18 and 0.51 ± 0.23 improved to 0.13 ± 0.13 and 0.13 ± 0.13 in Group C and Group I, respectively, after 3 months of treatment (P < 0.0001). Recurrence was seen in 2 cases in Group C and in 1 case in Group I at 3 months. No significant complications occurred in either of the groups.
CONCLUSION: Topical CsA and IFN Alpha-2b are newer efficacious adjuvants with LCAT for prevention of postoperative pterygium recurrence.
Keywords: Cyclosporine, interferon, limbal conjunctival autograft, pterygium
How to cite this article:
Raina UK, Pavitra B, Bhattacharya S, Ravinesh K, Goel R. Topical cyclosporine A and interferon alpha-2b as adjuvants to surgery to decrease pterygium recurrence. Oman J Ophthalmol 2023;16:30-4 |
How to cite this URL:
Raina UK, Pavitra B, Bhattacharya S, Ravinesh K, Goel R. Topical cyclosporine A and interferon alpha-2b as adjuvants to surgery to decrease pterygium recurrence. Oman J Ophthalmol [serial online] 2023 [cited 2023 Mar 31];16:30-4. Available from: https://www.ojoonline.org/text.asp?2023/16/1/30/370057 |
| Introduction | |  |
Pterygium is a common ocular surface disease of the bulbar conjunctiva, characterized by subconjunctival growth of triangular-shaped fibrovascular tissue with extension onto the cornea.[1],[2] The disorder poses various problems including cosmetic blemish, astigmatism, and ocular motility limitation.
Surgery is the currently the first-line treatment for pterygium, but postoperative recurrence remains the most significant complication, with an aggressive growth potential as compared to a primary pterygium.[3] This recurrence is attributed to chronic inflammation and immune reaction associated with increased secretion of cytokines such as interleukin-2 (IL-2), IL-6, IL-8, and vascular endothelial growth factor (VEGF) and, recently, human papilloma virus.[4],[5]
In surgical methods, the traditional bare-sclera technique is associated with high recurrence rates of 33% to 89%.[5] Multiple treatment options including adjuvants and newer surgical techniques were tried in the past to address the issue. Among the adjuvants, mitomycin-C was predominantly used and proven efficacious in the prevention of recurrence, but its use got limited due to sight-threatening complications such as scleral necrosis and corneal opacification.[6],[7]
Limbal conjunctival autograft (LCAT) is currently the gold standard surgical option.[8] Recurrence after LCAT is low, but is still significant, of up to 18%.[9] However, its limitations include technical expertise, graft-related complications, donor site scarring, and need for repeated surgeries to address the recurrence.[10]
Cyclosporine A (CsA) is a T-cell immunosuppressant, which controls the synthesis and secretion of interleukins and inhibits VEGF and fibroblast proliferation.[11] Based on these properties, topical CsA has been effectively used in various ocular conditions such as vernal keratoconjunctivitis, viral keratitis, and inflammatory dry eye.
Interferons (IFNs) are cytokines secreted by human cells in response to stressors such as infection and tumors. Type 1 IFN includes IFN-alpha and IFN-beta, and type 2 IFN includes IFN-gamma.[12],[13] IFN alpha is a recombinant biological agent with antiviral, antiproliferative, immunomodulatory, and antiangiogenic properties. It has been successfully used in several external ocular diseases that encompass ocular surface squamous neoplasia, viral keratitis, and refractory vernal keratoconjunctivitis.
In order to prevent the recurrence of pterygium with a more targeted approach and to enable consistent outcomes irrespective of surgical expertise, this study aimed to compare and analyze the safety and efficacy of newer adjuvants IFN alpha-2b and CsA.
| Methods | | |
This is randomized, prospective, single-center study approved by the institutional ethics committee. Forty eyes of 40 patients diagnosed with primary pterygium, aged 18 years and above, and who had registered at the outpatient department of a tertiary care center in India were included in the study after written informed consent and they were randomized into two equal groups, Group C and Group I, by computer-generated random numbers.
Both the groups underwent LCAT transplantation surgery, with Group C being kept on topical cyclosporine 0.05% (CsA) 4 times daily and Group I on topical IFN alpha 2b 0.2 million IU 4 times daily postoperatively for 3 months. Patients with recurrent pterygium, ocular surface disorders, extraocular surgery in the past 6 months, uncontrolled systemic diseases, and pregnancy were excluded.
Preoperatively, vision, anterior, and posterior segment examination was done. Pterygium was classified before surgery according to the classification system proposed by Tan et al.,[14] who classified pterygium based on tissue translucency using episcleral vessels visibility as the marker as seen in [Table 1]. They rationalized this by hypothesizing that the decrease in translucency was related to the thickness of the fibrovascular tissue which could potentially help in predicting the recurrence rate postoperatively.
Further, the recurrence was diagnosed and classified based on the classification system proposed by Prabhasawat et al.,[15] as shown in [Table 2].
Pre- and posttreatment best-corrected visual acuity (BCVA), recurrence, and complications were assessed at day 1, week 1, 1st month, and 3rd month.
Surgical technique
After written informed consent, all surgeries were performed by the same surgeon over the course of the study. The surgical technique included the excision of the pterygium tissue with the transplantation of the limbal conjunctival autograft to the bare area, under peribulbar anesthesia.
Initially, the size of the pterygium was measured using Castroviejo calipers. The head of the pterygium was then avulsed from its attachment at the cornea and blunt dissection of subconjunctival fibrovascular tissue was performed. The bare area of sclera was measured with calipers [Figure 1] and the donor graft with size 1–2 mm larger than the bare sclera was harvested from superior bulbar conjunctiva and transplanted onto the bare area, preserving the limbal orientation. The graft was secured with 8-0 vicryl sutures.
In the postoperative period, patients were given topical antibiotics and lubricants for a three week period. The pre- and posttreatment BCVA, recurrence, and complications were assessed at day 1, week 1, 1st month, and 3rd month.
Statistical analysis
Data analysis was done using Statistical Package for the Social Sciences (SPSS, IBM, USA) version 25.0.
Quantitative variables such as age were compared using unpaired t-test/Mann–Whitney test (when the data sets are not normally distributed) between the two groups. Qualitative variables were compared using Chi-square test/Fisher's exact test. P < 0.05 was considered statistically significant.
| Results | | |
Forty eyes of 40 patients aged 18 years and above, who had registered at the outpatient department in a tertiary care center in India, diagnosed with primary pterygium were included in the study.
The average age of the study participants was 41.45 ± 10.57 years. Group C patients had a mean age of 39.9 ± 9.57 years and Group I had 43 ± 11.52 years (P > 0.05). 29 of the patients included were male (72.50%), and there were 11 female. The most common additional ocular pathology was pterygium in the fellow eye. There was no statistical difference between the groups in demographic profile and preoperative grades of pterygium.
Postoperatively, there were no graft-related complications such as displacement, retraction, or infection. 75% of the patients had clear cornea at 3rd month, with the rest of patients having a small residual peripheral nebular corneal opacity where the pterygium had encroached upon the cornea.
The mean preoperative BCVA of 0.51 ± 0.18 and 0.52 ± 0.23 improved to 0.13 ± 0.13 and 0.13 ± 0.13 in Group C and Group I, respectively, 3 months after the treatment (P < 0.0001), as shown in [Table 3]. | Table 3: Comparison of best-corrected visual acuity between Group C and Group I
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Recurrence was seen in 2 cases in Group C, and in 1 case in Group I at 3 months, as shown in [Table 4].
| Discussion | | |
Pterygium is a common ocular surface pathology, frequently encountered in the tropics, that is associated with prolonged unprotected ultraviolet light exposure, and viral infections, causing chronic inflammation, and tumor-like proliferation.[1],[2]
Detokaris et al. proposed a “two hit” theory for pterygium progression.[16] The first hit was the genetic damage mediated by the ultraviolet light, whereas the second hit was an oncogenic event mediated by viral infection in susceptible cells.
Risk factors known to cause recurrence include age (increase risk in younger patients), gender, the grade of pterygium, and concurrent ocular surface inflammation.[17] In our study, we analyzed various demographic characteristics and found no significant differences between the groups in age, gender, or grade of pterygium. We found that the majority of patients diagnosed were males working in outdoor environment, probably owing to the increased exposure to ultraviolet light.
A large number of surgical methods including grafts and adjuvant medications have been used in the past to reduce the recurrence of pterygium.
Kenyon et al. saw low recurrence rates following conjunctival autograft.[18] In this technique, it was believed that the proliferation and growth of the pterygium tissue is eliminated by contact inhibition and mechanical barrier effect. However, significant recurrence was reported in subsequent studies. The inclusion of limbal stem cells in the conjunctival autograft restores the anatomic integrity and acts as a barrier to the migration of conjunctival epithelial cells onto the cornea, thus aiding in prevention of recurrence.[19] LCAT is currently the procedure of choice, but even it has recurrence rates of up to 18%.[9]
Adjuvants such as CsA and IFN are used along with LCAT to reduce this recurrence. CsA is a T-cell immunosuppressant that inhibits the synthesis and secretion of inflammatory cytokines. The similarity between pterygium histopathology and action of topical CsA supports its effectiveness in the inhibition of the recurrence.[20] Tok et al. reported a recurrence rate of 12.9% with topical CsA 0.05% applied twice a day for 6 months following simple excision and primary closure.[21] Aydin et al. also reported a low recurrence rate of 3.4% on treatment with topical CsA twice a day for 3 months following limbal conjunctival transplantation.[22] Similarly, in our study, Group C with CsA as an adjuvant had a recurrence in of 2 cases at 3 months with no complications.
IFN is characterized by its antiviral, antiproliferative, antiangiogenic, and immunomodulatory properties. Esquenazi first reported that topical IFN alpha-2b could regress neovascularization significantly in the early stage of recurrent pterygium.[12] Di Girolamo et al. also stated that IFN-alpha serves as an anti-inflammatory and antiproliferative agent by inhibiting mitogen-activated protein kinases pathway in cultivated pterygium epithelial cells to downregulate the secretion of VEGF and inflammatory cytokines.[3] In addition, various in vitro studies have also shown the effect of IFN-alpha in upregulation of Fas-mediated apoptosis of human tenon fibroblast cells IFN was shown to be effective in treating early scarring of the filtering bleb, by inhibiting fibroblast proliferation. It has been found by few studies that IFN also inhibits viral DNA replication, which may also be a reason for it to prevent the recurrence of pterygium. Yin et al. have shown that the recurrence often occurred in the 3–6 months period and reported a recurrence rate of 3.7% at 6 months on treatment with topical IFN alpha 2b 4 times daily for 3 months.[13] In our study, Group I had only one recurrence among 20 eyes, on treatment with IFN alpha-2b 4 times daily for 3 months with no complications noted.
In addition, we noticed a significant improvement in BCVA at 3rd month in both the groups with clear cornea in majority of the patients.
What is novel about our study is that while a few previous studies have compared CsA and IFN alpha-2b against LCAT alone, there has been no comparison of CsA and IFN against each other within the same study.
The limitations of our study were a small sample size and shorter duration of follow-up. Large multicentric trials are needed for more definitive results.
Therefore, while LCAT is the procedure of choice, the sizable amount of recurrences after it can be reduced by the use of adjuvants like cyclosporine or IFN–Alpha 2b without any significant complications. Hence, we conclude that topical CsA and IFN-alpha 2b are efficacious adjuvants to LCAT in prevention of pterygium recurrence.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4]
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