Pterygium is a fibrovascular growth of
conjunctiva over cornea at 3 and 9 o’ clocks. It occurs most commonly in hot,
dry and dusty atmosphere, which makes ocular surface dry, inviting the
conjunctival blood vessels to reach the cornea. As cornea is avascular
structure, it cannot maintain its integrity without sufficient tears for the outdoor
workers in hot and dry atmosphere. The degenerative changes in pterygium
formation is accompanied by cellular
proliferation and vascularization of corneal surface. Secretion of pro-inflammatory
substances such as interleukin-1 and tumor necrosis factor-α secondary to long
time ultraviolet (UV) radiation, is a main known factor in the formation of
pterygium1,2. The vascular endothelial growth factor (VEGF), also
increases in pterygium epithelium which is stimulated by TNF-α through UVB
radiation3,4. Ultraviolet induced inflammation and release of
cytokines stimulates proliferation of Tenon’s capsule fibroblasts to produce
fibrovascular tissue of pterygium5.
If
pterygium is left untreated it involves visual axis and leads to loss of
vision. Many procedures are done to treat this problem for example, simple
excision, use of conjunctival autograph and amniotic membrane. As a medical
treatment, interferon, MMC, and anti VEGF are also used but they are expensive
and may have complications and they do not have additional benefit of treating
the dry eyes. So, we conducted study on cyclosporine-A which is already being
used to treat dry eyes and safe even for long term use6.
Cyclosporine is an immune modulating
substance. It is derived from the fungus to lypocladium
inflatum and approved by world health organization as a safe medicine. It decreases the production of
inflammatory cytokines by T-lymphocytes. It has also been used topically to
reduce sub-epithelial infiltrates in epidemic keratoconjunctivitis6.
Systemic use can increase the risk of lymphoma.
Cyclosporine-A shows a selective effect against T-helper cells and
prevents the synthesis and secretion of ILs. Cs-A also blocks angiogenic effect
induced by VEGF. Therefore, we have evaluated the effects on pterygium
recurrences. The aim of this study was to investigate the outcome of topical Cs-A
in prevention of pterygium recurrence after simple excision.
MATERIAL AND METHODS
A comparative study on 130 eyes of 65
patients having bilateral pterygium, encroaching on the cornea at least 2 mm,
was done using convenient sampling. The study was conducted in the department of
Ophthalmology, Liaquat University of Medical and Health Sciences, Jamshoro from
2015 to 2017. The patients with pseudo-pterygium and
other causes of corneal vascularization were excluded from study. After
informed consent and explanation of research procedure, patients were seen on
slit lamp, the extent of pterygium was assessed. Half of the eyes with pterygium
were selected for post-operative cyclosporine and were named as cyclo-eyes and half
fellow eyes were selected for simple excision done by the same surgeon after an
interval of one to two week and were named as non-cyclo eyes. Immediate post-operative
treatment was tobramycin dexamethasone eye ointment twice and moxifloxacin eye
drops three times daily until corneal epithelium was restored, followed by moxifloxacin
and Cyclosporine 0.05% eye drops twice daily until complete healing of ocular
surface. Then moxifloxacin was stopped and only cyclosporine 0.05% eye drops once
daily in the evening were continued upto three months. In the fellow eye only tobramycin dexamethasone
eye ointment and moxifloxacin eye drops were used for complete healing time followed
by tears three times daily up to three months. Follow up was done after one
week, one month, three months and six months. one mm growth of conjunctival
blood vessels on the cornea was considered as recurrence. The results of cyclo-eyes
were compiled and compared with the fellow eyes and processed on SPSS to see
the significance.
The
results were evaluated by SPSS 2014. The variables used were healing time and
pterygium recurrence period in days. Quantitative data were evaluated by
independent samples T-test, paired T-test, and Chi-square test.
RESULTS
Fifty-three
out of 65 patients who completed 6 months follow up were included in the final results.
In cyclo-eyes recurrent pterygium was observed in 04 (07.55%) patients and recurrence
in fellow non-cyclo eyes occurred in 23 (43.40%) patients (Table 1).
Table 1: Bio data of patients having bilateral
pterygium (n=53 each group).
|
Total No: of eyes |
106 |
(100.0%) |
|
Male |
31 |
(58.49%) |
|
Female |
22 |
(41.51%) |
|
Average age |
|
51.00 years |
|
Cyclo-eyes |
53 |
(50.00%) |
|
Non cyclo-eyes |
53 |
(50.00%) |
|
Extent of pterygium |
2 mm to 4 mm |
|
Table 2: Comparisons of results after 6 months follow
up (n=53 each group).
|
Groups |
Cyclo-eyes |
Non-Cyclo-eyes |
|
No: of eyes |
53 (50.00%) |
53 (50.00%) |
|
Recurrence |
04 (07.55%) |
23 (43.40%) |
|
Mean healing time |
21.1354 days |
15.0213 days |
|
Standard deviation |
1.3412 |
1.0413 |
|
P-value |
0.002 |
0.004 |
|
Complications |
None |
None |
Immediate
post-operative use of cyclosporine interferes with healing process. It takes
longer time for healing of corneo-scleral wound produced by pterygium excision.
Mean healing time in cyclo-eyes was 21.1354 ± 1.3412 days and in non-cyclo-eyes was 15.0213 ± 1.0413 days. P-value was 0.002 and 0.004 respectively (table 2).
MM_files/image002.jpg)
Fig. 1: Pterygium
shown pre and postoperatively.
MM_files/image004.jpg)
Fig. 2: Post op picture with Cyclosporin eye drops after 2
weeks and with no cyclosporine drops after 2 weeks.
DISCUSSION
Pterygium is a growth disorder rather than
degenerative condition, and mainly proliferative factors are investigated to
find out etiology and pathogenesis. As sutures can increase the risk of
recurrence therefore bare sclera suture-less technique was used in our patients.
A definitive treatment without recurrence and minimal complications, has yet to
be found. The main culprits for pterygium are UV radiation, dry and hot
atmosphere, which, leads to release of inflammatory vascular growth factors and
formation of pterygium. It varies in people living in the same environment.
Hypersensitivity is also a powerful factor in the pathogenesis of pterygium7.
T-lymphocytes are elevated in the pterygium
tissue. All available data shows the importance of T-lymphocyte-mediated strong
cellular immunity in pterygium pathogenesis. Cs-A selectively suppresses
functions of T-helper lymphocytes and production of both inflammatory cytokines
and inflammatory mediators.
It also suppresses IgE production in a
T-cell-dependent manner and inhibit histamine release from basophil and mast
cells8.
In vivo and in vitro studies have showed
that Cs-A inhibits angiogenesis triggered by VEGF. We believed that inhibiting
all those paths with Cs-A, which are thought to have a role in pterygium
pathogenesis, might be effective in preventing recurrence9. Cs-A
0.05% is effective in inhibiting the fibroblasts proliferation in Tenon’s
capsule10.
In another similar study, thiotepa and
cyclosporine were compared following pterygium excision where Cs-A was found to
be significantly more effective than thiotepa11.
In Turan-Vural study recurrence rate was 44.4%
in simple bare sclera technique but 22.2% with 0.05% post-operative cyclosporine
and no side effect except mild burning sensation. They also used fellow eye as
control in patients having bilateral pterygium and reported recurrence in 12.9%
with cyclosporine and 45.2% in simple bare sclera technique12,13.
In literature, recurrence of pterygium
after simple excision exceeds 50%. In our study, we have used tears for three
months which might have reduced the recurrence rate even in simple excision. Topical
Cs-A plays a role in the inhibition of T lymphocyte proliferation and suppression
of the inflammation of the ocular surface. It is reported in literature that
topical Cs-A is effective in various concentrations in ocular inflammation
cases such as vernal keratoconjunctivitis, ulcerative keratitis in rheumatoid
arthritis, anterior uveitis, corneal graft rejection, superior limbic
keratoconjunctivitis, graft versus host disease, mycotic keratitis, Cogan
syndrome, Behçet’s disease, herpetic stromal keratitis, Mooren ulcer, atopic
keratoconjunctivitis and scleritis14. Topical 0.05% Cs-A relieves dryness of eyes in meibomian gland
dysfunction without significant systemic or ocular side effects when compared to Bevacizumab
and mitomycin-C15.
Treatment
of patients with dry eye disease for 12 months with topical 0.05% Cs-A does not
cause changes in the corneal endothelium.16 According to Duke-Elder,
pterygium occurs frequently on the nasal side of conjunctiva. This can be explained
on the basis of light, which is coming to the temporal cornea and focused on
the nasal side. Pterygia on the temporal side are rare and should be
differentiated from squamous cell tumor. Double-headed pterygium, is very rare,
only 2.5%17.
In a retrospective
study, it was seen that Pterygium recurrence rate was 5.3% with glue, versus
13.5% with sutures in conjunctival autograft18. Recurrence of 3.3%
was reported with stem cell graft by another researcher19. Our
recurrence rate was 06% in the Cyclosporine group, which was more than the
recurrence observed by Aydin et al18. (3.4%), but lower than
observed by Tok et al. (12.9%)17. It may be higher than observed by
Aydin et al because of the study population of only vascularized and recurrent
pterygium, which is more prone for higher recurrence compared to primary
pterygium20.
CONCLUSION
This short-term
study has given promising results in reducing pterygium recurrence after
primary excision. As pterygium is common in tear deficient eyes. It worsens
with advancing age. Cyclosporine is effective in reducing the ocular surface
dryness and pterygium recurrence. Neat and clean pterygium excision and
post-operative topical use of cyclosporine is very safe and effective method to
prevent recurrence of pterygium. Long term use of cyclosporine 0.05% eye drops
twice daily is harmless to the ocular surface and intraocular structures. This is
cheaper and safer method and should be adopted to reduce the risk of pterygium
recurrence. Therefore, use of cyclosporine after primary excision is
recommended.
ACKNOWLEDGEMENT
I am
thankful to my professor Sameen Afzal Junejo who always encouraged us for
research projects.
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