This document discusses various antifibrotic agents used in ophthalmology, including 5-fluorouracil, mitomycin C, and amniotic membrane. 5-fluorouracil inhibits DNA synthesis to reduce fibroblast proliferation and is used after glaucoma surgery and for ocular surface tumors. Mitomycin C inhibits cell proliferation and is applied during pterygium removal and glaucoma surgery to prevent scarring. Amniotic membrane promotes wound healing and inhibits scarring. It is used for ocular surface reconstruction after injuries or surgery.

1. ANTIFIBROTIC AGENTS IN
OPHTHALMOLOGY
CHAIRPERSON: DR. N.R GUPTA
PRESENTER: DR. NARINDER

2. ANTIFIBROTIC AGENTS
A drug that inhibits or reduces fibrosis .
Types of antifibrotic agents
 5-Fluorouracil
 Mitomycin C
 Amniotic membrane
 Other Antifibrotics Agents

3. 5-FLUROURACIL
 It is pyrimidine analogue antimetabolite, which
blocks DNA synthesis through the inhibition of
thymidylate synthesis , has been shown to inhibit
fibroblast proliferation in cell culture.

4. USES
 5-FU to reduce fibroblastic proliferation and
subsequent scarring has made it an important
adjunct in ocular and periorbital surgeries.
 It is used in primary glaucoma filtering surgeries
and in reviving failing filtering blebs, in
dacryocystorhinostomy, pterygium surgery, and in
vitreoretinal surgery to prevent proliferative
vitreoretinopathy.

5.  5-FU is also gaining recognition in the treatment
and surgical management of ocular surface
malignancies like ocular surface squamous
neoplasia; however, the specific action of the drug
on highly proliferating cells limits its use in primary
acquired melanosis of the conjunctiva.
 It an important tool in enhancing the success rate
in ophthalmic surgery and in reducing the
recurrence of ocular surface neoplasia.
Dose:-5mg for 7-14 days twice-daily subconjuctival
injection.

6. CONTRAINDICATIONS
 It is contraindicated in patients that are severely
debilitated or in patients with bone marrow
suppression due to either radiotherapy or
chemotherapy.
 It is likewise contraindicated in pregnant or
breastfeeding women.

7. ADVERSE EFFECTS
Common (> 1% frequency)
 Local pain
 Itching
 Burning
 Stinging
 Crusting
 Photosenstivity

8. Uncommon (0.1-1% frequency)
 Hyper-or hypopigmentation
 Scarring

9. MITOMYCIN-C
 Mitomycin-C (MMC) is an anti-neoplastic/ antibiotic
agent isolated from soil bacterium Streptomyces
caespitosus.
 MMC was first used in ophthalmology in 1969 in
Japan, where recurrent pterygium were
successfully treated with the drug.
 It is used intravenously to treat upper gastro-
intestinal tumors, anal cancer, breast cancer and
bladder tumors.

10.  In eye surgery, it is applied topically to prevent
recurrence in pterygium surgery, to prevent scarring
during glaucoma filtering surgery and haze after
Photorefractive keratectomy (PRK) or LASIK.
 Its use and application in ophthalmology has been
increasing in recent years because of its
modulatory effects on wound healing.

11. MECHANISM OF ACTION
 It is an anti-metabolite with anti-proliferative effect
on cells showing the highest rate of mitosis by
inhibiting DNA synthesis and interferes with RNA
transcription and protein synthesis.
 The cell cycle is most affected during the late G-I
and early S-phase.

12. CLINICAL USES OF MITOMYCIN C IN
OPHTHALMOLOGY
 Pterygium surgery
 Glaucoma filtering surgery
 Refractive surgeries
 Ocular surface tumors
 Squint surgeries
 Dacryocystorhinostomy (DCR)
 Allergic conjunctivitis.

13. PTERYGIUM SURGERY
 The pterygium is a horizontally oriented, triangular
growth of subconjunctival tissue that invades the
cornea.
 Dose: 0.2-0.4 mg/ml applied intra-operatively over
bare sclera for 1-5 minutes.
 Most impressive results with pterygium were
double masked, prospective trial using doses of
0.4mg/ml (0.04%) and 1mg/ml four times daily for
two weeks; they showed a recurrence rate of 2.2%
compared with the placebo rate of 88.9% after 5
months of follow up .

14.  A detailed report of 10 cases with serious, vision-
threatening complications associated with
Mitomycin-C use after pterygium surgery has been
published when a concentration of 0.4% was used
post-operatively for up to 3 weeks .
 Secondary glaucoma
 Corneal melting
 Corneal perforation
 Scleral calcification

15. OTHER COMPLICATIONS OF MMC IN
PTERYGIUM SURGERY INCLUDE
 Pain
 Excessive tearing
 Photophobia
 Prolonged hyperemia
 Chemosis
 Lid edema
 Wound dehiscence
 Corneal blood staining
 Pigment accumulation
 Superficial punctate keratitis and delayed wound
healing

16. GLAUCOMA FILTERING SURGERY
 The high failure rate of trabeculectomy surgery is
partly due to subconjunctival or scleral scarring at
bleb.
 MMC inhibits the fibroblasts proliferation and
subsequent scarring of filtration bleb.
 Intraoperative MMC applied at concentration of
0.2mg/ml controlled post-operative intra-ocular
pressure (IOP) as effectively as a 0.4mg/ml
concentration in high risk cases of congenital
glaucoma, but with lower incidence of complications
and thin walled blebs .

17.  No significant difference was seen in overall
success or complication between subconjunctival
and intra-scleral application of MMC augmented
trabeculectomies in glaucomatous eyes at high risk
of surgical failure .
 In selected pediatric cases of primary or secondary
glaucoma in which visualization of the trabecular
meshwork is poor trabeculectomy augmented with
MMC and 5-FU is a good treatment option.

18. Dose: 0.2-0.4mg/ml
Complications: Development of thin walled cystic
blebs, late bleb leaks, bleb infections,
endophthalmitis, chronic hypotony, hypotonic
maculopathy and corneal epithelial toxicity.

19. REFRACTIVE SURGERIES
 Haze formation with loss of corneal transparency
and surface irregularities and myopic regression
are the major complications after corneal refractive
surface surgery.
 The use of Mitomycin-C with its antibiotic and anti-
neoplastic properties is intended to inhibit wound
healing mechanisms leading to sub-epithelial
fibrosis.
 Dose:- 0.2mg/ml (0.02%) for 12 to 120 seconds
 Single application of diluted MMC 0.02% solution
following scraping of the corneal surface was
effective and safe in treating haze and regression
after PRK for myopia .

20. OCULAR SURFACE TUMORS
 Ocular surface tumors include a variety of
neoplasms originating from squamous epithelium,
melanocytes, and lymphocytic resident cells of the
conjunctival stroma.
 MMC selectively inhibits DNA synthesis.
 Topical MMC can treat satellite and multifocal
lesions and the entire ocular surface.
 It has been used successfully as adjunctive therapy
for controlling conjunctival and corneal squamous
cell carcinoma even in extensive recurrent disease

21. SQUINT SURGERIES
 Topical Mitomycin-C may enhance the success rate
of strabismus surgery with delayed adjustment and
reduce post-operative adhesions.
 Intra-operative application of MMC is reported in
cases of restrictive squints. It helps to reduce
fibrosis and scarring under the tenons layer.
 Dose: 0.2mg/ml for 5 minutes between the
conjunctiva and the sclera after adhesion release.

22. DACRYOCYSTORTHINOSTOMY
 The most important cause of failure of DCR surgery
is fibrosis occurring under the flaps near the
osteotomy sites.
 MMC in these cases tends to suppress fibrous
proliferation and scar formation intra-operatively.
 MMC application is effective in increasing the
success rate of DCR surgery and no significant
complications resulted from its use.

23.  A piece of cotton soaked with 0.2mg/ml MMC is
applied to the osteotomy site for 30 minutes intra-
operatively is effective in maintaining a larger
osteotomy size and also improves success rates
over the traditional DCR procedure.
 Dose: 0.02 to 0.04% for 5-30 minutes.
 Allergic conjunctivitis :In a study topical MMC
(0.2mg/10ml) was applied four times a day for 3
months and was found to be safe and effective
alternative to topical azelastine, in treating allergic
conjunctivitis.

24. OCULAR COMPLICATIONS OF
TOPICAL MITOMYCIN C
 Minor complications like ocular pain, photophobia,
lacrimation, lid edema, foreign body sensation
(secondary to superficial punctate keratitis).
 Major complications are rare include scleral
ulceration, necrotizing scleritis, perforation, uveitis,
cataract, glaucoma and symblepharon formation.

25. WHEN TO USE 5-FU VS MMC?
 For most primary trabeculectomies, those patients
at minimal risk of failure, we prefer 5-FU. We apply
it intraoperatively with administration of 5-FU
injections postoperatively as needed, depending on
the postoperative course.
 We use MMC for eyes at higher risk of bleb failure.
This includes patients who have undergone
previous ocular surgery, those with uveitic and
neovascular glaucoma, and young patients.

26.  We use 5-FU postoperatively when there is
significant focal inflammation around the bleb that
persists. We administer the drug as a 5 mg dose in
0.1 cc subconjunctivally.
 Unlike mitomycin C, the risk of toxicity is low with
intracameral exposure of low doses of 5-FU. Thus,
the injection can be performed adjacent to the bleb
in many instances.

27. AMNIOTIC MEMBRANE
 Amniotic membrane is the innermost layer of the
placenta consisting of a thick
basement membrane and an avascular stromal
matrix. It can been used as a graft and as a
dressing to facilitate ocular surface reconstruction
and to promote healing.
 Amniotic membrane enhance growth and
differentiation of conjunctival epithelial cells and is
reported to inhibit subconjunctival scar tissue
formation.
 Amniotic membrane is considered to be a favorable
substrate for ocular surface reconstruction.

28. CHARACTERISTICS OF AMNIOTIC
MEMBRANE
 Amniotic membrane is the inner membrane of the
fetal membrane .
 It consists of a thick continuous basement
membrane and an avascular stromal matrix that
contain a high concentration of basic fibroblast
growth factor , basement membrane components
and several trophic factor .
 Recent advances indicates AM has anti-
inflammatory, anti-proteolytic and antimicrobial
activity.

29. INDICATIONS OF AMNIOTIC
MEMBRANE TRANSPLANTATION
 AMT in the presence of stem cell deficiency
-Ocular chemical injury
 AMT in the absence of stem cell deficiency
-Corneal epithelial defects
-Corneal / corneoscleral ulcers
-Bullous keratopathy
 AMT for conjunctival reconstruction
-Pterygium
-OSSN
-Limbal dermoid
-Symblepharon

30. -Conjunctival lesions
-Leaking blebs
 AMT in ocular cicatricial diseases
-Toxic epidermal necrolysis
-Ocular cicatricial pemphigoid
-Oculopalpebral and reconstructive surgery
 Other indications of AM use
-Stem cell cultures

31. OTHER ANTIFIBRIOTIC AGENTS
 Bleomycin
 Rapamycin
 Doxorubicin
 Daunorubicin
 5-fluorouridine
 Heparin
 Taxol
 Colchicine