Wound healing in glaucoma filteration surgery

1. WOUND HEALING-
GLAUCOMA FILTERATION SURGERY
MAY 24 2020
Dr Shayri Pillai
Ist Year Ophthalmology Resident
Liberia Eye Centre
JFK Memorial Medical Center
L V Prasad Eye Institute

2. INTRODUCTION
Since de Wecker first described the “filtering cicatrix”, as a
surgical treatment for glaucoma in 1882
Glaucoma filtering surgery (GFS) differs from most surgical
procedures in that inhibition of wound healing is desirable
to achieve surgical success

3. » Successful glaucoma filtering surgery (GFS)
characterized by:
Formation of a filtering bleb, a subconjunctival
accumulation of aqueous humor, which is associated with
a lowered (IOP), generally in the low teens
Healing of the conjunctival incision is essential for bleb
formation
Fistula through which aqueous drains into the
subconjunctival space must remain patent

4. Use of pharmacological modulating agents such as
mitomycin C (MMC) and 5-fluorouracil (5-FU)2–6 has
increased the success of trabeculectomy in patients
with poor prognoses

5. WOUND HEALING MODULATION –
TRABECULECTOMY

6. A trabeculectomy bleb undergoes different phases of
postoperative wound healing:
First Phase
 An immediate Inflammatory response that occurs in
the initial postoperative days
Characterized by:
 Recruitment of inflammatory cells, cytokines and
growth factors, triggering the onset of the second
phase

7. On the first postoperative day
Routine assessments-
Anterior chamber depth
Character, extent,and elevation of the bleb
Conjunctival wound closure and integrity
IOP
Posterior pole

8. Second Phase
 Proliferation and tissue reparation, which
commences in the early postoperative days and can
continue into the second or third postoperative
months
Comprises:
 Activation, migration and proliferation of episcleral
fibro-blasts, angiogenesis and the formation of
collagen bundles

9.  Following filtration surgery, it is ideal to maintain
the IOP between the high single digits to low mid-
teens
(7 to 12) with a low diffuse superonasally placed bleb
 Low diffuse conjunctival elevation with minimal
vasculature,multiple fine microcysts, nonthin-walled
conjunctiva, and indistinct margins are the
hallmarks of a well-functioning and long-lived fil
tration bleb

10. Third and final phase
 Remodelling and final healing of the wound
Comprises:
 Contraction of the collagen fibers and formation of
scar tissue occurs, ultimately resulting in
reduction of aqueous drainage and sub
conjunctival absorption

11.  The ideal course following filtration surgery is to
control
the IOP below the anticipated target pressure
 In phakic patients, the bleb that is identified with
successful control of IOP often is diffuse, slightly
elevated, avascular, succulent, and superiorly
placed with no visible boundaries

12.  Healing under the scleral fap may also play a role in some
cases
 Fibroblasts in Tenon's capsule that are the main effector
cells in the initiation and mediation of trabeculectomy
wound healing and fibrotic scar formation

13. Histopathology of filtering bleb following wound healing
post-trabeculectomy
 Conjunctiva fibrosis/scar formation reduces aqueous
filtering in the surgically treated glaucomatous eye and
shrinks the conjunctival sac during healing
 Loss of conjunctival flexibility due to fibrosis
hinders wound surface resurfacing rendering the
tissue
vulnerable to microbial infection

14.  Variations in the aqueous humor TGF-β2 ratio between
its active and inactive forms are postulated to modulate
the filtering bleb, and fibrotic reactions induced by local
fibroblasts
 Increasing aqueous humor growth factor and cytokine
levels, injury to (sub)conjunctival tissue resulting from
surgical intervention activates local tissue cells
 IL have important roles in immunomodulatory functions
including cell proliferation, maturation, migration and
adhesion regulating immune cell differentiation and
activation

15.  TGF-β upregulates Connective Tissue Growth
Factor
(CTGF) expression, which is one of the most
important
fibrogenic cytokines
 Topical application of the ROCK inhibitor, Y-27632,
improved the outcome of experimental glaucoma
filtration
surgery presumably by suppressing fibrogenic
collagen deposition in tissue around blebs

16.  MMPs are a group of proteolytic enzymes
degrading most extracellular matrix proteins during
ECM remodeling
 Lysyl oxidase (LOX) and lysyl oxidase-like (LOXL)
are
ECM enzymes crosslinking substrates such as
collagen
and elastin, which leads to fibrosis

17.  Vascular endothelial growth factor (VEGF) is a potent
mediator of vascular homeostasis, i.e., angiogenesis,
vasculogenesis and vascular endothelial cell
permeability
 Angiogenesis is an important component of wound
healing leading to fibrosis
 VEGF concentration is elevated after glaucoma surgery
and plays a key role promoting cell proliferation

18.  Angiotensin II has many biological functions
besides including increasing cell proliferation,
apoptosis, migration, inflammatory responses
and ECM remodeling
 Angiotensin-converting enzyme inhibitors
and angiotensin receptor (AT1) antagonists
suppressed
vascular damage by inhibiting tissue fibrosis

19. Among the wound healing promoting-
Cytokines/growth factors, TGF-β is the most
efficacious mediator of conjunctival scarring elicited
by injury
.

20.  Adjunctive application of mitomycin C (MMC)
or 5-fluorouracil (5-FU) after filtering surgery is
performed to attenuate postoperative subconjunctival
fibroblasts proliferation for suppressing excessive bleb
scarring
 These adjunctive anti-metabolites have much improved
the success rate of trabeculectomy

21. 5-fluorouracil
5-fluorouracil (5-FU) inhibits fibroblast proliferation by
retarding
DNA synthesis
less aggressive antimetabolite than mitomycin C
Substantial complications can still occur,
notably persistent corneal epithelial defects and bleb leakage
Intraoperative use involves the application of one or more
small cellulose sponges soaked in a 50 mg/ml solution,
placed
under the dissected flap of Tenon’s capsule at the site of
filtration
for 5 minutes prior to creation of the scleral trapdoor

22. Postoperative subconjunctival injection of 0.1 ml of 25 mg/ml
or 50 mg/ml solution can be used
 Placement may be away from the fistula, even at the
opposite limbus
 Daily injections for several postoperative days and ad hoc
use if a drainage bleb appears to be unduly vascularized
or fibrotic
 It is also often used as an adjunct to a limited ‘needling’
revision of a trabeculectomy

23. Mitomycin C
 Mitomycin C (MMC) is an alkylating agent that inhibits
proliferation of fibroblasts and suppresses vascular
ingrowth
 More potent than 5-FU
 It is generally used intraoperatively
 0.2 mg/ml for 2 minutes, though a higher concentration
(e.g.0.4 mg/ml) may be used for particularly high-risk
patients
 Higher concentrations and extended exposure times
are associated with an increased risk of complications

24.  A cystic thin-walled bleb is common following the use of
mitomycin C
 Predispose to chronic hypotony, late-onset bleb leak and
endophthalmitis
 Bleb profile can be considerably improved by placing the
MMC soaked sponges well away from the limbus

25. Bevacizumab
 Bevacizumab is a monoclonal antibody against
VEGF that can be used at the time of trabeculectomy
 Intracameral or subconjunctival bevacizumab is
more effective than placebo
 It appears to increase the risk of bleb encapsulation
 It is not more effective than mitomycin C and
combining it with MMC does not appear to improve
the success rate

26. Different stages of wound healing after glaucoma filtering surgery.

27. Risk factors for surgical failure:
 Previous failed trabeculectomy or MIGS
 Previous conjunctival or cataract surgery
 Secondary glaucoma (e.g. inflammatory,
neovascular,
post-traumatic)
 Demographic: black ethnicity, age under 65 years
 Patients on topical medication (particularly
sympathomimetics) for over 3 years

29. L V Prasad Eye Institute
www.lvpei.org
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