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OPHTHALMOLOGY
Volume 52, Issue 21
November 7, 2014
GLAUCOMA SURGERIES AND THE CORNEA
From Glaucoma Surgeries and the Cornea, presented by the New England Ophthalmological Society
Neovascular Glaucoma
Peter A. Netland, MD, PhD, Vernah Scott Moyston Professor and Chair, Department of Ophthalmology, University
of Virginia School of Medicine, Charlottesville
Case 1: 74-yr-old woman had decreased vision after cataract surgery; patient had 20/50 vision in right eye (OD) and could count
fingers at 3 ft with left eye (OS); intraocular pressures (IOPs)
19 mm Hg OD and 18 mm Hg OS; angle almost completely
closed OS; reasonable IOP with nearly closed angle uncommon
presentation in patient with rubeosis iridis; patient had 100%
reduction of flow in left carotid artery, ischemic retinopathy,
and neovascularization of iris and angle; glaucoma of OD also
suspected; treatment with bevacizumab (Avastin) and panretinal photocoagulation (PRP) planned for OS; patient not candidate for carotid surgery; medical therapy instituted because of
increase in pressure to 31 mm Hg OS; vision improved slightly
and IOPs stable in midteens
Case 2: 77-yr-old woman with history of blind, painful OD presented with conjunctival lesion, steamy cornea, and rubeosis iridis; patient had 20/100 vision OS and no light perception OD;
diagnosed with conjunctival melanoma and treated with enucleation; also treated for diabetic retinopathy, central retinal vein
occlusion (CRVO), and clinically significant macular edema OS;
OS now stable; these cases illustrate that therapy for neovascular
glaucoma (NVG) often directed at underlying etiology
Neovascular glaucoma: secondary form of glaucoma; treatment depends on etiology, stage of disease, and visual potential
of patient; NVG has several causes, but universal underlying
mechanism nonperfusion of retinal tissue and (often) release
of vasoproliferative factors; causes include diabetic retinopathy, CRVO, central retinal artery occlusion, tumors, radiotherapy, and chronic retinal detachment
Treatment of NVG: most therapies directed at retinal ischemia;
intravitreal and intracameral inhibitors of vascular endothelial
growth factor have transient effect; following medical treatment with PRP or endolaser, photocoagulation achieves more
sustained effect; treatment of retinal ischemia often beneficial,
and also reduces associated inflammation
Stages of NVG: progressive condition; initially, vascularization of
iris or angle may be observed in presence of normal IOP; in stage
2 disease, IOP may be increased but angle still open; in end stage
(stage 3), angle completely closed and IOP markedly elevated
Medical therapy: in addition to bevacizumab, inflammation
may be treated with prednisolone (eg, Econopred, Omnipred,
Pred Forte); cycloplegia helpful for patient comfort; topical
medications for glaucoma used in patients with elevated IOP;
other useful agents include aqueous suppressants such as
β-blockers, carbonic anhydrase inhibitors, and α2-adrenergic
antagonists; emerging literature also supports use of hyperosmotic drugs such as glycerin, even in patients with diabetes;
prostaglandins and cholinergic medications not used (onset of
action of prostaglandins too slow)
Surgical treatment: trabeculectomy — success rate 66% to 91%
when antifibrosis drugs (eg, mitomycin C [MMC]) used; success
rates low when MMC not used; success rates decrease over time;
addition of bevacizumab to trabeculectomy and MMC improves
success rate; in patient with NVG and elevated IOP who does not
respond to medical therapy, surgeon may consider trabeculectomy
if inflammation under control; although success rate similar to that
of drainage implant in retrospective study, NVG in patients treated
with trabeculectomy less severe and involved little inflammation;
drainage implants — preferred over trabeculectomy in most cases,
including in patients with poor prognoses; success rates modest
(43%-79%), but treatment failures include patients with loss of
light perception; drainage implants successfully control IOP, and
mean IOP in patients with NVG similar to that in patients with
other types of glaucoma; loss of vision despite control of IOP
caused by progression of underlying disease
Bevacizumab: improves visual outcomes and decreases need
for surgical treatment of glaucoma; often allows surgery to be
avoided in patients with stage 2 disease, but not in patients with
closed angle; reduces inflammation and can therefore prepare
eyes for surgery
Guidelines for treatment: stage 1 — underlying etiology treated
in these patients with normal IOP; treatments include bevacizumab and PRP; if needed, pars plana vitrectomy, endolaser
procedure, or removal of cataract performed; stage 2 — underlying etiology treated and medical therapy for glaucoma
administered; patients often respond; stage 3 — although medical therapy sometimes given, most patients require surgery and
should usually receive drainage implant; growth of vessels near
tip of tube commonly observed due to local pattern of flow
Vision: visual potential of patient influences management decisions; expensive treatments may not be worthwhile in patient
who cannot regain vision; for such patients, less aggressive
approaches include retinal cryotherapy, use of transcleral retinal diode probe for retinal photocoagulation, and cyclophotocoagulation; for patient without vision, retrobulbar injection of
alcohol, evisceration, or enucleation may prevent pain
Drainage implants: complications uncommon and manageable; limited cyclophotocoagulation — eg, 180° instead of 270°;
Educational Objectives
Faculty Disclosure
The goals of this program are to improve diagnosis and treatment of glaucoma. After hearing and assimilating this program,
the clinician will be better able to:
1. Explain the pathophysiology of neovascular glaucoma
(NVG).
2. Provide appropriate treatment of NVG.
3. Compare outcomes of trabeculectomy with those of the
mini glaucoma shunt (EX-PRESS) device.
4. Outline the surgical steps involved in performing
Descemet membrane endothelial keratoplasty.
5. Weigh the risks and benefits of transplanting the
Bowman layer for advanced keratoconus.
In adherence to ACCME Standards for Commercial Support,
Audio Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within
the past 12 months that might create any personal conflicts of
interest. Any identified conflicts were resolved to ensure that
this educational activity promotes quality in health care and not
a proprietary business or commercial interest. For this program,
the following has been disclosed: Dr. Melles is a consultant for
D.O.R.C. (Dutch Ophthalmic Research Center [International]).
Dr. Netland reported nothing relevant to disclose. The planning
committee reported nothing to disclose.
AUDIO DIGEST OPHTHALMOLOGY 52:21
effective initial adjunctive treatment; may be repeated if necessary;
more effective than bleb revision or additional drainage implants
Conclusions: treat underlying cause of NVG; late-stage patients
with closed angle often require surgery, usually with drainage
implant; surgeon must individualize therapy according to etiology, stage of disease, and visual potential; clinical judgment
required when visual potential difficult to assess
Trabeculectomy vs Mini Glaucoma Shunt
Dr. Netland
Case: 75-yr-old on maximal medical therapy for glaucoma had
progressive visual field defects and IOP 14 mm Hg; progression of disease confirms diagnosis of normal-tension glaucoma; long-term control of IOP important for this patient
Target for IOP: Collaborative Normal-Tension Glaucoma
Study demonstrated that reducing IOP by 30% slows progression of visual field deficits; based on this study, 30% reduction
of IOP targeted in patients with progression; in this case, IOP
of 10 mm Hg represents 30% reduction
Treatment options: options in this patient include laser trabeculoplasty or selective laser trabeculoplasty (SLT), but incisional
surgical therapy likely to provide more definitive treatment;
use of MMC to achieve lower IOP standard when performing
trabeculectomy; several new procedures also available; most
procedures result in postoperative IOP in mid to high teens, and
therefore not good options for this patient; however, placement
of mini glaucoma shunt filtration device (EX-PRESS) under
scleral flap with MMC, or trabeculectomy with MMC, would
sufficiently lower IOP in this patient
Mini glaucoma shunt: technique similar to trabeculectomy;
however, device reduces tissue trauma because no sclerectomy
or iridectomy performed; associated with fewer complications;
procedure efficient; disadvantages include cost and potential
device-related complications; use of mini glaucoma shunt and
trabeculectomy associated with similar rates of success and
similar postoperative IOPs, but rate of postoperative hypotony
lower in patients treated with mini shunt
Tubal occlusion: in series of 345 patients, complications associated with mini glaucoma shunt included blocked tube in
1% to 2% of patients; inflammatory debris tends to occlude
tube in patients with chronic inflammation; constriction point
just inside tube where diameter decreases to 50 μ, but may be
opened easily with Nd-YAG laser using 2 mJ power
Randomized study: time to visual recovery shorter in group that
received mini glaucoma shunt device than in patients treated
with trabeculectomy; patients treated with device may develop
hypotony, but have significantly lower variance (square of
standard deviation) in IOP; fewer postoperative complications
seen with device than with trabeculectomy
Conclusion: for patient presented, after discussing all options
(including SLT), surgeon recommended incisional surgery with
mini glaucoma shunt under partial-thickness scleral flap, with
use of MMC, for long-term control of IOP
Update on Endothelial Keratoplasty
Gerrit R.J. Melles, MD, PhD, Director, Netherlands Institute for Innovative Ocular Surgery, Columbus, Rotterdam,
Netherlands
Descemet membrane endothelial keratoplasty (DMEK):
involves stripping only Descemet membrane and placing donor
Descemet membrane in anterior chamber; implant not placed
on posterior stroma; hemi-DMEK refers to grafting of half of
membrane to stroma
Technique: preferably, surgeon should use grafts prepared in eye
bank by experienced personnel; may load graft into injector and
place into eye using 3 side ports and main incision; descemetorhexis done in air due to superior refractive index of air compared with water; leaving membrane behind may affect visual
outcome; performing descemetorhexis in air also avoids overhydration of cornea; negative pressure in cornea required for graft
to adhere to posterior stroma; rinsing graft thoroughly removes
organ culture medium; viscoelastic culture medium left in interface may interfere with attachment; graft stained with trypan
blue in glass vial and oriented into double-roll formation; tissue injected into eye with folds pointing upward; endothelium
should be on outside, not on inside as for Descemet stripping
endothelial keratoplasty (DSEK); surgeon should look under fold
to check orientation of graft; to unfold graft, begin over iris; by
tapping on cornea and inflating air between folds, graft becomes
easier to unfold; next, air removed from interface and graft lifted
upward toward posterior stroma; leaving air in anterior chamber
for 1 to 2 hr allows graft to adhere to host cornea; visual outcomes good in eyes with Fuchs endothelial dystrophy (FED); by
6 mo, 80% of patients achieve visual acuity of 20/25; endothelial
cell counts comparable to those observed with Descemet stripping automated endothelial keratoplasty (DSAEK); cell counts
decrease by 30% within first year and continue to decrease thereafter; as in DSAEK, major complication postoperative detachment of graft; surgeon must learn when to rebubble implant, redo
DMEK, or do DSAEK or other indicated procedure
Allograft rejection: after penetrating keratoplasty (PK), DMEK, or
other procedure, patient may present with decreased visual acuity or rejection may be evident on examination; rejection treated
with corticosteroids; detection — in some patients followed with
spectral microscopy imaging before and after surgery, presence
of white and black spots and large nuclei consistent with cellular activation observed; these findings associated with rejection
of graft, and observable before rejection clinically evident; early
detection may permit intensified therapy with corticosteroids to
prevent rejection; spontaneous clearance — eyes with FED may
show spontaneous corneal clearance; some patients with large
detachments report improving visual acuity; however, clearing
does not occur in patients with bullous keratopathy, which suggests that host endothelial cells involved in process of clearance
and repopulation of posterior stroma
Hemi-DMEK: rim of Descemet membrane has rich population
of endothelial cells; although procedure results in lower endothelial cell counts, early results promising
Comparison with PK: DMEK and DSEK associated with better
outcomes and fewer complications
Isolated Bowman Layer Transplantation
for Advanced Keratoconus
Dr. Melles
Case: 20-yr-old with advanced keratoconus, treated with deep
anterior lamellar keratoplasty (ALK), developed infiltration
around sutures, with melting of posterior portion of graft
Treatment of keratoconus: for mild keratoconus, surgeon may
consider ultraviolet-induced cross-linking; for severe cases,
PK or ALK may be considered; Bowman layer transplantation
another option; ALK associated with postoperative complications, and visual acuity outcomes sometimes poor in patients
with keratoconus
Rationale for procedure: although keratoconus considered noninflammatory condition, conjunctiva reacts to sutures and other interventions; association of keratoconus with atopy may explain this
finding; as observed in patients undergoing endothelial keratoplasty,
fewer complications occur when anterior corneal surface left intact; in
patients who undergo ALK, allograft rejection less likely when endothelium left intact; ideal procedure might be performed within stroma,
thereby avoiding anterior and posterior surfaces
Bowman layer: on pathologic specimens, fragmentation of
Bowman layer pathognomonic feature of keratoconus; placing
new Bowman layer to reshape cornea might achieve desired
result; however, Bowman layer only 10-μ thick and not amenable to suturing; approaches with glues have been unsuccessful;
by making stromal bucket and placing Bowman layer inside,
AUDIO DIGEST OPHTHALMOLOGY 52:21
tensile strength provided by Bowman layer may be retained,
but at different corneal level; Bowman layer prepared in eye
bank by peeling layer away from anterior donor cornea, starting at periphery and working toward center; Bowman layer
approximately same thickness as Descemet membrane, so
placing Bowman layer in organ culture results in rolling up of
layer; confusing these layers must be avoided
Technique: during ALK, air injected into anterior chamber to
help guide specula into stroma and find proper depth for corneal
pocket; using same technique, enter cornea at depth of ≈70%; as
for Descemet graft, insert Bowman layer into pocket and unfold
it; Bowman layer strong and may be stretched; if posterior
stroma overhydrated during surgery, posterior portion of cornea
becomes flattened; after inserting Bowman layer in pocket, place
small air pocket above it to displace posterior layers toward iris;
when cornea flattened this way, Bowman layer becomes fixed
Outcomes: transplantation of Bowman layer currently used
only in patients with keratometry (K) measurements of steepness >70 D; procedure achieves flattening of simulated K and
steepest K; minimal damage observed in endothelial cells, and
decrease in cell count does not appear to be progressive; major
complication intraoperative perforation due to splitting of cornea; goal of surgery not to improve visual acuity, but rather
to allow patient to continue to wear contact lenses; procedure
avoids most problems associated with ALK; patient may still
undergo PK or ALK if procedure unsuccessful
Acknowledgements
Dr. Netland and Dr. Melles were recorded at Glaucoma Surgeries and the Cornea, presented by the New England Ophthalmological
Society, and held on May 30, 2014, in Boston, MA. For details on upcoming continuing medical education programs from New England Ophthalmological Society, please visit neos-eyes.org. The Audio Digest Foundation thanks the speakers and the New England
Ophthalmological Society for their cooperation in the production of this program.
Suggested Reading
Anderson DR et al: Factors that predict the benefit of lowering
intraocular pressure in normal tension glaucoma. Am J Ophthalmol
2003 Nov;136(5):820-9; Arcieri ES et al: Efficacy and safety of
intravitreal bevacizumab in eyes with neovascular glaucoma undergoing ahmed glaucoma valve implantation: 2-year follow-up. Acta
Ophthalmol 2014 Jul 2 [Epub ahead of print]; Balachandran C et
al: Spontaneous corneal clearance despite graft detachment in descemet membrane endothelial keratoplasty. Am J Ophthalmol 2009
Aug;148(2):227-234.e1; Baydoun L et al: Endothelial cell density
after descemet membrane endothelial keratoplasty: 1 to 5-year follow-up. Am J Ophthalmol 2012 Oct;154(4):762-3; Dahan E et al:
Comparison of trabeculectomy and Ex-PRESS implantation in fellow eyes of the same patient: a prospective, randomised study. Eye
(Lond) 2012 May;26(5):703-10; Dapena I et al: Learning curve
in Descemet’s membrane endothelial keratoplasty: first series of
135 consecutive cases. Ophthalmology 2011 Nov;118(11):214754; Dapena I et al: Standardized “no-touch” technique for descemet membrane endothelial keratoplasty. Arch Ophthalmol 2011
Jan;129(1):88-94; Güell JL et al: Historical review and update of
surgical treatment for corneal endothelial diseases. Ophthalmol
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Ther 2014 Feb 18 [Epub ahead of print]; Kanner EM et al: ExPRESS miniature glaucoma device implanted under a scleral flap
alone or combined with phacoemulsification cataract surgery. J
Glaucoma 2009 Aug;18(6):488-91; Lupinacci AP et al: Clinical outcomes of patients with anterior segment neovascularization treated with or without intraocular bevacizumab. Adv Ther
2009 Feb;26(2):208-16; Netland PA et al: Randomized, prospective, comparative trial of EX-PRESS glaucoma filtration device
versus trabeculectomy (XVT study). Am J Ophthalmol 2014
Feb;157(2):433-440.e3; Obata H and Tsuru T: Corneal wound
healing from the perspective of keratoplasty specimens with special reference to the function of the Bowman layer and Descemet
membrane. Cornea 2007 Oct;26(9 Suppl 1):S82-9; Shen CC et
al: Trabeculectomy versus Ahmed glaucoma valve implantation in
neovascular glaucoma. Clin Ophthalmol 2011;5:281-6; van Dijk
K et al: Midstromal isolated Bowman layer graft for reduction
of advanced keratoconus: a technique to postpone penetrating or
deep anterior lamellar keratoplasty. JAMA Ophthalmol 2014 Apr
1;132(4):495-501; Wang W et al: Ex-PRESS implantation versus
trabeculectomy in uncontrolled glaucoma: a meta-analysis. PLoS
One 2013 May 31;8(5):e63591.
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Estimated time to complete the educational process:
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Listen to audio program
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Take posttest
5 minutes
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AUDIO DIGEST OPHTHALMOLOGY 52:21
GLAUCOMA SURGERIES AND THE CORNEA
To test online, go to www.audiodigest.org and sign in to online services.
To submit a test form by mail or fax, complete Pretest section before listening and Posttest section after listening.
1. The universal etiology of neovascular glaucoma (NVG) is:
(A) Inflammation
(B) Vascular occlusion
(C) Retinal nonperfusion**
(D) Retinal disease
2. A patient with increased intraocular pressure (IOP) and an open angle is considered to have ________ glaucoma.
(A) Nonprogressive
(B) Stage 1
(C) Stage 2**
(D) Stage 3
3. Which of the following classes of drugs is not used for medical treatment of NVG?
(A) Prostaglandins**
(B) Carbonic anhydrase inhibitors
(C) Corticosteroids
(D) β-blockers
4. In a clinical trial comparing drainage implantation with trabeculectomy, success rates after drainage implantation were
modest because:
(A)
(B)
(C)
(D)
Drainage implantation is inferior to trabeculectomy
Patients in the study did not receive mitomycin C
Patients in the study did not receive bevacizumab
Patients with loss of light perception due to progression of disease were considered treatment failures**
5. Which of the following is the most reasonable treatment in a patient with pain due to glaucoma who has no vision or visual
potential in the eye?
(A) Transcleral retinal photocoagulation
(B) Retrobulbar injection of alcohol**
(C) Retinal cryotherapy
(D) Cyclophotocoagulation
6. Which of the following is the usual primary treatment for a patient with stage 3 NVG?
(A) Bevacizumab
(B) Carbonic anhydrase inhibitors
(C) Trabeculectomy
(D) Drainage implant**
7. The Collaborative Normal-Tension Glaucoma Study demonstrated that progression of visual field deficits can be reduced
by achieving:
(A) IOP of 10 mm Hg
(B) IOP in midteens
(C) 30% reduction in IOP**
(D) Stable IOP
8. Compared with patients treated with trabeculectomy, those treated with the mini glaucoma shunt (EX-PRESS) device had:
(A) Lower postoperative IOP
(B) Fewer postoperative complications**
(C) Longer time to visual recovery
(D) No hypotony
9. Which of the following are recommended techniques for performing Descemet membrane endothelial keratoplasty?
1.
2.
3.
4.
5.
Unfold graft over iris first
Stain graft with Trypan blue
Perform descemetorhexis in organ culture medium
Insert graft with endothelium on inside
Leave air in the anterior chamber
(A) 1,2,5**
(B) 2,3
(C) 3,4,5
(D) 1,2,3,4
10. Which of the following is the major complication of transplantation of the Bowman layer for advanced keratoconus?
(A) Allograft rejection
(B) Intraoperative perforation**
(C) Inability to wear contact lenses
(D) Damage to endothelial cells
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