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Our Eyes – the Gateway to the World
Stage-Related Therapy of
Congenital Aniridia
Berthold Seitz, Barbara Käsmann-Kellner, Arne Viestenz
Seitz B, Käsmann-Kellner B, Viestenz A:
[Stage-related therapy of congenital aniridia.]
Ophthalmologe 2014; 111:1164-1171
Saarland University Medical Center UKS
Saarland University Medical Center UKS
Department of Ophthalmology, Homburg/Saar
Department of Ophthalmology, Homburg/Saar
Chairman: Prof. Dr. med. Berthold Seitz ML, FEBO
Chairman: Prof. Dr. med. Berthold Seitz ML, FEBO
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Basics in Aniridia
Defective Ocular Tissues in Aniridia
Cornea
Iris
Lens
Chamber Angle (Glaucoma)
Incidence: 1:64.000 – 1:96.000
Decreased acitivity of PAX6 gene
on chromosome 11p13
Fovea
Papilla
2/3 autosomal dominant inherited
>> Low Vision 0.1 - 0.3
>> Nystagmus
Wilms tumor predisposition (sporadic)
Stage-Related Therapy of Congenital Aniridia
Reversible Blindness vs. Irreversible Blindness
(Cornea, Lens, Vitreous)
Stage-Related Therapy of Congenital Aniridia
Congenital Aniridia is an „Orphan Disease“
(Optic Nerve, Retina, Brain)
There are still no straight-forward
generally accepted treatment
modalities !!
In the last two decades the
preferred treatment options have
changed dramatically.
Cataract
Corneal Opacities
Glaucoma
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Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Typical Patient‘s Records
Major Treatment Problems
Progressive Anterior
Segment Fibrosis
Syndrome
Tsai JH, Freeman JM, Chan CC et al: A progressive anterior segment fibrosis
syndrome in patients with postsurgical congenital aniridia. Am J Ophthalmol
2005; 140:1075-1079
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Progressive Anterior Segment Fibrosis Syndrome
Progressive Anterior Segment Fibrosis Syndrome
Prevalence ~ 6 - 10%
after intraocular surgery in congenital aniridia
increasing probability with
number of intraocular surgeries
amount of foreign body implantations („hardware“)
non-acute inflammatory fibrotic membrane in AC, originating from iris
stumps
in case of progression dislocation of IOL and corneal decompensation
in case of involvement of ciliary body ocular hypotony and even
tractive retinal detachment
Tsai JH, Freeman JM, Chan CC et al: A progressive anterior
segment fibrosis syndrome in patients with postsurgical
congenital aniridia. Am J Ophthalmol 2005; 140:1075-1079
Initiation and progression may appear without clinical signs of
inflammation in AC
Suspected pathogenesis: Irritation of immature blood vessels in iris
stumps due to surgical intervention or due to iatrogenic foreign
bodies (e.g. large black iris diaphragm IOL )
Histopathology: dense hypocellular fibrouse connective tissue, no
corneal or lens cells
May also develop after glaucoma drainage devices and Boston
keratoprosthesis!
Tsai JH, Freeman JM, Chan CC et al: A progressive anterior
segment fibrosis syndrome in patients with postsurgical
congenital aniridia. Am J Ophthalmol 2005; 140:1075-1079
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Major Treatment Problems
Artificial Iris ?????
Iris Hypoplasia
Brunner SC, Walton DS, Chen TC: Aniridia.
Int Ophthalmol Clinics 2008; 48 (2): 79-85
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Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Options for Compensation of Iris Hypoplasia
Artificial Iris from Gore-Tex
Iris imitating contact lens
Simulation for implantation of (partial) iris prosthesis
Artificial iris into the capsular bag during cataract surgery
We do NOT advocate implantation of artificial irides into
the sulcus –
often worsening of glaucoma !!
risk of „progressive anterior fibrosis syndrome“
Tsai JH, Freeman JM, Chan CC et al: A progressive anterior fibrosis syndrome in
patients with postsurgical congenital aniridia. Am J Ophthalmol 2005; 140:10751079
Gesundes Auge
mit intakter Iris
(Foto als Vorlage)
Verletztes Auge partielle Aniridie
Fixierung der
Iris-Teilprothese
Endergebnis des
operierten Auges
(Die Naht ist praktisch nicht sichtbar)
Dr. Schmidt Intraocularlinsen
GmbH
CAVE: PANAMA - „NewColorIris“
George MK, Tsai JC, Loewen NA: Bilateral irreversible severe vision
loss from cosmetic iris implants. Am J Ophthalmol 2011; 151:872-875
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Instead of Artificial Iris ……
Major Treatment Problems
Glaucomas ~ 50%
Late childhood
Brunner SC, Walton DS, Chen TC: Aniridia.
Int Ophthalmol Clinics 2008; 48 (2): 79-85
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Glaucomas in Children
Pathophysiology of Aniridic Glaucomas
congenital
with congenital
anomalies
Congenital Aniridia
Axenfeld-Rieger Syndrom
Sturge-Weber Syndrom
Marfan-Syndrom
Buphthalmus
Obscuration of trabecular meshwork and limbal spur
by tissue strands containing blood vessels
Rudimentary iris plane prallel to the axis of the eye
(Partial) absence of Schlemm‘s canal
Ninios K, Jonescu-Cuypers CP, Seitz B : Glaukome bei primären
Irisveränderungen - Axenfeld-Rieger-Syndrom, ICE-Syndrome
(essenzielle Irisatrophie, Chandler-Syndrom, Cogan-Reese-Syndrom),
Aniridie. Ophthalmologe 2011; 108:585-593
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Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Chamber Angle
Glaucoma Diagnostics
3 Approaches
Morphology of
Optic Nerve
Head
IOP
Stage-Related Therapy of Congenital Aniridia
Visual Fields
Stage-Related Therapy of Congenital Aniridia
IOP Measurement
Applanation tonometry
Goldmann
Impression tonometry
Schiötz
Icare tonometer
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
IOP Measurement
Photographic Documentation of Optic Nerve Head
Always measure corneal thickness !
Mean:
631 ± 51 µm 1
691 ± 75 µm 2
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Brandt JD, Casuso LA, Budenz DL: Markedly increased central corneal thickness: an
unrecognized finding in congenital aniridia. Am J Ophthalmol 2004; 137:348-350
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Whitson JT, Liang C, Godfrey DG, Petroll VM, Cavanagh HD, Patel D, Fellman RL,
Starita RJ: Central corneal thickness in patients with congenital aniridia. Eye Contact
Lens 2005; 31:221-224
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Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Aniridic Glaucoma
Options of Glaucoma Surgery
Goniotomy
Trabeculotomy
(Visualize Schlemm canal with UBM !)
[ Trabeculectomy with Mitomycin C ]
Glaucoma drainage devices (Molteno, Baerveldt, Ahmed)
Cyclodestructive procedures (CPK) – not CCK!!!
Trabectome - in pseudophakia or simultaneous with phaco ???
NO argon laser trabeculoplasty !
Often the optic disc is difficult to assess ….
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Glaucoma Drainage Devices
Major Treatment Problems
… preferred in the USA …
Lens Abnormalities
and Cataract - 50% - 85%
Lee H, Khan R, O‘Keefe M: Aniridia: current pathology and
management. Acta Ophthalmol 2008; 86:708-715
Corneal decompensation in up to 30% of eyes
Topouzis et al.
Am J Ophthalmol 1999
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
The Lens in Aniridia
The Lens in Aniridia
Fragile anterior lens capsule
Zonular weakness
Morphological changes at the equator
When to operate?
• Direct ophthalmoscopy
• Retinoscopy
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Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Options of Lens Surgery
Morcher Aniridia Ring Type 50C
Foldable blue-light-filtering IOL via 2.0 - 2.5 mm
retrolimbal incision
Morcher aniridia ring type 50C:
designed for intracapsular insertion. Two of these rings
are implanted and turned against each other in order
to produce a full iris diaphragm
Black iris diaphragm IOL (Morcher 67F and 67G)
(sulcus fixated or sutured transsclerally)
(via 10 mm incision with partial destruction of the limbus, does not
fit in the capsular bag) - today no more recommended!!!
… serves as capsular tension ring
in case of zonular weakness …
Riemann C: Place all the „hardware“ in the bag !!
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Morcher Aniridia Ring Type 50C + „Yellow IOL“
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Black Iris Diaphragm IOL
Black Iris Diaphragm IOL
Sundmacher R, Reinhard T, Althaus C: Black-diaphragm intraocular
lens for correction of aniridia. Ophthalmic Surg 1994: 25:180-185
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Stage-Related Therapy of Congenital Aniridia
Black Iris Diaphragm IOL
Stage-Related Therapy of Congenital Aniridia
Iris Diaphragm IOL - Potential Complications
Hyphaema
http://www.sciencedirect.com/science/article/pii/S0181551209000722#fig4
Postoperative uveitis
Chronic corneal endothelial cell loss
Clinically significant macular edema
Progression of corneal epithelial disorder
Seconday glaucoma
Progressive anterior segment fibrosis sydrome
Reinhard T, Engelhardt S, Sundmacher R: Black diaphragm
aniridia intraocular lens for congenital aniridia: Long-term followup. J Cataract Refract Surg 2000; 26:375-381
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Major Treatment Problems
Coloured Iris Diaphragm IOL
http://www.sciencedirect.com/science/article/pii/S0181551209000722#fig4
„Corneal Opacities“
Anirida-Associated Keratopathy (AAK)
20% – 30%
Lee H, Khan R, O‘Keefe M: Aniridia: current pathology and
management. Acta Ophthalmol 2008; 86:708-715
Riemann C: … „barbaric“ … in congenital aniridia
Stage-Related Therapy of Congenital Aniridia
Anirida-Associated Keratopathy (AAK)
OD
OS
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Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Anirida-Associated Keratopathy (AAK)
Anirida-Associated Keratopathy (AAK)
Often starting in the first decade of life
Limbal stem cell deficiency
Conjunctivalization of the cornea
Recurrent corneal erosions and ulcerations
Often worse
after surgery that involves
excessive manipulation of the limbus – or
after application of topical antimetabolites to treat
aniridia-associated glaucoma
Edén U, Riise R, Tornqvist K: Corneal invcolvement in congenital
anirida. Cornea 2010; 29:1096-1102
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Anirida-Associated Keratopathy (AAK)
Anirida-Associated Keratopathy (AAK)
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Non-surgical Treatment of AAK
Surgical Treatment of AAK
Dark glasses against photophobia
Preservative-free and phosphate-free lubricants
Hyaluronic acid containing artificial tears (early prophylactic)
Dexpanthenol ointment at night (early prophylactic)
Autologous serum eye drops
In case of vascularization and inflammation: low dose unpreserved
and phosphate-free steroid
Avoid VEGF-antagonist eye drops !!
Sleral contact lenses (P. Rama)
Jastaneiah S & Al-Rajhi AA: Association of aniridia and dry eyes.
Ophthalmology 2005; 112:1535—1540
Amniotic membrane transplantation AMT (esp. as patch)
(also to improve the limbal stem cell niche ?)
Seitz B, Resch M, Schlötzer-Schrehardt U, Hofmann-Rummelt C, et al.:
Histopathology and ultrastructure of human corneas after amniotic membrane
transplantation. Arch Ophthalmol 2006; 124:1487-1490
Pannectomy „in the correct layer …“, excimer laser PTK,
therapeutic contact lens and 100% autologous serum
Das S, Langenbucher A, Pogorelov P, Link B, Seitz B : Long-term outcome of
excimer laser phototherapeutic keratectomy (o-PTK) for treatment of Salzmann's
nodular degeneration. J Cataract Refract Surg 2005; 31:1386-1391
Lopez-Garcia JS, Rivas L, Garcia-Lozano I, Murube J: Autologous
serum eyedrops in the treatment of aniridic keratopathy.
Ophthalmology 2008; 115:262-267
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… after pannectomy and
excimerlaser PTK
first day postop
Aniridia-assoziierte Keratopathie (AAK)
with central Salzmann‘s nodular degeneration
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Surgical Treatment of AAK
Surgical Treatment of AAK
Limbal stem cell transplantation
Triplet matching of living related donor
Unmatched from organ culture
Keratolimbal allograft
Ex vivo expansion of stem cells on
amniotic membrane or fibrin gel
Holland EJ, Djalilian AR, Schwartz GS: Management of
aniridic keratopathy with keratolimbal allograft: a limbal
stem cell transplantation technique. Ophthalmology 2003;
110:125-130
Systemic immune suppression indispensable !!
Central homologous limbokeratoplasty
14 mm deep lamellar corneoscleral graft, to co-transplant
donor stem cells
14 mm peripherally lamellar, centrally penetrating
corneoscleral graft
(save the scleral spur!)
Sundmacher R & Reinhard T: Central corneolimbal
transplantation under systemic cyclosporine A cover for
severe limbal stem cell insufficiency. Graefs Arch Clin Exp
Ophthalmol 1996; 234:S122-S125
Systemic immune suppression indispensable !!
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Surgical Treatment of AAK
Surgical Treatment of AAK
Central 14 mm Corneoscleroplasty
Central 14 mm Corneoscleroplasty
Spender
Indispensable: Save the scleral spur !!
Systemic immune suppression indispensable !!
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Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Surgical Treatment of AAK
Excimer Laser Keratoplasty with Single Sutures
Penetrating excimer laser keratoplasty
OD
OS
in case of accompanying endothelial decompensation
with simultaneous amniotic membrane patch,
temporary lateral tarsorrhaphy,
100% autologous serum eye drops,
17 mm therapeutic contact lens.
Markus Klingenstein
16121985
Aufn v 050122012
Seitz B, Langenbucher A, Kus MM, Küchle M, Naumann GOH:
Nonmechanical corneal trephination with the excimer laser improves
outcome after penetrating keratoplasty. Ophthalmology 1999; 106:1156-1165
Seitz B, Das S, Sauer R, Hofmann-Rummelt C, Beckmann MW,
Kruse F: Simultaneous amniotic membrane patch in high-risk
keratoplasty. Cornea 2011; 30:269-272
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Excimer Laser Keratoplasty with Single Sutures
Irreversible Graft Failure After Keratoplasty
Problem: Recurrent epithelial defects on the graft !!!
RULE: No corneal transplantation in case of
uncontrolled intraocular pressure preop !!!!
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Surgical Treatment of AAK
Boston Keratoprosthesis Type 1 in Children ??
Boston Keratoprothesis Type 1
Very often exarcerbation of glaucoma afterwards !!
Typically before or afterwards glaucoma drainage device necessary ?
Problem: Retroprosthetic membrane !
Rixen JJ et al: Treatment of aniridia with Boston Type I keratoprosthesis.
Cornea 2013; Feb 26 [Epub ahead of print]
Kang JJ et al: Visual outcomes of Boston keratoprosthesis implantation as
primary penetrating corneal procedure. Cornea 2012; 31:1436-1440
Bakhtiari P et al: Surgical and visual outcomes of the type I Boston
keratoprosthesis for the management of aniridic fiibrosis sndrome in
congenital anirida. Am J Ophthalmol 2012; 152:967-971
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Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Boston Keratoprosthesis in Children ??
Summary I
Congenital anirida is a profibrotic disorder.
Therefore, many interventions - incl. penetrating keratoplasty and
filtering surgery - tend to fail.
Small incision cataract surgery seems to have advantages over large
incisions for black iris diaphragm IOLs („barbaric“).
First option for aniridic glaucoma seems to be trabeculotomy second drainage devices/tubes.
No artifical iris in the sulcus - if any at all, then in the bag during
cataract surgery.
Käsmann-Kellner B & Seitz B:
[Congenital aniridia or PAX6-syndrome?]
Ophthalmologe 2014; 111:1114
Stage-Related Therapy of Congenital Aniridia
Stage-Related Therapy of Congenital Aniridia
Summary II
Conclusions
AAK is treated with unpreserved and phosphate-free
hyaluronic acid containing lubricants, autologous serum,
pannectomy/PTK or amniotic membrane transplantation
(patch).
Only in case of recurrent/persistent epithelial defects and/or
visual deterioration various types of limbal transplantation c/o
lamellar/penetrating keratoplasty is considered.
The Boston KPro may provide a more effective approach in
the management of AAK - in experienced hands …
Despite our increasing understanding of the genetics
and pathophysiology of congenital aniridia,
effective treatment remains elusive
with many of the conditions recurring after surgical
intervention.
Strongly individualized approach (“personalized
medicine”) – stay conservative or at least minimal
invasive!
Seitz B, Käsmann-Kellner B, Viestenz A:
[Stage-related therapy of congenital aniridia.]
Ophthalmologe 2014; 111:1164-1171
Stage-Related Therapy of Congenital Aniridia
Take-Home Messages
General rule:
Stay conservative – if surgery is necessary be
minimal-invasive.
Ophthalmologist are Organ Donors!
There is no „aniridia surgeon“, however the „best glaucoma
surgeon“ should take care of the glaucoma, the „best cornea
surgeon“ should take care of the cornea, and the „best cataract
surgeon“ should take care of the cataract …
A pediatric ophthalmologist and Low Vision specialist
should function as „guide in a network“, to consider the
entire patient and help to achieve the optimal stagerelated therapy for congenital aniridia.
Käsmann-Kellner B & Seitz B:
[Aniridia syndrome. Clinical findings, problematic courses
and suggestions for optimization of care („aniridia
guide“).] Ophthalmologe 2014; 111:1145-1156
Thank you very much for your attention!
[email protected]
www.unilasik-homburg.de
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