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Avellino corneal dystrophy test clinical implication
Pietro ROSETTA MD
AVELLINO UNIVERSAL TEST EARLY DIAGNOSIS OF INHERITED CORNEAL DISORDERS
American Academy of Ophthalmology
AvellinoTestsPerformed
534011 (May 16 2016)
2008
2016 3
Pa entsProtected
647
Cornea Dystrophy History and Definition
A group of inherited disorders that are usually bilateral symmetric slowly progressive and not
related to environmental or systemic factors
Groenouw A Knoetchenfoermige
Hornhauttruebungen (Noduli corneae)
Arch Augenheilkd 189021281ndash289
(2008-2015) IC3D International Committee for the Classification of Corneal Dystrophies
IC3D Classification of Corneal DystrophiesmdashEdition 2
Jayne S Weiss MD Hans Ulrik Moslashller MD PhDdagger Anthony J Aldave MDDagger Berthold Seitz MDsect
Cecilie Bredrup MD PhDpara Tero Kivelauml MD FEBOk Francis L Munier MD
Christopher J Rapuano MDdaggerdagger Kanwal K Nischal MD FRCOphthDaggerDagger Eung Kweon Kim MD PhDsectsect
John Sutphin MDparapara Massimo Busin MDkk Antoine Labbeacute MD Kenneth R Kenyon MDdaggerdaggerdagger
Shigeru Kinoshita MD PhDDaggerDaggerDagger and Walter Lisch MDsectsectsect
The IC3D Anatomic Classification
Epithelial and subepithelial dystrophies
Epithelialndashstromal TGFBI dystrophies
Stromal dystrophies
Endothelial dystrophies
classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer
TGFBI Corneal Dystrophy Transforming Growth Factor Beta-Induced protein
1 ReisndashBucklers corneal dystrophy (RBCD) C1
2 Thiel-Behnke corneal dystrophy (TBCD) C1
3 Lattice corneal dystrophy type 1 (LCD1) C1mdashvariants (III IIIA IIIIA IV) of lattice corneal dystrophy C1
4 Granular corneal dystrophy type 1 (GCD1) C1
5 Granular corneal dystrophy type 2 aka
Avellino Corneal Dystrophy (GCD2) C1
TGFBI Gene is located on the long (q) arm of chromosome 5 at position 31
TGFBI Gene Position 31
TGFBI Corneal Dystrophies The mutations are all single point mutations
6
TGFBI Corneal Dystrophies
Mutant TGFBIp
ECM components
Impaired degradation (defective autophagy-
lysosome system)
Accumulation of deposits in the cornea
Han KE et al Pathogenesis and treatments of TGFBI corneal dystrophies Progress in Retinal and Eye Research (2015) E-Pub ahead of print
Transforming growth factor beta-induced protein (TGFBIp) in the cornea
bull Regulates cell-collagen
interactions bull Modifies cellular adhesions bull Maintains components of the
ECM bull Binds to collagen I II IV bull Produced in the epithelium
(keratoepithelin) bull Upregulated during wound
healing in the keratocytes near the wound
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
AVELLINO UNIVERSAL TEST EARLY DIAGNOSIS OF INHERITED CORNEAL DISORDERS
American Academy of Ophthalmology
AvellinoTestsPerformed
534011 (May 16 2016)
2008
2016 3
Pa entsProtected
647
Cornea Dystrophy History and Definition
A group of inherited disorders that are usually bilateral symmetric slowly progressive and not
related to environmental or systemic factors
Groenouw A Knoetchenfoermige
Hornhauttruebungen (Noduli corneae)
Arch Augenheilkd 189021281ndash289
(2008-2015) IC3D International Committee for the Classification of Corneal Dystrophies
IC3D Classification of Corneal DystrophiesmdashEdition 2
Jayne S Weiss MD Hans Ulrik Moslashller MD PhDdagger Anthony J Aldave MDDagger Berthold Seitz MDsect
Cecilie Bredrup MD PhDpara Tero Kivelauml MD FEBOk Francis L Munier MD
Christopher J Rapuano MDdaggerdagger Kanwal K Nischal MD FRCOphthDaggerDagger Eung Kweon Kim MD PhDsectsect
John Sutphin MDparapara Massimo Busin MDkk Antoine Labbeacute MD Kenneth R Kenyon MDdaggerdaggerdagger
Shigeru Kinoshita MD PhDDaggerDaggerDagger and Walter Lisch MDsectsectsect
The IC3D Anatomic Classification
Epithelial and subepithelial dystrophies
Epithelialndashstromal TGFBI dystrophies
Stromal dystrophies
Endothelial dystrophies
classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer
TGFBI Corneal Dystrophy Transforming Growth Factor Beta-Induced protein
1 ReisndashBucklers corneal dystrophy (RBCD) C1
2 Thiel-Behnke corneal dystrophy (TBCD) C1
3 Lattice corneal dystrophy type 1 (LCD1) C1mdashvariants (III IIIA IIIIA IV) of lattice corneal dystrophy C1
4 Granular corneal dystrophy type 1 (GCD1) C1
5 Granular corneal dystrophy type 2 aka
Avellino Corneal Dystrophy (GCD2) C1
TGFBI Gene is located on the long (q) arm of chromosome 5 at position 31
TGFBI Gene Position 31
TGFBI Corneal Dystrophies The mutations are all single point mutations
6
TGFBI Corneal Dystrophies
Mutant TGFBIp
ECM components
Impaired degradation (defective autophagy-
lysosome system)
Accumulation of deposits in the cornea
Han KE et al Pathogenesis and treatments of TGFBI corneal dystrophies Progress in Retinal and Eye Research (2015) E-Pub ahead of print
Transforming growth factor beta-induced protein (TGFBIp) in the cornea
bull Regulates cell-collagen
interactions bull Modifies cellular adhesions bull Maintains components of the
ECM bull Binds to collagen I II IV bull Produced in the epithelium
(keratoepithelin) bull Upregulated during wound
healing in the keratocytes near the wound
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Cornea Dystrophy History and Definition
A group of inherited disorders that are usually bilateral symmetric slowly progressive and not
related to environmental or systemic factors
Groenouw A Knoetchenfoermige
Hornhauttruebungen (Noduli corneae)
Arch Augenheilkd 189021281ndash289
(2008-2015) IC3D International Committee for the Classification of Corneal Dystrophies
IC3D Classification of Corneal DystrophiesmdashEdition 2
Jayne S Weiss MD Hans Ulrik Moslashller MD PhDdagger Anthony J Aldave MDDagger Berthold Seitz MDsect
Cecilie Bredrup MD PhDpara Tero Kivelauml MD FEBOk Francis L Munier MD
Christopher J Rapuano MDdaggerdagger Kanwal K Nischal MD FRCOphthDaggerDagger Eung Kweon Kim MD PhDsectsect
John Sutphin MDparapara Massimo Busin MDkk Antoine Labbeacute MD Kenneth R Kenyon MDdaggerdaggerdagger
Shigeru Kinoshita MD PhDDaggerDaggerDagger and Walter Lisch MDsectsectsect
The IC3D Anatomic Classification
Epithelial and subepithelial dystrophies
Epithelialndashstromal TGFBI dystrophies
Stromal dystrophies
Endothelial dystrophies
classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer
TGFBI Corneal Dystrophy Transforming Growth Factor Beta-Induced protein
1 ReisndashBucklers corneal dystrophy (RBCD) C1
2 Thiel-Behnke corneal dystrophy (TBCD) C1
3 Lattice corneal dystrophy type 1 (LCD1) C1mdashvariants (III IIIA IIIIA IV) of lattice corneal dystrophy C1
4 Granular corneal dystrophy type 1 (GCD1) C1
5 Granular corneal dystrophy type 2 aka
Avellino Corneal Dystrophy (GCD2) C1
TGFBI Gene is located on the long (q) arm of chromosome 5 at position 31
TGFBI Gene Position 31
TGFBI Corneal Dystrophies The mutations are all single point mutations
6
TGFBI Corneal Dystrophies
Mutant TGFBIp
ECM components
Impaired degradation (defective autophagy-
lysosome system)
Accumulation of deposits in the cornea
Han KE et al Pathogenesis and treatments of TGFBI corneal dystrophies Progress in Retinal and Eye Research (2015) E-Pub ahead of print
Transforming growth factor beta-induced protein (TGFBIp) in the cornea
bull Regulates cell-collagen
interactions bull Modifies cellular adhesions bull Maintains components of the
ECM bull Binds to collagen I II IV bull Produced in the epithelium
(keratoepithelin) bull Upregulated during wound
healing in the keratocytes near the wound
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
The IC3D Anatomic Classification
Epithelial and subepithelial dystrophies
Epithelialndashstromal TGFBI dystrophies
Stromal dystrophies
Endothelial dystrophies
classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer
TGFBI Corneal Dystrophy Transforming Growth Factor Beta-Induced protein
1 ReisndashBucklers corneal dystrophy (RBCD) C1
2 Thiel-Behnke corneal dystrophy (TBCD) C1
3 Lattice corneal dystrophy type 1 (LCD1) C1mdashvariants (III IIIA IIIIA IV) of lattice corneal dystrophy C1
4 Granular corneal dystrophy type 1 (GCD1) C1
5 Granular corneal dystrophy type 2 aka
Avellino Corneal Dystrophy (GCD2) C1
TGFBI Gene is located on the long (q) arm of chromosome 5 at position 31
TGFBI Gene Position 31
TGFBI Corneal Dystrophies The mutations are all single point mutations
6
TGFBI Corneal Dystrophies
Mutant TGFBIp
ECM components
Impaired degradation (defective autophagy-
lysosome system)
Accumulation of deposits in the cornea
Han KE et al Pathogenesis and treatments of TGFBI corneal dystrophies Progress in Retinal and Eye Research (2015) E-Pub ahead of print
Transforming growth factor beta-induced protein (TGFBIp) in the cornea
bull Regulates cell-collagen
interactions bull Modifies cellular adhesions bull Maintains components of the
ECM bull Binds to collagen I II IV bull Produced in the epithelium
(keratoepithelin) bull Upregulated during wound
healing in the keratocytes near the wound
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
TGFBI Corneal Dystrophy Transforming Growth Factor Beta-Induced protein
1 ReisndashBucklers corneal dystrophy (RBCD) C1
2 Thiel-Behnke corneal dystrophy (TBCD) C1
3 Lattice corneal dystrophy type 1 (LCD1) C1mdashvariants (III IIIA IIIIA IV) of lattice corneal dystrophy C1
4 Granular corneal dystrophy type 1 (GCD1) C1
5 Granular corneal dystrophy type 2 aka
Avellino Corneal Dystrophy (GCD2) C1
TGFBI Gene is located on the long (q) arm of chromosome 5 at position 31
TGFBI Gene Position 31
TGFBI Corneal Dystrophies The mutations are all single point mutations
6
TGFBI Corneal Dystrophies
Mutant TGFBIp
ECM components
Impaired degradation (defective autophagy-
lysosome system)
Accumulation of deposits in the cornea
Han KE et al Pathogenesis and treatments of TGFBI corneal dystrophies Progress in Retinal and Eye Research (2015) E-Pub ahead of print
Transforming growth factor beta-induced protein (TGFBIp) in the cornea
bull Regulates cell-collagen
interactions bull Modifies cellular adhesions bull Maintains components of the
ECM bull Binds to collagen I II IV bull Produced in the epithelium
(keratoepithelin) bull Upregulated during wound
healing in the keratocytes near the wound
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
TGFBI Gene is located on the long (q) arm of chromosome 5 at position 31
TGFBI Gene Position 31
TGFBI Corneal Dystrophies The mutations are all single point mutations
6
TGFBI Corneal Dystrophies
Mutant TGFBIp
ECM components
Impaired degradation (defective autophagy-
lysosome system)
Accumulation of deposits in the cornea
Han KE et al Pathogenesis and treatments of TGFBI corneal dystrophies Progress in Retinal and Eye Research (2015) E-Pub ahead of print
Transforming growth factor beta-induced protein (TGFBIp) in the cornea
bull Regulates cell-collagen
interactions bull Modifies cellular adhesions bull Maintains components of the
ECM bull Binds to collagen I II IV bull Produced in the epithelium
(keratoepithelin) bull Upregulated during wound
healing in the keratocytes near the wound
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
TGFBI Corneal Dystrophies
Mutant TGFBIp
ECM components
Impaired degradation (defective autophagy-
lysosome system)
Accumulation of deposits in the cornea
Han KE et al Pathogenesis and treatments of TGFBI corneal dystrophies Progress in Retinal and Eye Research (2015) E-Pub ahead of print
Transforming growth factor beta-induced protein (TGFBIp) in the cornea
bull Regulates cell-collagen
interactions bull Modifies cellular adhesions bull Maintains components of the
ECM bull Binds to collagen I II IV bull Produced in the epithelium
(keratoepithelin) bull Upregulated during wound
healing in the keratocytes near the wound
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Transforming growth factor beta-induced protein (TGFBIp) in the cornea
bull Regulates cell-collagen
interactions bull Modifies cellular adhesions bull Maintains components of the
ECM bull Binds to collagen I II IV bull Produced in the epithelium
(keratoepithelin) bull Upregulated during wound
healing in the keratocytes near the wound
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Reis-Bucklers amp Thiel-Behnke Corneal Dystrophies
Weiss JS Moslashller HU et al IC3D classification of corneal dystrophies--edition 2 Cornea 2015 Feb34(2)117-59
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
TGFBI Corneal Dystrophies
GCD1 Hyaline Formations
GCD2 Hyaline and Amyloid
LCD1 Amyloid Formations
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
TGFBI Corneal Dystrophies
Treatment
Penetrating keratoplasty can improve vision at least temporarily but deposits tend to recur
Patients treated with PTK may do better and can retain corneal clarity for a decade or more
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Pre and Post
PTK
Groenouwrsquos Distrophy
Courtesy of Paolo Vinciguerra MD
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Exacerbation after trauma
13
TGFBI Gene Mutation (for
wound healing)
Damage To Cornea (by UV or refractive
procedure)
Excessive Production
Of TGFBI Protein
Protein Deposits on Cornea
LASIK has been reported to exacerbate the number and density of the opacities
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Why Genetic Test
bull Patient Safety Evaluation preventive therapy before clinically detectable damage to tissues has occurred
bull Safety Corneal Surgery LASIK PRK Keratoplasty Cross Linking Premium Cataract
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
In 2002 the first case report of exacerbation of
GCD2 after LASIK was published in Cornea by
EK Kim and colleagues
Exacerbation after LASIK
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Exacerbation after LASIK
25 yo female with undiagnosed GDC2 underwent LASIK in the left eye only Seven years later opacity formations were significantly worsened in the left eye
OD No Surgery OS 7 Years After LASIK
Roo Min Jun MD et al Opthalmology III3 (2004)463-468
Right eye pre-op Right eye 4 years after LASIK Compliments of Anthony Aldave MD
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Autosomal Dominant Inheritance Pattern
Unaffected Affected
bull These 5 corneal dystrophies (CD) are inherited in an autosomal dominant pattern
bull If one parent carries one gene for CD (heterozygous) children have a 50 chance of also having CD
bull If one parent carries two genes for CD (homozygous) children have a 100 chance of also having CD
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Granular Corneal Dystrophy
Homozygote
24 year old
20 year old
Heterozygote after LASIK
Accelerated vision loss
Heterozygote
25 years
28 years
No systemic disease is associated with this disorder
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Granular corneal dystrophy type 2
Epithelial ingrowth
Corneal stromal opacities
ReisndashBucklers dystrophy
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
bull Curr Opin Ophthalmol 1996 Aug7(4)71-82
Corneal dystrophies and keratoconus
Bron AJ1 Rabinowitz YS
bull Br J Ophthalmol 200387367-368 doi101136bjo873367
Letter
Association of keratoconus and Avellino corneal dystrophy S Igarashi1 Y Makita2 T Hikichi3 F Mori3 K Hanada3 A Yoshida3
bull Aust N Z J Ophthalmol 1996 Nov24(4)369-71
Association of keratoconus with granular corneal
dystrophy
Vajpayee RB1 Snibson GR Taylor HR
Does CXL exacerbate the number and density of the opacities
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Premium IOL vs High Order Aberrations
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Diagnosis of Inherited Corneal Disorders Is Genetic Analysis Necessary
Neither a positive family history nor characteristic clinical features are reliable means of differentiating between inherited and non-inherited corneal disorder
Molecular genetic analysis is the most definitive means of distinguishing between the two
Why a DNA test
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Molecular genetic testing provides a rapid inexpensive non-invasive definitive means of
Identifying individuals at risk of significant complications following keratorefractive surgery
Differentiating between dystrophic and neoplastic corneal protein deposition
Differentiating between dystrophic and degenerative corneal opacifications
Diagnosing suspected dominant corneal dystrophies in the absence of family history
Why a DNA test
Thank You for your attention
pietrorosettahumanitasit
Thank You for your attention
pietrorosettahumanitasit
