The Diagnosis and Management of Corneal Dystrophies

Susan J. Gromacki, O.D., M.S., F.A.A.O., F.S.L.S.Diplomate

Cornea, Contact Lenses, and Refractive TechnologiesThe American Academy of Optometry

The Diagnosis and Management of Corneal Dystrophies

Susan J. Gromacki, O.D., M.S., F.A.A.O., F.S.L.S.

Disclosures: AccuLens, Alcon, Alden, Allergan, Bausch + Lomb, Bioscience Communications, Blanchard, CIBA Vision, CooperVision, Danker, Focus Labs, Glaukos,

GPLI, Inspire, Johnson & Johnson, Osmotica/RVL, Pilkington Barnes-Hind, Sauflon, SLES, Sunsoft, SynergEyes, Valeant, Visionary Optics, Vistakon, Wesley-Jessen, and Westcon

Corneal Dystrophy

•Bilateral

•Symmetric

•Centrally located

•Avascular

•Hereditary (autosomal dominant) and usually unrelated to systemic disease

•Early in onset

•Only slowly progressive

Corneal Degeneration

• A deterioration or change in the corneal tissue, making it less functional

• Secondary to aging, trauma, inflammation, or systemic disease

Corneal Degeneration

•Unilateral

•Asymmetric

•Peripheral or eccentric

•Vascularization

•No inheritance pattern or genetic predisposition

•Onset middle life or later

• Lesions are progressive

Corneal Dystrophies

Newest Classification: IC3D (International Committee for Classification of Corneal Dystrophies) edition 2; Cornea 2015

•Epithelial and Subepithelial

•Epithelial-Stromal TGFBI (transforming growth factor beta induced)

•Stromal

•Endothelial

Epithelial and SubepithelialDystrophies

Epithelial Basement Membrane Dystrophy(EBMD)

•Most common anterior dystrophy

•Third + decade of life: maps, dots, and/or fingerprints

• Map-Dot-Fingerprint Dystrophy

• Anterior Basement Membrane Dystrophy (ABMD)

• Cogan’s Microcystic Corneal Dystrophy

Epithelial Basement Membrane Dystrophy(EBMD)

•Visual loss usually minimal

•Treatment: early cases, AT;

•Debridement; debridement + amniotic membrane; Phototherapeutic Keratectomy (PTK)→ but can recur

• Later, tx recurrent corneal erosions (10%)

Treating a Recurrent Corneal Erosion

• Acute: cyclopentolate or homatropine 2%; topical antibiotic qid. Bandage SCL if large

• Topical or oral anti-inflammatories (personal preference)

• After healed: AT 4-8X/day & AT ung qhs X 3mos+ or 5%NaCl gtt 4-8X/day & ung qhs

• If corneal epithelium loose: debridement

• If non-responsive: consider anterior stromal puncture, Phototherapeutic Keratectomy (PTK), or amniotic membrane

Phototherapeutic keratectomy (PTK)

• Excimer laser sequentially ablates uniformly thin layers of anterior corneal tissue

• Similar to PRK but only approved by the FDA for:• Corneal dystrophies

• Irregular corneal surfaces

• Corneal scars and opacities

• May be performed in-office with topical anesthetic drops

• Removes anterior stromal opacities or eliminates elevated corneal lesions

• Creates a smooth stromal surface to improve postoperative corneal clarity, decrease existing scarring and facilitate epithelial adhesion

• Complications: refractive errors (most commonly hyperopia) corneal scarring, and glare

PTK for Corneal Dystrophies

• Less aggressive and faster visual rehabilitation than PKP

• If stromal deposits, laser ablation may result in an irregular surface• Deposits may be ablated at different rate than normal

stroma• Corneal surface not smooth prior to ablation

• AT should be used prior to procedure to help by pooling in the valleys

•May remove superficial opacities and leave deeper ones→ delay corneal transplantation

• If attempt deep stromal ablation, higher chance of permanent haze

Meesman Dystrophy (Juvenile Hereditary Epithelial Dystrophy)

•Clear vesicles interpalpebral -> fine lines t/o cornea

• “Peculiar Substance”

•Visual loss usually minimal

•Tx: recurrent corneal erosions

Epithelial-Stromal TGFBI Dystrophies

Reis-Bucklers Dystrophy

• Bluish-white ring-shaped opacities

• Fishnet or honeycomb appearance

• Painful recurrent corneal erosions (3-4X/year)

• 4th decade: replacement of Bowman layer by scar tissue

Reis-Bucklers Dystrophy

• Tx: RCE; irregular astigmatism: GP CL,

PTK, Penetrating

Keratoplasty

(“PKP” or “PK”)

Corneal TransplantationManagement Strategies:

• Indications: • When all non-surgical options have

been exhausted

• Patient vision still poor

• Selecting a surgeon: • Experience and reputation

Penetrating Keratoplasty (PKP)

•Full-thickness corneal transplant

•Excellent visual outcomes

•Most common complication is astigmatism (30% specs, 47% CL)

•Rejection rate 8-39%• Most often due to the endothelial

layer being replaced

•Do not last forever!Joslin C, Wilson B, Barr JT, et al. Clinical Outcomes in

Keratoconus Following Penetrating Keratoplasty. Optometry

and Vision Science Supplement, December 2003: 221.

Deep Anterior Lamellar Keratoplasty (DALK)

•Partial-thickness cornea transplant that involves selective transplantation of the corneal stroma, leaving the patient’s Descemet membrane and endothelium in place

•Trephinate the host cornea to a depth of 90%

• Inject fluid or air to separate layers

•Remove patient stroma

•Remove donor Descemet and endothelium and trephinate

•Place donor tissue in bed and suture into place

DALK (compared with PKP)

Advantages:

•*Endothelium maintained• Need a healthy, functioning

endothelium prior to the procedure

• Decreased risk of endothelial rejection

•No “open sky”

•Prev. inferior visual outcomes d/t interface, now equal

Disadvantages:

•Technically more demanding and time consuming• If Descemet perforates, convert to PKP

(9-14%)

•Epithelial rejection 2-15%, Stromal rejection 1-2%, Infection 0.8%, similar astigmatism

•More opacification at the interface layers

Macintyre R, Chow SJ, Chan E et al. Long-term outcomes of deep anterior lamellar keratoplasty versus

penetrating keratoplasty in Australian keratoconus patients. Cornea. 2014 Jan; 33(1): 6-9.

Granular Dystrophy Type 1

•White opacities in superficial stroma of central cornea

• 7th-8th decade: opacities enlarge, coalesce and deepen

•Hyaline

•Good VA since stroma b/w lesions remains clear

• Tx: RCE; irregular astigmatism: GP CL, PTK, PKP (recur)

62 yo wf, Judge

•Granular Type 1 Dystrophy

•PKP→ dystrophy recurred

•20/60, 20/70 specs

• Irregular astigmatism

•Oblate corneal shape after transplant

•Poor comfort and retention with corneal GP lens

Solution:

• Scleral GP lenses OU

• Rigid surface provides a new refracting surface and excellent optics

• Lens vaults the cornea, protecting the lesions

• Tear reservoir underneath the lens fills in imperfections of the cornea• Corrects irregular astigmatism• Use a non-preserved artificial tear for this purpose to provide extra

lubrication

• Lens rests on the conjunctiva/sclera to provide excellent centration• Excellent retention

• Excellent comfort

• VA 20/25, 20/30

Lattice Dystrophy

• Refractile lines, anterior-to-mid-stromal dots and faint central haze, subepithelial round opacities

• Stroma b/w remains clear until later in life

• Amyloid

• 6-7 different mutations (“types”)

• Tx: RCE; irregular astigmatism: GP CL, PTK (some), DALK or PKP (recur)

Granular Dystrophy Type 2(formerly Avellino Dystrophy)

• Granular (early onset) and lattice (later) changes in same eye

• Hyaline and amyloid

Stromal Dystrophies

Macular Dystrophy

•Diffuse, grayish-white spots in central portion of anterior stroma→ 3rd

decade: extends to endothelium and limbus→ Descemet membrane opacified and endothelial guttata

•Mucopolysaccaride

Macular Dystrophy

•Autosomal recessive

•Severe vision loss

•Tx: RCE (infrequent), irregular astigmatism: GP CL, PKP• Lamellar not indicated

since leaves damaged endothelium→ recurrence

Schnyder (Crystalline) Corneal Dystrophy

•Round, oval, discoid, or annular central opacity composed of needle-shaped crystals, sometimes with arcus and limbal girdle

•Cholesterol

Schnyder (Crystalline) Corneal Dystrophy

•AD- also assoc. with systemic disorder: hyperlipidemia

•Vision remains good despite appearance

•Tx: rare (PTK, PKP)

Fleck Dystrophy

•Small, discrete, dandruff-like specs in the stroma that extend to the periphery

•VA good

•Tx: none

Endothelial Dystrophies

Congenital Hereditary Endothelial Dystrophy (CHED)

• Least common endo. dystrophy• No longer CHED 1 (too rare) and

CHED 2

• Epithelial and stromal edema t/o cornea

• Defective formation of the endothelium in utero

• AD (1st few years of life) or AR (at birth, nystagmus)

• Tx: hypertonic agents, hair dryer (dehydrates the cornea), PKP (d/t stromal “ground glass opacification”)

Posterior Polymorphous Dystrophy

• 2018: localized the variation to the DNA on gene GRHL2• Genome sequencing using

a large family from the Czech Republic

• 2-20 vesicles surrounded by a diffuse gray halo

• Collagen

• Severe cases: stromal and epithelial edema

Posterior Polymorphous Dystrophy

•VA normal in most patients

•Tx: hypertonic agents, hair dryer

•Surgical intervention dictated by amount of corneal edema

Evolution of Corneal Transplantation for Endothelial Dystrophies

• 10 yrs ago PKP→ DSEK/DSAEK→ DMEK today

• DSEK=Descemet stripping endothelial keratoplasty

• DSAEK=Descemet stripping automated endothelial keratoplasty• “A”= automated

• Uses microkeratome to cut the tissue

DMEK=Descemet membrane endothelial keratoplasty •Vs. PKP: decreased likelihood of graft rejection, less

induced astig, and avoids potential suture removal

•Vs. DSAEK: eliminates the stromal carrier used→results in lower higher order aberrations and faster visual recovery

•Thinner, so more difficult to perform, resulting in complications if not performed correctly (graft loss during preparation, rebubbling, and endothelial cell loss)

DMEK Tissue

•Several eye banks throughout the US process the tissue, facilitating the procedure

•Available to any US surgeon

• “Pre-loaded” or “patient ready” tissue:• Eye bank strips the donor tissue, stains it, cuts it to size

and even loads it into the injector• Ships to surgeon in nutrient solution

•Surgeon does not have to prepare the tissue in the operating room• Takes the risk out of the surgeon damaging the tissue

Contact Lens Spectrum, Volume: 29, Issue: August 2014, page(s): 36-38, 40, 42

Normal Cornea

Full thickness PKP

DALK

DSAEK

DMEK

Fuchs Dystrophy

•Most common corneal dx in the US, 4% over age 40

•Rare prior to age 50

•Symptoms: glare and blurred vision, worse upon awakening

•Risk factors:• European descent• Female (3X male)• Smoking• Diabetes• Exposure to UV light

Fuchs Dystrophy

• Pigment dusting and guttata

• Can lead to focal excrescences of Descemet m.-> stromal and epithelial edema-> large epithelial bullae (rupture: severe pain)

• Collagen (thin layer DM, early onset cases)

Fuchs Dystrophy

•Very slowly progressing

•RTC q 3 (if edema causing increased IOP) to 12 mos.

•Tx: hypertonic agents, hair dryer, antiglaucoma gtt, BCL, PKP→DSEK/DSAEK→DMEK

Graft Rejection Classification*

Definite:

• Mild:• 1 to 5 keratic precipitates (KPs: collections of inflammatory cells on the

endothelium)

• Increase in cells within the aqueous

• Less than a 10% increase in total corneal thickness ultrasonically compared with previous visit

*Corneal Preservation Time Study (CPTS)

Graft Rejection Classification*

Definite:

•Severe:• >5 KPs • Cells in the stroma• >10% increase in total corneal thickness ultrasonically

compared with previous visit• Clinically apparent decrease in stromal clarity• Endothelial rejection line• OR increased corneal thickness >10% from previous visit

AND increased aqueous cells

*Corneal Preservation Time Study (CPTS)

Graft Rejection Classification*

Possible/Probable:

• In a previously clear graft, clinically apparent stromal edema affecting stromal clarity with inflammation (KP, aqueous cells, ciliary injection) without an endothelial rejection line

•OR possible presence of a new KP with difficulty distinguishing between KP and pigment

*Corneal Preservation Time Study (CPTS)

New Development for Corneal Dystrophy Diagnosis:AvaGen (Avellino Labs)

• 1st commercially available genetic diagnostic test of its kind for keratoconus and corneal dystrophies

• Next generation sequencing (NGS) technology: examines over 1,000 variants across 75 genes for keratoconus and over 70 mutations of the TGFBI gene for corneal dystrophies

• In-office cheek swab

• Initial launch Oct. 2019; nationwide launch mid-2021

Traditional Methods of Detecting Corneal Abnormalities:

• Slit lamp microscopy: 1910

• Genetic sequencing: 2020 and beyond

USING GENETIC TESTING TO IDENTIFY PATIENTS AT RISK

Avagen Testing Protocol:

EXTRACTION SEQUENCING

REFERENCING &

VARIANT RISK

SCORES

PATIENT

REPORT