5/20/2014

Epithelial (Anterior) Basement Membrane CORNEAL DEGENERATION Dystrophy (EBMD or ABMD)

• Non-familial, late onset • Easy to overlook: The Latest In Corneal • Asymmetric, unilateral, central or peripheral – typically bilateral though often asymmetric, Degenerations and Dystrophies • Changes to the tissue caused by inflammation, – females>males, age, or systemic disease. – often first diagnosed b/w ages of 40-70 Blair B Lonsberry, MS, OD, MEd., FAAO Characterized by a deposition of material, a Diplomate, American Board of Optometry • Clinic Director and Professor thinning of tissue, or vascularization Pacific University College of Optometry Portland, OR [email protected]

Epithelial (Anterior) Basement Membrane Epithelial (Anterior) Basement Membrane Dystrophy (EBMD or ABMD) Dystrophy (EBMD or ABMD) • Most common • Primary features of this “dystrophy” are: findings are: – abnormal corneal epithelial regeneration and – chalky patches, maturation, – intraepithelial – abnormal basement membrane microcysts, and • Often considered the most common dystrophy, – fine lines (or any but may actually be an age-related degeneration. combination) in the central 2/3rd of CORNEAL DYSTROPHIES – large number of patients with this condition, – increasing prevalence with increasing age, and – its late onset support a degeneration vs. dystrophy.

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Epithelial (Anterior) Basement Membrane Epithelial (Anterior) Basement Membrane Corneal Dystrophies Dystrophy (EBMD or ABMD) Dystrophy (EBMD or ABMD)

• Group of corneal diseases that are: • Not all patients are symptomatic (range 10- • Often referred to as: – maps, – genetically determined and 69%) • Most common symptom is mild FB sensation – dots or – have been traditionally classified with respect to – fingerprints the corneal layer affected which is worse in dry weather, wind and air conditioning • Emerging molecular science: • Blurred vision from irregular or is redefining traditional thought on the – rapid TBUT dystrophies and • Pain is usually secondary to a RCE (recurrent – offering potential avenues for therapeutic intervention. corneal erosion) in apprx 10%

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Recurrent Corneal Erosion: EBMD-Negative Staining Treatment Amniotic Membrane Transplant • If severe enough to cause vision loss or • Amniotic membrane is a biologic tissue with: repeated episodes: – antiangiogenic, – antiscarring, • oral doxycycline with/without topical corticosteroid – antimicrobial, and – Doxy 50 mg bid and FML tid for 4-8 weeks – anti-inflammatory properties that promotes healing of the ocular – both meds inhibit key metalloproteinases important in surface disease pathogenesis • Amniotic membrane grafts have been used for a variety of ocular – Azasite (topical azithromycin) conditions including: – Corneal burns • debridement, – Neurotrophic ulcers • stromal puncture, or – Stem cell damage • PTK – Persistent epithelial defects • Latest development: amniotic membrane transplant e.g. Prokera

Epithelial (Anterior) Basement Membrane Dystrophy (EBMD or ABMD): Treatment Stromal Puncture Amniotic Membrane Transplant

• Typically directed towards • Traditionally, amniotic membrane grafts had to be preventing RCE sutured • If RCE ’s develop: – With the advent of tissue adhesives, amniotic transplants – awake with painful eye can now be sutureless that improves as day • ProKera was approved by the FDA in 2003 as a Class II wears on medical device which has a polycarbonate ring which – chalky patches/dots in holds a cryopreserved amniotic membrane lower 2/3rd of cornea • ProKera is indicated in the treatment of corneal erosions, neurotrophic , recalcitrant corneal inflammation, acute ocular surface burns, acute Stevens Johnson syndrome, and descemetoceles.

RCE: Treatment CORNEAL DEBRIDEMENT RCE and LASIK

• Soften epithelium • Initial treatment • 1-2 gtt topical anesthetic • Patients who have a history of EBMD may not includes: • q 15-30 seconds for 2-3 be ideal candidates for LASIK and should be minutes – use of hyperosmotic • Use cotton swab, spatula, spud carefully screened for prior to surgery. ointment at • or jewelers forceps • Remove flaps by pulling edges bedtime, toward center – bandage contact • Don ’t pull directly up or out and • Remove flaps down to tight, • firm edges. – lubrication. • Tx abrasion (>50-100%) – Recurrence Rate 18%

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Granular Dystrophy: Macular (Groenouw Type II) Lattice (Type I) (Groenouw Type I) • Grayish opacities in • RCE are common with • The central cornea is the superficial stroma associated pain. progressively opacified resulting is scarring and • With age: • Decreased vision results deterioration of vision – extension into deeper from subepithelial while the periphery stromal layers scarring or dense stromal remains clear. – intervening stroma deposits. • RCE ’s often present. becomes hazy • Surgical treatment • May require surgical – progressive loss of includes penetrating intervention with vision, keratoplasty or DALK diminished vision. – and (Deep Anterior Lamellar – PK ocular discomfort. Keratoplasty). – DALK

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Central Crystalline Dystrophy of Macular Corneal Dystrophy PTK Treatment for GRANULAR Schnyder • Surgical treatment • Opacities consist of: usually required by – small, needle-shaped 2nd or 3rd decade of refractile crystals life. that are either white or polychromatic – PK – may extend into – DALK not indicated deeper stroma but as may have damage epithelium remains to Descemets normal.

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Granular Dystrophy: Central Crystalline Dystrophy of Lattice (Type I) (Groenouw Type I) Schnyder • Discrete white • Characteristic clinical granular opacities in central anterior appearance includes: • Vision is typically mildly affected though there corneal stroma. – linear, maybe associated systemic complications • With age: – refractile, – systemic cholesterol should be evaluated – increasing number, density, size and depth – branching deposits of opacities within the anterior – intervening stroma stroma. and peripheral cornea remain clear

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Penetrating Keratoplasty Deep Anterior Lamellar Keratoplasty (DALK)

• Advantages over PK: – No “open sky” during surgery so lesser chance of expulsive hemorrhage – Much decreased rejection potential because patient keeps their own endothelium • Stromal rejection is rare and easily treated – Low to no rejection risk so steroids are tapered more quickly (usually twice as fast) – Heals faster as steroids tapered sooner allowing sutures to be SURGICAL TREATMENTS: PK AND removed earlier and more rapid visual stabilization (apprx 6 DALK months) – More tectonic stability as patient keeps own endo

PK Surgery: Full Thickness Surgery Deep Anterior Lamellar Keratoplasty (DALK) Normal Changes to the Endothelium

• Removal of all tissue EXCEPT Descemet ’s and • Descemet ’s layer thickens from 3-17u Donor tissue Recipient tissue sutured into endothelium • There is a decrease in the # of endothelial removed recipient – Most common rejection seen in PK is endothelial cells Central trephine cut rejection observed in apprx 20% of low-risk cases – from 3500 cells/mm2 to 1200 made ’ – Repeated PK s increase chance that the graft will – this single layer spreads out: lacks mitosis be rejected • High density mitochondria : 90% pump – DALK can avoid risk of endothelial rejection with similar optical results as PK • Lenses produce reversible polymegathism Full thickness block Sutures create an Smooth Surface with only of tissue removed just irregular surface endothelial disease to get to the endothelium with astigmatism and blurring SCLAFANI

Deep Anterior Lamellar Keratoplasty (DALK) Abnormal Changes to the Endothelium

• Indicated for patients with • Endothelial cells become more irregular – • Cells secrete collagen – Corneal scars towards Descemet’s – Corneal stromal dystrophies causing multilamination – Basically any pathology that spares the = guttata endothelium • This breaks down the • Contraindicated barrier function and results in stromal and – Bullous keratopathy epithelial edema – Fuch’s

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Fuch ’s Dystrophy Fuch ’s Dystrophy: Guttata Fuch ’s Dystrophy

• Endothelium: • Patient symptoms vary with degree of guttata – acts as both a barrier and pump function and compromised pump function – responsible for maintaining corneal transparency • Moderate guttata by reducing corneal hydration – may affect visual function • Fuch ’s: – may result in light scatter (haloes) – typically noticed upon waking – occurs bilaterally, • With increased disruption to the pump: – AD inheritance, – vision decreases – females 3x more likely to develop condition – potential development of bullous keratopathy

Fuch ’s Dystrophy: Guttata

• Corneal guttata Healthy endo: Cornea Thin and clear Endo dropout: Cornea swells, mild vision loss – excessive accumulation of abnormal endo secretions is associated with the disease process – usually first noticed in the central cornea in the patients 30 ’s and 40 ’s – corneal physiology is affected adversely by interference with pump action – guttata appear as small refractile “drops ” on the Severe swelling, blisters on surface, Va drops, pain Chronic swelling, surface scarring corneal endo

Normal Endothelial Mosaic Stages of Fuch ’’’s Dystrophy

Fuch ’s Dystrophy: Guttata Fuch ’s: Bullous Keratopathy

• closer inspection with specular reflection reveals an “orange peel-like ” dimpling of the endo • with the decreased pump function, the overlying stroma becomes edematous • long standing corneal edema may result in corneal scarring and RCE BS – Pre-Op

Fuch ’’’s Dystrophy Endothelial Cell Count: 545 cells/mm

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DMEK (Descement Membrane Fuch ’s Dystrophy: Treatment DLEK Endothelial Keratoplasty) • Treatment in early stages: • Procedure has: • Recipient cornea is stripped of its Descemets – usually palliative with the goal of improving – minimal affect on refraction, membrane and endothelium implanted tissue consists of only the donors comfort and function – provides rapid visual recovery and – Descemets and endothelium – hyperosmotics at bedtime (e.g. muro 128 – maintains structural integrity of the cornea. ointment) may help reduce epithelial corneal – in comparison, DSAEK has implanted tissue consisting of posterior stroma, Descemets and edema in the morning endothelium – bandage CL can be used in the presence of bullous – implantation of similar tissue “components” keratopathy without additional posterior stroma has resulted improved visual function and recovery

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DLEK Surgery: Split Thickness Surgery to replace DMEK (Descement Membrane Fuch ’s Dystrophy: Treatment only the diseased tissue Endothelial Keratoplasty) Recipient tissue • When visual function deteriorates to the point patient removed • Compared to DSAEK, DMEK may have better clinical is unduly affected, surgical options are considered potential with 75% patients obtaining 20/25 or better including: within 1-3 months DSAEK 38-100% patients get 20/40 or better after 6 penetrating keratoplasty (PK) – – Scleral incision, deep months – DLEK surgery (deep lamellar endothelial keratoplasty) or corneal pocket, and Just endothelium on posterior – PK has 40% patients 20/40 or better after 1 year stromal disc removed from pocket – newer DSAEK (Descemet Stripping Automated Endothelial endothelium trephined • Visual recovering quicker with DMEK with many Keratoplasty) with Terry Trephine or cut with Cindy Scissors patients having good vision 1 day post op and best – Latest DMEK (Descemet Membrane Endothelial visual recovering by 1-3 months Keratoplasty) Donor tissue placed – DSAEK slower visual recovery and PK the slowest into recipient • Fuch ’s is leading reason for PK ’s in developed • Additionally, may have reduced endothelial cell lost countries post surgery Endothelium replaced with no sutures, supported by air bubble in anterior chamber. 47 Surface remains smooth with no astigmatism

DLEK DSAEK

• Recipient cornea is stripped of its Descemet’s • DLEK refined to DSEK and now DSAEK: membrane, endothelium and posterior stroma – compared to DLEK only Descement’s membrane and • There is transplantation of the posterior stroma endothelium is stripped and implanted in and endothelium of the donor cornea through a DSEK/DSAEK. small incision • DSEK vs. DSAEK: • Results in improved: – DSEK has the donor lamellar disc created manually – DSAEK facilitated by the use of a blade microkeratome – endothelial function, CORNEAL DEGENERATIONS which cuts the donor interface with the corneal – corneal clarity and button mounted in an artificial anterior chamber – restoring useful vision.

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6 5/20/2014

Keratoconus Keratoconus: Diagnosis Keratoconus

• Ectatic corneal dystrophy: • Keratoconus tends to progress over 7-8 years – tends to be bilateral, and then stabilizes – maybe asymmetric, and • Severity is variable b/w patients and is often – generally manifests in the 2nd or 3rd decade. asymmetric • Likely a multigenic disease: • Thinning can be extensive: – complex mode of inheritance (sporadic, AD and AR reported) and – resulting rupture in Descemet ’s membrane – manifestation likely involving environmental • triggers a sudden influx of aqueous into the cornea factors. (Hydrops)

Keratoconus Keratoconus Keratoconus-Fleischer ’s Ring

• Proposed etiology: – increased enzyme activities and decreased levels of enzyme inhibitors result in toxic by-products • destruction of the normal corneal matrix resulting in thinning and scarring.

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“““ ””” Keratoconus: Diagnosis Central Nipple Keratoconus OU Keratoconus-Corneal Thinning

• SLE findings include: – central corneal thinning, – Fleischer’s ring, – scarring at the level of Bowman’s layer or anterior stroma, and – vertical striae (Vogt’s lines). • Common refractive or topographic effects include: – irregular astigmatism and – poor best-corrected visual acuity with specs

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Keratoconus-Vertical Striae INTACS FOR KCN Collagen Cross Linking

• Clinical outcomes seem to follow a reproducible time course after treatment: – visual acuity and corneal steepness worsen over the first month – resolution to baseline by 3 months with continued improvement thereafter • Several studies have evaluated the use of CXL in the pediatric population (the most likely group to require a transplant) – recommended as a treatment to stabilize the cornea and to limit the progression of the condition

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Keratoconus Treatment The Future is Here! Keratoconus-Hydrops

• DALK • Collagen crosslinking of riboflavin and UVA- • Symptoms include: • Intacs: – sudden decrease in best corrected vision, Arclike PMMA segments designed to be surgically inserted light – – foreign body sensation or pain into deep corneal stroma to flatten the central cornea – Thought to strengthen the corneal collagen matrix – Indicated for mild to moderate keratoconus with a clear and stabilize the cornea • Signs include: optical zone and contact lens intolerant – conjunctival hyperemia/redness, – May delay or eliminate the need for keratoplasty although – Stops the progression of the condition with the significant may remain potential of some reversal – prominent central or inferior corneal edema and – Refractive stability has been demonstrated up to 5 years – clouding along with conjunctival hyperemia post-op in several studies • Might become the standard therapy for Tends to be self-limiting – Does have FDA approval for the treatment of keratoconus • in the US progressive keratoconus – in 8-10 weeks the endothelial cells regenerate across the ruptured Descemet ’s membrane

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TREATMENT OF KERATOCONUS WITH INTACS C3-R Mechanism Keratoconus-Hydrops Treatment

UVA 370nm • May use hyperosmotics and antibiotics to • The goal is to improve topography: prevent secondary infections – lift the ectasia to reduce irregular astigmatism • PK ’s are indicated if resulting scarring limits – flatten the soft tissue to reduce the SE Riboflavin .1% correction of vision • These changes should improve the UCVA and increase contact lens or spectacle success. Corneal Collagen Biomechanical • The intention is not to cure the disease, but Crosslinking Stiffness rather to delay need for a corneal transplant. Stability SCLAFANI 72

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Hydrops Pellucid Marginal Degeneration Pellucid Marginal Degeneration

• Bilateral corneal disorder hallmarked by a • Subjective symptoms are visual secondary to a thinning of the inferior, peripheral cornea dramatic increase in against-the-rule astigmatism • Corneal thinning begins apprx 1-2 mm above the • Area of thinning is free of vascularization or lipid inferior limbus and is separated by an area of infiltration which differentiates this condition uninvolved, normal cornea between the thinned zone and the limbus. from Terriens marginal degeneration of Mooren’s ulceration • Acute hydrops maybe seen in the area of inferior thinning • Corneal mapping demonstrates inferior mid- • Commonly manifests b/w ages of 20-40 with no peripheral zones of corneal steepening at 4-8 apparent hereditary transmission and equal o’clock producing “butterfly wing-like” pattern gender distribution which is diagnostic

Pellucid Marginal Corneal Keratoconus-Scarring Pellucid Marginal Degeneration Degeneration

Penetrating Keratoplasty Pellucid Marginal Degeneration Pellucid Marginal Degeneration

• Management includes specs, CL and surgery • Spectacle correction is often satisfactory in the early stages due to the minimal degree of induced astigmatism • In more advanced stages, CL are the suggested mode of treatment • CL management can be difficult because of the high degree of ATR and asymmetrical astigmatism • Surgical intervention involves PK, a kidney-shaped PK or an inferior lamellar patch graft.

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Pellucid Marginal Degeneration Terrien ’s Marginal Degeneration Terrien ’s Management

• Need to make sure differentiate: • Degeneration often progresses in a – peripheral corneal melt secondary too collagen circumferential pattern vascular disease, • Perforation is usually only a complication of – Mooren ’s ulceration, trauma. – pellucid marginal degeneration, • Etiology poorly understood though chronic – dellen, etc. inflammatory skin conditions and autoimmune mechanisms maybe possible etiology factors.

Terrien ’s Marginal Degeneration Terrien ’s Marginal Degeneration Mooren ’s Ulcer

• Rare, bilateral, asymmetric disease of • A painful, relentless, chronic ulcerative unknown etiology. that begins peripherally and • Peripheral cornea, predominantly superiorly, progesses circumferentially and centrally. undergoes lipid deposition, vascularization, • It is idiopathic; occurring in absence of any opacification and stromal thinning leading to diagnosable systemic disorder that could be gutter formation, ectasia and eventual corneal responsible for the progressive destruction of perforation. Epithelium remains intact. the cornea (e.g. peripheral corneal melt secondary to RA).

Terrien ’s Marginal Degeneration Terrien ’s Management Mooren ’s Ulcer

• May occur at any age, though typically occurs • As most patients are asymptomatic, management • Mooren ’s divided into 3 distinct varieties: is largely supportive. in middle-aged males. – Unilateral Mooren ’s: painful progressive corneal • May suffer from periodic episodes of red, ulceration in elderly • The eyes are typically not injected and there is irritated eyes which are quickly resolved with ’ steroids (Pred forte, Lotemax) – Bilateral Aggressive Mooren s Ulcer: occurs in little if any pain, photophobia or anterior younger Px, progresses circumferentially than chamber reaction • Early refractive treatment includes: centrally in the cornea and – spectacles (polycarbonate), – Bilateral Indolent Mooren ’s Ulceration: occurs in • Increased regular and irregular astigmatism, – CL an option though difficult to fit due to irregular which may produce visual changes though astigmatism (RGP over piggyback), middle-aged Px presenting with progressive – and when vision uncorrectable surgical intervention peripheral corneal guttering in both eyes, with patients are usually asymptomatic. includes PK. little inflammatory response. 84

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Mooren ’s Mooren ’s: Management

• Pathophysiological mechanism remains unknown • Initial therapy includes intensive topical steroid Tx: but there is evidence suggesting an autoimmune Pred Forte hourly is association with cycloplegics (e.g. Homatropine 5%) and topical antibiotics (moxifloxacin). process. • Pulse oral therapy (Prednisone 60-100 mg daily) can be • Px typically present with redness, tearing, considered when topical therapy ineffective after 7-10 photophobia, but pain is the most outstanding days. feature. The pain is often incapacitating and may • If ulcer continues to progress, conjunctival resection be out of proportion to the inflammation. should be performed. • For those Px that continue to progress, • Maybe visual disruption secondary to associated immunosuppressive chemotherapy is required to halt iritis, central corneal involvement, irregular the progression. astigmatism due to peripheral corneal thinning. • After active ulceration halted, PK maybe performed.

Mooren ’s Ulcer

Mooren ’s Ulcer

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