9/11/2019

Not Your Average Dry Eye WHAT IS DRY EYE? Alison Bozung, OD, FAAO Bascom Palmer Eye Institute

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Dry Eye Dry Eye

• TFOS DEWS II, 2017 • Symptoms – “A multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular – Redness, burning, blurred vision, pain, tearing symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.” • Prevalence – Anywhere from 5-50% of individuals have symptoms of dry eye (TFOS DEWS II)

Thinkaboutyoureyes.com, https://medicaldialogues.in/new-delhi-20-people-develop-blur-vision-after-being-given-contaminated-avastin-injection/, https://www.lasikmd.com/blog/the-risks- that-come-with-rubbing-your-eyes, https://www.powerofpositivity.com/10-things-that-cause-eye-pain/ 3 4

Dry Eye Dry Eye

• Signs 1. Aqueous Deficient (ADDE) • Conjunctival injection, meibomian gland dysfunction, corneal and conjunctival staining, reduced tear prism, rapid tear break up, 2. Evaporative (EDE) corneal scarring and thinning 3. Mixed

Does that explain everything..?

https://www.eyedolatryblog.com/2011/12/patients-guide-to-dry-eye-syndrome_15.html, https://www.pharmaceutical-journal.com/eye-care/pharmacy-technicians-guide-blepharitis- managing-eyelid-inflammation/20203771.article?firstPass=false, 5 6

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Beyond your “Typical” Dry Eye

• Today’s Discussion: 1. Exposure Keratopathy 2. Ocular Graft Versus Host Disease 3. Neurotrophic Keratopathy

Craig JP et al. TFOS DEWS II report executive summary. Ocul Surf. 2017;15:802-812.

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What defines exposure keratopathy?

• Desiccation of the cornea occurring from inadequate eyelid closure or decreased blink frequency. EXPOSURE KERATOPATHY

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Clinical Assessment Causes of Exposure • • Examination findings The etiology behind exposure is variable, and management strategy should be individually tailored to the patient – Incomplete lid closure on natural or forced blink • Eyelid laxity – Inferior or central corneal • Ectropion – Floppy eyelid syndrome punctate erosions – Cicatricial – Aging changes – Ectropion or facial scarring – Senile ectropion – Paralytic – Snap back test • Proptosis – Loose lids – Thyroid eye disease – Prominent globe

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Eyelid Laxity + Floppy eyelids Involutional Ectropion

• Floppy eyelid syndrome • Horizontal laxity due to lateral or Researchgate.net – Do they favor one side to sleep? medial canthal tendon laxity Eyerounds.org – Is patient an eye rubber? – Sleep apnea? • Examination – Lax lower lid, poor apposition to Eyerounds.org the globe • Refer? – When topical lubricants do not provide • Refer? effective treatment – Horizontal tightening of lower lid – Horizontal eyelid tightening procedure Reviewofophthalmology.com Andrew Rong, MD 13 14

Cicatricial Ectropion Paralytic Ectropion (CN7 palsy)

• Shortening of anterior lamella leads • Loss of orbicularis tone to outward rotation • Examination • Co-morbid conditions – Upper or complete hemifacial weakness – Seen in eczema, dermatitis, thermal • Complete: lower motor neuron burns, scleroderma, etc • Upper spared: likely contralateral CVA (!)

• Management • Etiology – Treat underlying condition – Bell’s Palsy – Temporary tarsorrhaphy may be indicated – Vestibular Schwannoma – Likely cicatrix release and full thickness – Neurofibromatosis Flattening of nasolabial fold (NLF) skin grafting www.scielo.br – Infectious (Lyme)

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Paralytic Ectropion (CN7 palsy) Proptosis: Thyroid Eye Disease

• Medical management • Enlargement of extraocular Eyerounds.org muscles or orbital fat expansion – Generous lubrication causing proptosis, lid retraction – Tape lids closed at night – Monitor for improvement if Bell’s Palsy • Management – Generous lubrication Morancore.Utah.edu • – Orbital decompression for severe Surgical management exposure keratopathy or compressive – Gold weight optic neuropathy – Tarsorrhaphy – If possible, surgery better during non- active phase – LTS Audrey Ko, MD 17 18

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Proptosis: Prominent Globe Exposure Keratopathy: In Summary

• Long axial length or shallow orbits • Severity determines our management strategy

• Management Mehryar Taban, MD • Recognize when surgical intervention is the best step – Generous lubrication – If threatening corneal health, may • benefit from orbital decompression Early or mild exposure: treat with lubrication drops + ointments

• Moderate to advanced exposure: referral to oculoplastics

Weinberg DA1 19 20

What defines Graft Versus Host Disease?

• Complication of allogenic hematopoetic stem cell transplantation (HSCT) GRAFT VERSUS HOST DISEASE (GVHD)

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Why is stem cell transplantation done? Who gets GVHD?

• Cancer • 9,000 HSCT in US in 2016 – Leukemia, lymphoma, multiple myeloma • 30-70% of individuals • History of chemotherapy or radiation develop GVHD

• Blood disorders • 60-90% of individuals – Anaplastic anemia, sickle cell anemia, thalassemia, with cGVHD experience congenital neutropenia ocular symptoms

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Who gets GVHD? Who gets GVHD?

• Risk Factors • Risk Factors – HLA mismatched – HLA mismatched • Most important factor! – Unrelated donor

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Who gets GVHD? Who gets GVHD?

• Risk Factors • Risk Factors – HLA mismatched – HLA mismatched – Unrelated donor – Unrelated donor – Female donor – Female donor • Increased risk after pregnancy/birth – + Intensity of radiation or chemotherapy

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Who gets GVHD? Stem Cell Donations

• Risk Factors • Stem cell sources – HLA mismatched – Bone marrow tissue – Peripheral blood stem cells – Unrelated donor – Umbilical cord blood – Female donor – + Intensity of radiation or chemotherapy – + Age of donor OR host

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Graft Versus Host Disease

! Stem cell donations also contain: 1. The donor’s immune cells Helper and killer T-cells • Are GOOD! – Recognize and kill cancer cells • Are sort of BAD!

– They also may “recognize” the host’s tissue as foreign and dangerous. http://chemosabe-socks.blogspot.com/2013/07/graft-versus-host-disease.html?m=1

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Graft Versus Host Disease Graft Versus Host Disease Acute Acute Chronic • Within 1 week • Within 1 week • Within 2-3 months • Organ systems affected • Organ systems affected • Organ systems affected – Ocular – Dermatologic – Dermatologic – Pulmonary – Hepatic – Hepatic – Neuromuscular – Gastrointestinal – Gastrointestinal – Genitourinary • Treatment • Treatment + – Mucosal membranes – Systemic corticosteroids – Systemic corticosteroids • Treatment – Corticosteroids +

https://www.aao.org/eyenet/article/stepwise-approach-to-ocular-manifestations , immunosuppression agents healthdirect.com https://www.sciencedirect.com/science/article/pii/S108387911400398X 33 34

Graft Versus Host Disease Chronic • Within 2-3 months • Organ systems affected – Ocular – Pulmonary – Neuromuscular – Genitourinary OCULAR SIGNS OF GVHD – Mucosal membranes • Treatment Zeiser R, Blazar BR. Pathophysiology of Chronic Graft- versus-Host Disease and Therapeutic Targets. N Engl J – Corticosteroids + Med. 2017;377(26):2565-2579. immunosuppression agents

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Ocular GVHD Ocular GVHD

• Lymphocytic infiltration of • Lymphocytic infiltration of conjunctiva and lacrimal gland conjunctiva and lacrimal gland and accessory lacrimal and accessory lacrimal structures structures • Decreased conjunctival goblet • Decreased conjunctival goblet cell density cell density • Epithelial cell necrosis • Epithelial cell necrosis • Increased conjunctival • Increased conjunctival squamous metaplasia squamous metaplasia

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Ocular GVHD: Clinical Findings Ocular GVHD: Management Strategy

• Elevated inflammatory markers Preservative- • Corneal punctate staining Basic Topical

free lubricants Autologous Severe corticosteroids Eyelid repair • Mucin deficiency serum Warm • Aqueous tear deficiency compresses Hyfrecation Cyclosporine Bandage or • Conjunctival hyperemia + fibrosis Scleral contact Punctal Mild toModerate lenses Partial Occlusion Lifitegrast • Cicatricial entropion ModeratetoSevere tarsorrhaphy • Corneal thinning and ulceration

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GVHD : In Summary

• Communication is KEY – Don’t forget to communicate your findings with the patient’s oncologist! NEUROTROPHIC • Aggressive management EARLIER is BETTER. – Lack of intervention leads to permanent cicatricial changes KERATOPATHY – It’s hard to come back late in the game! (NK) • We can make a BIG difference in these patients’ lives.

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What defines neurotrophic keratopathy? Who gets NK?

Damage to V1 nerve • Degenerative disease • Herpetic keratitis characterized by corneal • Diabetics sensitivity reduction, • Trauma spontaneous epithelium breakdown, and impairment • Prior ophthalmic surgery of corneal healing. • Chronic topical ophthalmic medications • Corneal dystrophies

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Reduced epithelial Clinical Assessment mitosis + migration - Punctate epithelial • Clues: erosions – Punctate erosions, low tear prism, reduced tear break up Reduced - Poor epithelial – Dry eye that appears much worse than it feels Corneal healing Sensation Decreased blink rate - Recurrent epithelial • defects Reduced tactile corneal sensation - Stromal thinning – Cotton wisp (qualitative) – Floss (qualitative) Decreased - Corneal perforation reflex – Cochet-Bonnet (quantitative) tearing

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Mackie Classification Stage I • Diffuse corneal punctate staining • Hazy epithelium, neovascularization, scarring Stage II MANAGEMENT OF NEUROTROPHIC • Persistent or recurrent epithelial defect KERATOPATHY Stage III • Persistent epithelial defect • Stromal loss / ulceration, melt

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Stage I Neurotrophic keratopathy Stage II Neurotrophic keratopathy

Goal: Improve surface integrity Goal: close persistent defect and and avoid epithelial defect prevent ulceration or scarring

• Frequent PF artificial tears • Continue Stage I treatment • Aggressively manage any other • Autologous serum tears q2h ocular surface disease! • Bandage or scleral contact lenses • Consider early addition of: • Amniotic membrane application – Punctal plugs • Nerve growth factor – Autologous serum tears – Oxervate (cenegermin-bkbj, Dompé Pharmaceuticals)

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Stage III Neurotrophic keratopathy Neurotrophic Keratopathy

Goal: prevent further ulceration or • In general, close monitoring and early intervention is key perforation

• Full court press! • Maintaining compliance can be difficult due to decreased symptoms – until vision loss occurs. • Oral tetracycline • Partial or near-complete tarsorrhaphy • It is an exciting time to manage this condition – more new • Nerve growth factor nerve growth factor treatments likely coming down the pike! • Topical steroid use with extreme caution if inflammatory component

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Thank you!

[email protected] IG: all_things_eye

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