1. Grand Rounds Mark Mugavin M.D., MPH
University of Louisville School of Medicine
Department of Ophthalmology & Visual Sciences
8/21/2015 1 1

2. Subjective
CC: blurry vision OU HPI: 57 year old white female with a history of B Cell Acute Lymphoblastic Leukemia (ALL) s/p bone marrow transplant March 2015 currently admitted on BMT service with abdominal pain, diarrhea, malaise, palpable pruritic skin patches.

3. Subjective
Patient has noticed episodes of blurry vision more frequent in the morning and noticeable at distance
Episodes lasting approximately 2-3 hours a day since being admitted a week ago.

4. POH: presbyopia PMHx: ALL s/p transplant, Adult Polycystic Kidney Disease ROS: per hpi. No visual disturbance noted in months leading up to admission Medications: Tacrolimus, Solumedrol 2 mg per kg IV Allergies: NKDA Social: social alcohol, denies cigarettes or illicits

5. Exam VA(cc, near): 20/20-2 +2.00 20/25 +2.00 Pupils: 4 2 4 2 No APD
OD OS
VA(cc, near): / /
Pupils:
No APD
IOP:
EOM 5

6. Exam Anterior Segment L/L Madarosis Madorosis
OD OS
Anterior Segment
L/L Madarosis Madorosis
C/S: Clear Mild Palpebral Conjunctival Hyperemia
Cornea: Few scattered SPK Diffuse SPK, Dry eye Severe Dry Eye
AC: No cell or flare OU
I/L: WNL OU
Vitreous: WNL OU
DFE: WNL OU 6

7. Clinical Photos

8. Clinical Video

10. Additional Considerations
While on high dose solumedrol last 6 Glucose readings (139,186,169,248,263,229)
Differential Diagnosis
Graft vs Host Disease with Ocular Manifestations
Hyperglycemic Induced Refractive Error

11. Assessment and Plan
59 year white female s/p BMT for ALL currently inpatient for Graft Host Disease. positive rose bengal staining, minimal conjunctival hyperemia OS
Prescribed artificial tears (preservative free) every 2 hours while awake for active lubrication. Lacrilube at hours of sleep

12. Hematopoetic Stem Cell Transplants
Epidemiology
Est. 20,000 performed annually in U.S.
Top three indications: Multiple Myeloma, Non-Hodgkins Lymphoma, Acute Myelogenous Leukemia
1958 French Oncologist Georges Mathe Performed first BMT following nuclear accident in Yugoslavia
1950’s-1960’s Dr. Donnal Thomas often cited as pioneer of the field found matching related dogs critical to success. Leader of Fred Hutchinson Cancer Research Center (Seattle). Nobel Prize in 1990

14. Graft vs Host Dx (GVD) Acute Chronic
Classically defined as developing in first 100 days
Involves mucous membranes of mouth, intestinal tract, skin, liver
HLA Identical Siblings 19-66% vs Matched Unrelated 70-90%
Chronic
>100 days and onwards
Involves lungs, eyes, and intestines
HLA Identical Siblings 33% vs Matched Unrelated 64%
Most studies suggest incidence of 60-90% overall
chA-toe-me-um
Dem-at-A-she-us

15. GVHD Pathophysiology
Complex multistep process with 3 essential criteria:
a) Graft must contain immunologically competent cells
b) Host must possess transplantation antigens lacking in the graft which appear foreign, thereby stimulating donor T cells
c) Host must be incapable of mounting a reaction against the graft for a period of time sufficient to allow the graft cells to attack the host

16. Ocular GVHD
Donor T cells (CD 4/ CD 8) are stimulated through cytokines (IL1, IL2, interferon gamma, TNF-A) to attack the lacrimal glands, conjunctiva, and accessory tear glands
Aqueous deficiency can lead to diminished visual acuity, corneal ulceration, microbial keratitis
Formation of a conjunctival pseudomembrane associated with poor prognosis

17. CD45+ Positive Staining of inflammatory T cells attacking lacrimal duct of a 21 yo male with Chronic GVHD (Photo credit #3 Ogawa et al)

18. Ocular GVD Clinical Symptoms keratoconjunctivits sicca (#1)
confluent areas of punctate keratopathy
new onset dry, gritty painful eyes
cicatricial conjunctivitis

19. Assessing Ocular GVHD Slit Lamp Examination
Dye Staining of Conjunctiva, Cornea (Fluorescein, Rose Bengal, Lissamine green)
Assessment of tear film utilizing Schirmer test, chemical analysis, microscopy
Schirmer Test
5 mm or less diagnostic
6-10 mm with another organ impacted suggestive

20. Grading GVHD
Grade 1: Conjunctival hyperemia occurring on the bulbar or palpebral conjunctiva in at least one eyelid
Grade 1: Conjunctival hyperemia occurring on the bulbar or palpebral conjunctiva in at least one eyelid
Grade 2: Palpebral conjunctival fibrovascular changes occurring along the superior border of the upper eyelid or lower border of the tarsal plate < 25%

21. Grading GVHD
Grade 3: palpebral conjunctival fibrovascular changes involving 25 to 75% of at least one eyelid
Grade 4: > 75% involvement with or without cicatricial entropion

22. Management Most resources recommend a stepwise approach
1)Preservative Free Artificial Tears and Viscous Ointment at bedtime
2) Autologous Tears
3) Mucolytic agents (ex: 10% N-Acetylcysteine)
4) Punctual Plugs
5) Topical Corticosteroids
6) Cyclosporine A
7) Tacrolimus
8) Scleral Large Diameter Contact Lenses

23. Literature Review

24. Scleral Contact Lenses
Large diameter, rigid, gas permeable lenses designed to cover exposed ocular surface
Features
Rest on the conjunctival tissue overlying the sclera in a way that vaults the cornea and limbus
Contain post-lens fluid reservoir for continuous hydration
Protection of the cornea and conjunctivae from irritation caused by lid movement over the ocular surface

25. Scleral Lenses

26. Scleral Contact Lens
Patient with prominent Ocular GVD fitted with Scleral Contact Lens. Note the sub-epithelial scarring on the inferior paracentral cornea
Slit lamp view demonstrating the space present between the cornea and the contact lens

27. Evidence for Scleral Lenses
Retrospective study from Harvard(n=33) patients with Chronic GVHD that failed “conventional therapy” (Enrollment Dec 2002 to Feb 2005)
Fitted with Boston Scleral Lenses and basic assessment of satisfaction measured
97% reported less eye pain
94% reduction in photophobia
93% improvement in reading
Retrospective study from Harvard(n=33) patients with Chronic GVHD that failed “conventional therapy” (Enrollment Dec 2002 to Feb 2005)
Fitted with Boston Scleral Lenses and basic assessment of satisfaction measured
97% reported less eye pain
94% reduction in photophobia
93% improvement in reading

28. Scleral Lenses

29. References
Balasubramian et al. “Ocular Graft-Versus-Host-Disease: A Review” Eye and Contact Lens 2015; 0 1-7
Lin X, Cavanagh H “Ocular manifestations of graft-versus-host disease: 10 years experience” Clinical Ophthalmology 2015 July 3;
Ogawa et al. “International Chronic Ocular Graft-vs-Host Disease (GVHD) Consensus Group: Proposed Diagnostic Criteria for Chronic GVHD” Nature. Scientific Reports 3: Article 3419 (2013)
Pezzotta S, Rossi G, “A cross sectional study on vision-related quality of life in patients with Ocular GvHD Bone Marrow Transplantation 8 June 2015
“Transplant Activity Report ” Health Resources and Service Administration Blood Cell Transplant
“Ocular Graft Versus Host Diease” BCSC Section 9: External Disease and Cornea American Academy of Ophthalmology 2015

30. Additional Info