OcularGVHD - University of Louisville Ophthalmology

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Transcript OcularGVHD - University of Louisville Ophthalmology

Grand Rounds
Mark Mugavin M.D., MPH
University of Louisville School of Medicine
Department of Ophthalmology & Visual Sciences
8/21/2015
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.
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.
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
Exam
OD
OS
VA(cc, near):
20/20-2 +2.00
20/25 +2.00
Pupils:
4
4
2
2
No APD
IOP:
EOM
15
17
0
0
0
0
0
0
0
0
Exam
OD
OS
Anterior Segment
L/L
Madarosis
C/S:
Clear
Cornea:
AC:
I/L:
Vitreous:
DFE:
Few scattered SPK
Dry eye
Madorosis
Mild Palpebral Conjunctival
Hyperemia
Diffuse SPK,
Severe Dry Eye
No cell or flare OU
WNL OU
WNL OU
WNL OU
Clinical Photos
Clinical Video
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
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
Hematopoetic Stem Cell Transplants

Epidemiology
 Est. 20,000 performed annually in U.S.
 Top three indications: Multiple Myeloma, NonHodgkins 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
Graft vs Host Dx (GVD)



Acute
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
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
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
CD45+ Positive Staining of inflammatory T cells attacking lacrimal duct
of a 21 yo male with Chronic GVHD (Photo credit #3 Ogawa et al)
Ocular GVD

Clinical Symptoms
 keratoconjunctivits
sicca (#1)
 confluent areas of punctate keratopathy
 new onset dry, gritty painful eyes
 cicatricial conjunctivitis
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
Grading GVHD
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%
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
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
Literature Review
Scleral Contact Lenses


Large diameter, rigid, gas permeable lenses
designed to cover exposed ocular surface
Features
a)
b)
c)
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
Scleral Lenses
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
Evidence for Scleral Lenses


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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
Scleral Lenses
References
1.
Balasubramian et al. “Ocular Graft-Versus-Host-Disease: A Review” Eye and Contact Lens 2015; 0 1-7
2.
Lin X, Cavanagh H “Ocular manifestations of graft-versus-host disease: 10 years experience” Clinical
Ophthalmology 2015 July 3; 9 1209-1213
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)
4.
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
5.
“Transplant Activity Report 2008-2012” Health Resources and Service Administration Blood Cell Transplant
http://bloodcell.transplant.hrsa.gov/research/transplant_data/transplant_activity_report/index.html#numbers
6.
“Ocular Graft Versus Host Diease” BCSC Section 9: External Disease and Cornea American Academy of
Ophthalmology 2015
Additional Info