viral treatment for chronic anterior uveitis …
TRANSCRIPT
VIRAL TREATMENT FOR CHRONIC ANTERIOR
UVEITISZachary Willits, O.D.
Southern Oregon VA Rehabilitation Center and ClinicsResident 2020-2021
Financial Disclosure
I have no relevant financial or nonfinancial relationships in the products or services described, reviewed, evaluated or listed in this presentation
■ An investigation of the use of valacyclovir treatment for a rare case of recurrent iritis caused by herpes zoster particles within the anterior chamber.
■ Objective
– By the end of this presentation, you will be able to identify a possible cause of rare, recurrent iritis and feel confident with its initiation of treatment and future management.
Patient Case
■ 34 YOWM presents for an office visit with concerns of an iritis flare up
– Location: Left Eye
– Onset: 1 week ago – faster vs. previous episodes
– Duration: daily and constant
– Frequency: recurrent, last episode 10/2019
– Symptoms: blur, pain (5/10) when focusing, redness, worsening watering
– Relief: none
History
■ Personal Ocular:– Migraine aura w/o headache– Bilateral iritis ~2015– Bilateral Non-Granulomatous Ant. Uveitis ~06/2018– Non-Granulomatous Ant. Uveitis OS ~11/2018– Non-Granulomatous Ant. Uveitis OS ~08/2019– Non-Granulomatous Ant. Uveitis OS 09/2020
■ No ocular/systemic meds and unremarkable family ocular history
■ NKDA, no drugs/alcohol/tobacco use
■ Unremarkable medical history– H/O (-) ACE/RF/Syphilis/TB/HLA-B27 labs
Entrance Findings
■ Entering Uncorrected VA:
– OD: 20/20
– OS: 20/20
■ Entrance Tests:
– Pupils: PERRL, (-)APD
– EOMs: SAFE OU
– CVF: FTFC OD,OS
– CT @Dist. sc: Ortho OU
Anterior Segment
Lids:Cornea:Tear Film:Conj:Ant. Chamber:Iris:Angles:IOP: GAT @ 1505
Clear
Clear
Normal
Clear
Deep & Quiet
Flat, no holes
4x4
16mmHg
Mild UL and LL injection
Clear
Normal
2+ diffuse injection
2-3+ cells/flare, 1+ fibrosis from 6-11:00
4x4
16mmHg
OD OS
Posterior Segment
Lens: clear broken synechiaepigment
Vitreous: clear clearOptic Disc: 0.35r, pink/distinct 0.35r, pink/distinctMacula: flat/dry flat/dryVessels: normal normalPost. Pole: unremarkable unremarkablePeriphery: no h/b/t 360 no h/b/t 360
OD OS
Assessment and Plan
■ Recurrent Iritis OS– 5th occurrence (onset 09/2020)– Unremarkable previous labs for clear systemic cause
■ Plan:– Educate patient on findings and DWP prognosis, chronicity, and treatment options including
observation– Speak with co-managing OMD – recommended Famciclovir 500mg PO TID x 7 days OR Valacylovir
1000mg PO TID x 7 days, then Valacylovir 500mg PO QD for management■ Pt declined antiviral treatment– Begin Homatropine BID x 7 days OS then stop, Pred Acetate 1% QID x 7 days OS then taper BID OS
x 1 month– RTC 2 weeks for follow-up (pt unavailable for sooner appointment)
Uveitis
Anterior Uveitis
■ “Inflammation of the middle layer of the eye. Affected structures include the iris and adjacent tissue, specifically, the ciliary body.”
https://i.pinimg.com/originals/5b/4a/7f/5b4a7f7b0aedc5d43af2d1f247f9daac.jpg https://www.merckmanuals.com/-/media/manual/professional/images/anterior-uveitis-garg-high.jpg?thn=0&sc_lang=en
Acute Causes
1. Idiopathic– Most common
2. Autoimmune– HLA-B27-related: ankylosing spondylitis, arthritis, etc.
3. Trauma– Including post-surgical
4. Viral/Bacterial Infections– Lyme Disease, influenza, Chlamydia, adenovirus, etc
***NON-EXHAUSTIVE LIST OF CAUSES– WORK-UP/CASE HISTORY IS IMPORTANT***
Chronic Causes
1. JIA– Most commonly in young females
2. Fuchs heterochromatic iridocyclitis– Similar to JIA
3. Sarcoidosis– Most common in African Americans and those of Scandinavian descent
4. Herpes Simplex/varicella zoster
5. Syphilis
6. Tuberculosis
Diagnosis
■ Signs
– Most common: cells and/or flare in the anterior chamber, ciliary flush, keraticprecipitates (KP)
■ Fine KP, small non-granulomatous KP, granulomatous KP
– Less Common/Other: low IOP, fibrin, hypopyon, iris nodules, iris atrophy, iris heterochromia, iris synechiae, and band keratopathy
■ Symptoms:
– Acute: pain, redness, photophobia, excessive tearing, decreased vision
– Chronic: decreased vision, periods of exacerbation and remission
Critical Lab Tests
■ HLA-B27 for autoimmune
■ PPD or IGRA for TB
■ RPR, VDRL, FTA-ABS for syphilis
■ Chest x-ray or CT for sarcoid and/or TB
■ Lyme (usually in endemic areas)
■ Anterior chamber paracentesis for PCR testing for suspected viral cause
Treatment/Follow-Up
■ Cycloplegic: improve comfort, prevent synechiae
– Cyclopentolate 1% TID for mild-mod. Inflammation
– Atropine 1% BID-QID for severe inflammation
■ Topical Steroid w/ taper: control inflammation
– Prednisolone Acetate 1% q1-6h depending on severity of inflammation
■ Treat underlying systemic condition to avoid recurrence
■ Follow-up every 1-7 days in acute phase, 1-6 months when stable
– start steroid taper and once inflammation is resolved
– d/c cycloplegic once inflammation starts to improve
Additional Treatment Considerations
■ May need stronger drop or more frequent dosing for severe inflammation
■ Consider loading dose or FML 0.1% ointment at night
■ Treat secondary glaucoma or IOP spike as indicated– Avoid pilocarpine
Herpes Zoster
Etiology
■ Varicella zoster virus
– Likes to live within CN V; more common within V1 but can occur along V2 and/or V3
– Chicken pox in children
– Shingles in adults (reactivation of latent virus)■ T-cell mediated immune response
– Spread via direct contact with respiratory secretions or skin lesions
https://www.immune.org.nz/sites/default/files/VaricellaSquare.jpg
https://post.medicalnewstoday.com/wp-content/uploads/sites/3/2021/01/shutterstock_1600988488_slide.jpg
Chicken Pox Shingles
https://i.pinimg.com/originals/4a/95/8e/4a958ef8e6ae89804ce71c374d70673e.jpg
V1
V2
V3
Diagnosis
■ Typically diagnosed based on clinical presentation
– Skin redness, rash, and/or lesions that respect vertical midline
– Patients may report prodromal symptoms of general malaise, fever, and headache for up to 5 days before signs present
– CLASSIC: Hutchinson sign
https://healthjade.net/wp-content/uploads/2020/01/hutchinsons-sign-nose.jpg
Diagnosis
■ Ocular signs:– Conjunctivitis, episcleritis and scleritis, keratitis, uveitis, and/or elevated IOP
■ Lab Tests:– PCR testing
https://d45jl3w9libvn.cloudfront.net/jaypee/static/books/9789350252611/Chapters/images/107-2.jpghttps://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/VZV-keratitis/VZV-keratitis-LRG.jpg
Treatment
800mg PO 5x/day x 7-10day 500mg PO TID x 7 days 1000mg PO TID x 7 days
Recurrent Iritis due to HSV or VZV
■ Anterior chamber inflammation found in ~10% of patients with HZO
– Diagnosis is straightforward with skin lesions; more difficult in its absence■ May have more prodromal symptoms
■ Commonly may have iris atrophy, sectoral TIDs, and/or decreased corneal sensation
■ Key to diagnosis is anterior chamber paracentesis followed by PCR testing to confirm varicella particles
https://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10792-019-015/MediaObjects/10792_2019_1125_Fig3_HTML.jpg
https://www.researchgate.net/profile/Austin-Bach-3/publication/321974704/figure/fig1/AS:574036784291840@1513872442980/anterior-chamber-paracentesis-of-the-right-eye-following-an-intravitreal-injection.png
Current Pathophysiology Thought
Varicella/Simplex particles at sub-clinical levels reside in anterior chamber --> times of stress cause reactivation of particles --> recurrent episodes of uveitis
■ HSV more common in younger patients
■ VZV more common in older patients
Antiviral Treatment
■ Van der Lelji et. al. propose treating the anterior uveitis according to the most current methods (e.g. topical steroids with taper and cycloplegics) followed by a long steroid taper and prophylactic antiviral treatment
– Consider tapering steroids over 1-2 month period (e.g. BID x 1 month, then QD x 1 month)
– Acyclovir 400mg PO BID or Valacyclovir 500mg PO QD to reduce recurrence ■ Emmett Cunningham Jr., M.D., Ph.D recommends Valacyclovir as the drug yields 3-4x higher
circulating levels vs. acyclovir
– He also mentions topical acyclovir ointment, however it is difficult to obtain in the U.S.
Managing My Patient
■ Unfortunately the patient declined the use of oral medication due to anxiety and self-described PTSD involving the use of oral medication
■ He also stated, “absolutely no way is a needle going into my eye.”
■ Discussed likely cause of chronicity and to consider ant. chamber paracentesis with PCR testing, and prophylactic antiviral treatment in the future.
Importance
■ Strongly consider viral cause as differential diagnosis in cases of chronic or recurrent anterior uveitis with unremarkable traditional lab tests
– Consider ant. chamber paracentesis with PCR testing
■ As optometrists, YOU already know the treatment for the individual conditions....now combine them
■ May improve patient retention and remove need for referral, especially in patients who have difficulty with travel
Thank You to VA Doctors, Staff, and Student Interns
References
1. “Anterior Uveitis.” AOA.org, American Optometric Association, www.aoa.org/healthy-eyes/eye-and-vision-conditions/anterior-uveitis?sso=y.
2. “The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease, 7th Edition.” The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease, by Pa.) Wills Eye Hospital (Philadelphia et al., 7th ed., Lippincott, Williams & Wilkins, 2017, pp. 77-80, 340–346.
3. Agrawal, Rupesh V, et al. “Current Approach in Diagnosis and Management of Anterior Uveitis.” Indian Journal of Ophthalmology, Medknow Publications, Jan. 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC2841369/.
4. Onofrey, Bruce E., et al. Ocular Therapeutics Handbook. 4th ed., Wolters Kluwer, 2020. 5. Hoffman, Jeremy, and Allen Foster. “Viral Diseases of the Eye.” Community Eye Health
Journal, vol. 33, no. 108, 2020, pp. 68–70. 6. Cunngingham Jr., Emmet T. “Diagnosing and Treating Herpetic Anterior Uveitis.”
Ophthalmology, vol. 107, no. 12, 1 Dec. 2000, pp. 129–130. 7. Lelij, Allegonda Van der, et al. “Anterior Uveitis with Sectoral Iris Atrophy in the Absence of
Keratitis.” Ophthalmology, Elsevier, 31 May 2000, www.sciencedirect.com/science/article/abs/pii/S0161642000001159.
QUESTIONS?
Iris Lesions: A Cyst-ematic Approach
By Natalie Kulaga, O.D.
Disclosures
I have no financial conflicts of interest to disclose.
Special Thanks
Dr. Lindsay KleinschmitDr. Anna Wells
Dr. Chad GosnellDr. Len Koh
Dr. Jeffrey UrnessDr. Allison Makadia
Dr. Megan McChesney
Course Objectives
The goal of this lecture is to help clinicians identify which lesions are harmful or need treatment, versus lesions that can be safely monitored in order to improve patient outcomes.
Background on Iris Lesions
- Found in all races but mostly Caucasians- Demographics (Shields Study) of 3680 cases from the U.S:
- 96% Caucasian- 2% African American- 1% Hispanic- <1% Asian- <1% other races
- Wide range of ages at presentation- 12% of children <20 years old- 21% of young adults 21-40 years old- 36% adults aged 41-60- 31% of seniors 61+
Types of Iris Lesions
1) Cystic Lesions (21%)a) Come from either the stroma or pigment epithelium
i) Iris stromal cysts(1) Often require treatment or removal
ii) Iris pigment epithelium cysts*(1) Don’t usually require treatment and tend to
remain stable
2) Solid Lesions (79%)a) Melanocytic
i) Nevus (melanocytoma)*ii) Lisch noduleiii) Melanoma*
b) Nonmelanocytic (uncommon)i) Choristomatous ( = normal cells in an abnormal
location)ii) Vasculariii) Fibrousiv) Neuralv) Myogenicvi) Epithelialvii) Xanthomatousviii) Metastaticix) Lymphoidx) Leukemicxi) Secondaryxii) Non-neoplastic simulators
* = most common clinically
Cystic Lesions
Stromal Cysts
- Derived from front (stromal) part of iris- Most often congenital, found in pediatric patients
- Arise during embryonic development- Comprise 16% of iris cysts in children
- Most likely to deform iris and push the it forward- Bulge in iris can trigger the clinician to
worry about a tumor- Worse visual prognosis than with
epithelial cysts- Can be confused for a melanoma, especially if
it's heavily pigmented and looks like a nodule
- Can enlarge and rupture!- Pay attention in newborn infants: can
grow in just a few weeks and cause photophobia and buphthalmos/pediatric glaucoma
buphthalmos
Iris Pigment Epithelial Cysts
- Most common type- Rarely symptomatic, don’t really affect vision - Usually benign, translucent with brown specks- Often multifocal and bilateral- Sometimes detach and float freely in the anterior
chamber or the vitreous
- Classification (from most common to least): - Peripheral (73%)- Midzonal (21%)- Central (3%)- Dislodged (3%)
Epithelial Downgrowth Cysts
1) When surface epithelial cells get “transported” inside the eye
- i.e. trauma or surgery- Can form immediately, or years after
2) If cells inside the eye differentiate incorrectly into epithelial cells
- Usually benign if contents remain enclosed- Harmful if burst open- Often proteinaceous fluid inside (not
entirely clear contents)- Can grow aggressively and quickly like a tumor- In young children:
- Sometimes cover the pupil and cause amblyopia
Case: 94 year old male- Presented for routine eye exam; no
complaints- IOP normotensive, PERRLA - H/o malignant melanoma L arm
- Lesion first noted 08/27/2015 on routine exam- ~2.2mm in size, rounded edges- Brown but not opaque; transilluminates on slit
lamp exam
94 yo M, continued
- Gonioscopy: (Images A & B)
- Cystic/fluid filled lesion with defined edges, displacing iris posteriorly.
- Not intrinsic to iris or angle @7:00. - No visible dispersed pigment
- Referred to Casey Eye Institute for evaluation:- “UBM: relatively large, thin walled appearing
cyst in the angle, does not appear to involve the ciliary body. No other lesions noted.”
- “Consistent with a dislodged iris pigment epithelial cyst”
- Recommended to follow yearly w/ routine exams
A
B
Anterior Segment OCT of iris cyst in a 94 yo white male
Solid Lesions: Melanocytic
Pigmented nevus Melanocytoma Melanoma with angle involvement
Non-pigmented nevus (causing corectopia) Lisch nodules
Iris melanoma (causing corectopia)
Images from AAO.org
Freckle vs. Nevus vs. Melanocytoma?
A. Freckle: a. Can be either solitary or multifocal, and rests just on the surface
of the iris stromal surface. b. Usually <2mm in diameter.
B. Nevus: a. Penetrates deeper into the stroma, causing distortion of stromal
tissue. b. Often causes corectopia/ectropion
C. Melanocytoma: a. Subset of iris nevusb. Darkly pigmented, dome-shaped lesion with little to no ectropion. c. “Mound of black sand” d. Can seed into the angle or onto the iris stroma
All are benign!
Images from Mann-Grandstaff VAMC
Iris freckle
Iris nevus
Iris Melanoma
- Located in inferior quadrant most often
- Mean diameter: 6.2mm- Mean depth/thickness: 2.3mm- Partially or completely pigmented in
90% of cases- Metastasis in 5% at 5 years, 9% at
10 years, and 11% at 20 years- Main predictive factors for metastasis:
- 1) extraocular extension- 2) elevated intraocular pressure
Melanoma with diffuse growth pattern
B-scan of an iris melanoma
Circumscribed, tan/light iris melanoma
Determining risk: Nevus→ Melanoma
A age: younger than 40 years old
B blood: presence of a hyphema*
C clock hour of mass inferiorly
D diffuse growth pattern*
E ectropion
F feathery margins
*The most powerful factors
- Tumor seeding into the anterior chamber angle and onto the iris stroma are also important.- Transformation of suspicious iris nevus to melanoma occurred in 4% by 10 years and 11% by 20
years.
Confirming the Diagnosis
Properly identify location and origin:
1. Thorough historya. Intraocular foreign bodies? Past surgeries? b. If a cyst appears suddenly, worth asking about prostaglandin analogs (latanoprost, bimatoprost,
etc): they can make cysts bigger2. Complete exam:
a. Gonioscopyb. Anterior segment imaging
Good rule of thumb: Whatever method you use, be able to scan the whole cyst/lesion so there are no surprises
Lesions with solid components to it can be further evaluated with MRI or biopsy to confirm malignancy
Imaging StrategiesA. Anterior segment OCT
- Helpful to track size over time: repeatedly scanning the same area
- Downfalls: dark irides or large/dark cysts can block to signal
A. High-resolution ultrasound biomicroscopy (UBM)
- Good for visualizing thin walls and hollow cavities (fluid-filled lesions) or opaque and solid masses (malignancies)
- Scans around the peripheral iris/angle:- picks up what OCT can miss
- Helps surgeons with planning surgery: - extent of cyst and the type of tissue before
removal- Downfalls: not easily accessible in most offices, needs
a water bath immersion, and longer/more skill to acquire images
UBM of iris melanoma
UBM of normal A/C structures
Iris Melanoma
Iris Nevus
Iris Pigment Epithelial
Cyst
AS-OCT Anterior Segment Photo UBM Complications
A. Visual/Oculara. Iritis, angle closure/glaucoma
i. Pigment dispersion syndrome, plateau iris b. Focal cataract, lens subluxation, corneal edemac. Pain, blurred vision, photophobia
d. Amblyopia (in children)
B. Systemic a. Metastasis
i. Primary site is most often: 1. Lung2. Colon3. Breast4. Kidney5. Skin
b. Death (rare)Iris cyst causing corneal edema
Pupil distortion, partial angle obstruction, and corneal disruption due to large cyst
Treatment/Management
Non-malignant cysts/lesions:
A. Can usually just be observed
A. Monitor unless causing other issues in the eye: a. High IOP/angle occlusionb. Leakage causing inflammationc. Rubbing against the cornea causing endo
decompensation
A. When removal is indicated:a. All material exposed to the must be
removedb. Some require multiple removals to get them
outi. Risk of growing back more
aggressivelyii. Why thorough imaging/plan for
removal is crucial
Removal Strategies:
1. Partial lamellar iridocorneal trabeculectomy- Remove the areas the cyst is touching- Avoid breaking the cyst itself
2. Cyst drainage/deflation and injection with alcohol- Subsequently treated with endolaser to kill the
remaining epithelial cells- Then cryotherapy at the edge by the limbus to
sterilize those cells- Some cysts can be completely frozen (if peripheral
enough)
3. Stromal cysts in children:- Fine-needle aspiration- Photocoagulation (with Nd: YAG or Argon laser)- Excision (last resort)
Treatment/ManagementIris melanomas/malignancies
A. Surgical resectiona. If tumor is confined to 3-4 clock hours, and without
seeding
A. Plaque radiotherapya. If tumor is large and with seedingb. Keeps eye intact w/o entering anterior chamberc. If plaque covers cornea, amniotic membrane is placed
first to protect cornead. Iodine “seeds” placed in the plaque for targeted
radiation
A. Enucleationa. If there is uncontrollable secondary glaucoma or painb. Rare
A. CyberKnife radiosurgery?a. Delivers focal radiation to the lesion siteb. Non-invasive, single session treatment optionc. Comparable outcome to brachytherapyd. Good visual outcome in preliminary studies
CyberKnife equipment
Melanoma before CyberKnife treatment (A, B)
Melanoma regression 2yrs after CyberKnife treatment
49 year old female with 8x4x3mm iris melanoma (g). Peritomy (a) was performed prior to amniotic membrane placement onto cornea (b) prior to placement of plaque and suturing in place (c). Conjunctiva/Tenons was then placed over the plaque and sutured in place (d). Temporary tarsorrhaphy was performed during treatment (4 days). Image (h) 4 months following brachytherapy.
g
h
a b c
d e f
Brachytherapy
Prognosis and Outcomes
- Complications following resection:- Hyphema, vitreous prolapse, dislocated lens, cataract, iridocyclitis, macular edema, secondary glaucoma, and retinal
detachment- Most primary tumors of the iris are benign
- Iris melanomas usually have better prognosis than ciliary/choroidal melanomas- Generally good survival rate- Young adults tend to have a smaller melanoma basal dimension and a lower rate of tumor-related metastasis and death
than do older populations- Mortality rate: ranges from 0%-11%, depending on:
1. Cell type2. Presence/absence of metastases3. Ciliary body involvement
a. If ciliary body is not involved, mortality rate is 0%-3%- Metastasis:
- Occurs in 2%-10% of all iris melanomas- Higher rate of metastasis with ciliary body involvement
*A significant correlation between poor visual outcome and poor preoperative visual acuity and preoperative irradiation has been observed*
References1. American Academy of Ophthalmology. 2020. Identifying And Managing Iris Cysts. [online] Available at: <https://www.aao.org/eyenet/article/identifying-and-managing-iris-cysts>
2. Conway RM, Chua WC, Qureshi C, et al Primary iris melanoma: diagnostic features and outcome of conservative surgical treatment British Journal of Ophthalmology 2001;85:848-854
3. Eyewiki.aao.org. 2021. Iris Cysts - EyeWiki. [online] Available at: <https://eyewiki.aao.org/Iris_Cysts#Secondary_complications>
4. Eyewiki.aao.org. 2021. Iris Melanoma - EyeWiki. [online] Available at:
<https://eyewiki.aao.org/Iris_Melanoma#:~:text=Iris%20melanoma%20is%20the%20most,colored%20iris%20versus%20non%2DCaucasions>
5. Eyewiki.aao.org. 2021. Ultrasound Biomicroscopy - EyeWiki. [online] Available at: <https://eyewiki.aao.org/Ultrasound_Biomicroscopy>
6. Finger PT. Plaque radiation therapy for malignant melanoma of the iris and ciliary body. Am J Ophthalmol. 2001 Sep;132(3):328-35. doi: 10.1016/s0002-9394(01)01007-8. PMID: 11530044.
7. Gan Yuen Keat, Syed Shoeb Ahmad, Suresh Subramanian, Shuaibah Abdul Ghani, Amir Samsudin. Large Non-traumatic Iris Cyst. American Journal of Medical Case Reports. Vol. 4, No. 6, 2016, pp
218-220. http://pubs.sciepub.com/ajmcr/4/6/9
8. Geisinger Commonwealth School of Medicine, 2019. Pediatric Iris Cyst. [image] Available at: <http://morancore.utah.edu/section-06-pediatric-ophthalmology-and-strabismus/pediatric-iris-cyst/>
[Accessed 28 May 2021].
9. Hau SC, Papastefanou V, Shah S, Sagoo MS, Restori M, Cohen V. Evaluation of iris and iridociliary body lesions with anterior segment optical coherence tomography versus ultrasound B-scan. Br J
Ophthalmol. 2015 Jan;99(1):81-6. doi: 10.1136/bjophthalmol-2014-305218. Epub 2014 Aug 4. PMID: 25091953; PMCID: PMC4283679.
10. Keat, Gan Yuen, et al. "Large Non-traumatic Iris Cyst." American Journal of Medical Case Reports 4.6 (2016): 218-220.
11. Liu W, Kim J, M, Young B, K, Nath R, Chen Z, Decker R, H, Astrahan M, A, Pointdujour-Lim R: Novel Eye Plaque Designs for Brachytherapy of Iris and Ciliary Body Melanoma and the First Clinical
Application. Ocul Oncol Pathol 2019;5:220-228. doi: 10.1159/000493269
12. Lois N, Shields CL, Shields JA, Mercado G. Primary cysts of the iris pigment epithelium. Clinical features and natural course in 234 patients. Ophthalmology. 1998 Oct;105(10):1879-85.
13. Moshirfar M, Hall MG, Ronquillo Y. Epithelial Downgrowth. [Updated 2021 Jan 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK558996/
14. New York Eye Cancer Center. 2021. Iris Cysts » New York Eye Cancer Center. [online] Available at: <https://eyecancer.com/eye-cancer/conditions/iris-tumors/iris-cysts-2/> [Accessed 28 May 2021].
15. Primer, D., 2021. Differentiating Iris Pigmented Lesions: A Primer. [online] American Academy of Ophthalmology. Available at: <https://www.aao.org/eyenet/article/differentiating-iris-pigmented-lesions>
[Accessed 28 May 2021].
16. Schmelter V, Heidorn S, Muacevic A, Priglinger SG, Foerster P, Liegl R. Robotic assisted CyberKnife radiosurgery for the treatment of iris melanoma. Sci Rep. 2021 Mar 11;11(1):5685. doi:
10.1038/s41598-021-84290-x. PMID: 33707492; PMCID: PMC7952409.
17. Shields CL, Shields PW, Manalac J, Jumroendararasame C, Shields JA. Review of cystic and solid tumors of the iris. Oman J Ophthalmol. 2013;6(3):159-164. doi:10.4103/0974-620X.122269
18. Wendy Huang, N., 2021. Pediatric Glaucoma: A Review of the Basics. [online] Reviewofophthalmology.com. Available at: <https://www.reviewofophthalmology.com/article/pediatric-glaucoma-a-review-
of-the-basics> [Accessed 28 May 2021].
Jasmeen Bhangu, OD
Cornea and Contact Lens Resident 2020-2021
Email: [email protected]
Specialty Eyecare Group - Bellevue | Kirkland | Seattle, WA
PULLING THE PLUG ON DRY EYE: MANAGING THE
SPECTRUM OF DRY EYE DISEASE
DISCLOSURES • The presenter, Dr. Jasmeen Bhangu, OD, has no
financial interest or relationship with any companies, products, or pharmaceuticals mentioned in this presentation.
COURSE DESCRIPTION
This course presents a case of a patient referred in for management of refractory dry eye disease (DED) and provides an overview of the multifactorial nature and treatment of DED.
COURSE OBJECTIVES
• By the end of the presentation, attendees will be able to:
1. Define the multifactorial nature of dry eye disease
2. Differentiate etiological factors in dry eye disease based on subjective and objective examination data
3. Identify and utilize appropriate diagnostics in the management of dry eye disease
CASE PRESENTATION
• 46-year-old Asian Female referred for dry eye evaluation and possible treatment with punctal plugs
• History of chronic, refractory dry eye
• Referring optometrist prescribed topical immunomodulating therapy: Restasis BID OU
• Patient self-d/c as she wasn’t noticing a difference but reported aggressive lubrication with PFATs
• Additionally, patient reported trying lid scrubs with poor compliance
• Patient complaining of “constantly changing glasses prescription” and “vision that doesn’t ever feel quite right” in addition to increasing contact lens intolerance
RELEVANT EXAMINATION FINDINGS
• Presenting distance VAs:
• OD/OS/OU: 20/40
• All other entrance testing unremarkable
• Posterior segment: unremarkable
• Anterior segment:
• Lids: Significant and multiple inspissated glands OU,
• Marx Line: moderate UL/LL OU,
• Lid wiper: mild OD, moderate OS UL/LL
• Lashes: Grade 2 squamous blepharitis UL OU
• Bulbar conjunctiva: inferior grade 1 lissamine green staining OD and N/T grade 1 lissamine green staining OS, and moderate temporal conjunctivalchalasis
• Palpebral conjunctiva: grade 2 papillae LL OU with scattered inf concretions OU
• Cornea: Diffuse, grade 4 SPK OU, reduced sensitivity OU
• Korb-Blackie Lid Light Test: negative OU
• Inflammadry: strong positive OU
CORNEAL ESTHESIOMETRY
• What are we evaluating?
• Function of ophthalmic branch of trigeminal nerve
• Qualitative method: cotton wisp
• results will be either (+) or (-) corneal sensitivity
• Quantitative method: Cochet-Bonnet esthesiometer
• The shorter the length, the more decreased corneal sensation
• Nylon filament fully extends to 6 cm and retracts into device
COCHET-BONNET CORNEAL ESTHESIOMETER
https://www.researchgate.net/figure/The-Cochet-Bonnet-esthesiometer_fig2_259115435
NO REFRACTION FOR YOU!
DRY EYE IS MULTIFACTORIAL
“Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”10
AQUEOUS DEFICIENT OR EVAPORATIVE?
• TFOS DEWS II concluded that while these subtypes are distinct, they are still part of a spectrum of disease, rather than being distinct pathophysiological processes.
• Determining the predominant underlying etiology is useful in directing treatment strategies1
ETIOLOGICAL FACTORS
Korb, et al. AAO 2020. “A New Clinical Description and Science Based Approach Provides Effective Treatment”
LID WIPER EPITHELIOPATHY
(LWE)
• The lid wiper region of the eyelid is characterized as stratified squamous epithelium on the margin of the palpebral conjunctiva
• Li, et al. concluded LWE was associated with decreased tear-film stability, contact lens wear, lid anatomy, and LIPCOF (lid parallel conjunctival folds)2.
Efron, Nathan, et al. “Lid Wiper Epitheliopathy.” Progress in Retinal and Eye Research, Pergamon, 14 Apr. 2016, www.sciencedirect.com/science/article/abs/pii/S1350946216300131.
3Varikooty, Jalaiah. “What Is Lid Wiper Epitheliopathy? .” Clspectrum.com, CL Spectrum , 1 Nov. 2015, www.clspectrum.com/issues/2015/november-2015/what-is-lid-wiper-epitheliopathy.
LINE OF MARX
• Marx’s line is visualized as a thin strip, separating the keratinized cutaneous epithelium from the non-keratinized conjunctival epithelium3
https://www.clspectrum.com/issues/2015/november-2015/what-is-lid-wiper-epitheliopathy
MORPHOLOGICAL CHANGES SUGGESTING MGD
• In patients with tear film instability and meibomian gland dysfunction (MGD), Marx’s line (ML) is often displaced anteriorly.5
• Anterior displacement of Marx’s line may be used as a rapid screening for meibomian gland function6
MEIBOMIAN GLAND DYSFUNCTION
• Prevalence likely greater than we think
• Some estimate a prevalence of up to 68%, with increasing prevalence with every decade of life.10
• Meibomian gland dysfunction is defined as six or fewer functioning lower lid meibomian glands (Korb et al, 2014)
• 86% of dry eye has meibomian gland dysfunction (MGD) as an underlying cause7
KORB-BLACKIE LID LIGHT TEST
• Positive lid seal (light escaping the closed lids) indicates a form of nocturnal lagophthalmos
• Tends to be greater centrally
• Transilluminate across gently closed lids and observe whether light escapes
8Morrow, Azinda. “What You Can Learn from Lids.” What You Can Learn From Lids, Review of Optometry, 15 Jan. 2019, www.reviewofoptometry.com/article/what-you-can-learn-from-lids.
ADDITIONAL TESTING
• Consider blood testing for autoimmune conditions in severe and refractory dry eye disease
• SLE, RA, Sjogren’s associated with DED
• Commonly ordered blood tests ordered in management of dry eye
• RF
• ANA
• Sjogren’s antibody test (SS-A, SS-B)
• Thyroid peroxidase antibodies (TPO)
VALIDATED TREATMENT OPTIONS
• Internal/external thermal pulsation treatment: Lipiflow, iLux, TearCare
• hot compresses provide external heat only
• Topical pulsed steroid therapy
• Topical immunomodulating therapy with cyclosporine or lifitegrast
• Autologous serum drops
• Amniotic membranes or amniotic membrane drops
• Punctal plugs – consider only after determining whether inflammation is present and treating in true tear deficiency
• Oral antibiotics (low dose doxycycline, minocycline)
• Bandage and scleral contact lenses
OUR PATIENT – WHAT DID WE DO?
• Initiated topical immunomodulating therapy with Cequa BID OU
• In-office lid exfoliation to debride the lid margins
• Recommended thermal pulsation treatment to address MGD
• Recommended at-home therapies: lid scrubs QD and hot compresses
• Defer refraction until improvement in ocular surface staining observed
• At follow up, visual acuity improved to 20/20 with existing spectacle lenses
IMPROVE SURGICAL OUTCOMES
• A study of 124 eyes of 124 patients randomized to control group or Lipiflow group11
• Control arm: no treatment
• Study arm: Lipfilow treatment
• Design: subjective and objective measurements
• meibomian gland (MG) evaluation, MG atrophy, degree of gland expressibility, and quality of gland secretions, tear film break-up time (TBUT), corneal staining score, and tear film lipid layer thickness (LLT).
• Ocular Surface Disease Index (OSDI) and Dry Eye Questionnaire (DEQ) were also assessed pre-and post-op
• Conclusions: subjective and objective improvement in meibomian glands yieldling liquid secretions (MGYLS) post-op in treatment group while control group continued to decline, suggesting ocular surgery contributes to MG atrophy and worsening of DED.
REFERENCE
1. Winebrake, James P., et al. “The TFOS Dry Eye Workshop II: Key Updates.” EyeNet Magazine, American Academy of Ophthalmology, Nov. 2017, www.aao.org/eyenet/article/the-tfos-dry-eye-workshop-ii#:~:text=TFOS%20DEWS%20II%20defines%20dry,inflammation%20and%20damage%2C%20and%20neurosensory.
2. Efron, Nathan, et al. “Lid Wiper Epitheliopathy.” Progress in Retinal and Eye Research, Pergamon, 14 Apr. 2016, www.sciencedirect.com/science/article/abs/pii/S1350946216300131.
3. Varikooty, Jalaiah. “What Is Lid Wiper Epitheliopathy? .” Clspectrum.com, CL Spectrum , 1 Nov. 2015, www.clspectrum.com/issues/2015/november-2015/what-is-lid-wiper-epitheliopathy.
4. Feuerman, Jason, and Stephen Pflugfelder. “Tear Meniscus Dimensions and Location of Marx's Line in Meibomian Gland Dysfunction.” Investigative Ophthalmology & Visual Science, The Association for Research in Vision and Ophthalmology, 16 June 2013, iovs.arvojournals.org/article.aspx?articleid=2151744.
5. Yamaguchi, Masahiko, et al. “Marx Line: Fluorescein Staining Line on the Inner Lid as Indicator of Meibomian Gland Function.” American Journal of Ophthalmology, Elsevier, 28 Mar. 2006, www.sciencedirect.com/science/article/pii/S0002939405012079.
REFERENCES (CONTINUED)
6. Li, Wing, et al. “The Relationship of Lid Wiper Epitheliopathy to Ocular Surface Signs and Symptoms.” Investigative Ophthalmology and Vision Science, ARVO, Apr. 2018, iovs-arvojournals-org.proxy.lib.pacificu.edu:2443/article.aspx?articleid=2678073.
7. Kading, David L. Prevalence of Meibomian Gland Dysfunction Based on Meibomian Gland Expression, American Academy of Optometry, 2016, www.aaopt.org/detail/knowledge-base-article/prevalence-meibomian-gland-dysfunction-based-meibomian-gland-expression.
8. Morrow, Azinda. “What You Can Learn from Lids.” What You Can Learn From Lids, Review of Optometry, 15 Jan. 2019, www.reviewofoptometry.com/article/what-you-can-learn-from-lids.
9. Korb, Donald, and Caroline Blackie. “The Korb-Blackie Lid Light Test.” Investigative Ophthalmology & Visual Science, The Association for Research in Vision and Ophthalmology, 16 June 2013, iovs.arvojournals.org/article.aspx?articleid=2151763.
10. “TFOS DEWS II REPORT.” TFOS, 2017, www.tfosdewsreport.org/report-epidemiology_report/71_36/en/.
11. Park J;YooYS;Shin K;Han G;Arita R;Lim DH;ChungTY; “Effects of Lipiflow Treatment Prior to Cataract Surgery: A Prospective, Randomized, Controlled Study: Lipiflow Prior to Cataract Surgery.” American Journal of Ophthalmology, U.S. National Library of Medicine, 13 May 2021, pubmed.ncbi.nlm.nih.gov/33992615/.
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