9/30/2019 1 Zanna Kruoch, OD, FAAO, ABO Diplomate, FSLS Clinical Assistant Professor University of Houston, College of Optometry › I have received honoraria from: – Essilor Custom Contact Lens Specialist › Clinical Assistant Professor – University of Houston, College of Optometry › Opinions from this lecture are my own › Identify key elements in an examination to aid in the diagnosis of uveitis. › When to utilize further history and/or laboratory testing to aid in the diagnosis of uveitis. › Be able to build a list of systemic differentials associated with uveitis. The Fundamentals of Building the Ocular Differentials CC: “red, painful eye" › CC: red, painful eye › HPI: – Right eye – Onset 4 days ago – Gradually getting worse – Constant – 1 st episode started 2 years ago. Occurs every 3-4 months. Only right eye. – Associated symptoms: photophobia, pain on the right side of the head – No discharge – Mild head relief with Tylenol BID po
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Zanna Kruoch, OD, FAAO, ABO Diplomate, FSLSClinical Assistant ProfessorUniversity of Houston, College of Optometry
› I have received honoraria from:– Essilor Custom Contact Lens Specialist
› Clinical Assistant Professor – University of Houston, College of Optometry
› Opinions from this lecture are my own
› Identify key elements in an examination to aid in the diagnosis of uveitis.
› When to utilize further history and/or laboratory testing to aid in the diagnosis of uveitis.
› Be able to build a list of systemic differentials associated with uveitis.
The Fundamentals of Building the Ocular Differentials
CC: “red, painful eye"
› CC: red, painful eye
› HPI: – Right eye– Onset 4 days ago– Gradually getting worse– Constant– 1st episode started 2 years ago. Occurs every 3-4 months. Only
right eye.– Associated symptoms: photophobia, pain on the right side of the
head– No discharge– Mild head relief with Tylenol BID po
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› POH:– Unremarkable
› PMH:– Hypothyroidism, primary
› Systemic Medications:– Levothyroxine
› ALL:– Penicillin
› Intraocular Pressures – OD 38 mmHg– OS 14 mmHg– Time: 8:39 am
› VA (sc)– OD 20/20– OS 20/25, PH 20/20
› EOMs– Unrestricted OD, OS
› CF– FTFC OD, OS
› PERRL (-) APD– Marked photophobia
Determining the ocular differentials
DIFFERENTIALS?
Infectious Conjunctivitis / Keratitis
Staph. Hypersensitivity / Sterile Ulcer
Dry Eyes
Corneal Abrasion
Recurrent Corneal Erosions
Scleritis
Uveitis
DRAWBOARD• Age/Race/Gender:
• 41 yro:• Collagen-vascular auto-
immune?• MS?
• Hispanic:• Secondary inflammation from
DM?• Female
• Adnexa / External:• No lid lesions evident• No lid edema• Hyperemia, no evident discharge• No heavy flaking or madarosis
› Uveitis accounts for 5-10% of visual impairment worldwide
› Literature review by Tsirouki over 40 years through 2015:– Incidence: 17 to 52 per 100,000 of population per year– Prevalence: 38 to 714 cases per 100,000 of population per
year– Accounts for up to 25% of legal blindness
› Anatomical location: Where is located?
› Clinical Course: Acute or chronic?
› Etiology: Infectious or non-infectious?
› Histopathology: Granulomatous or nongranulomatous?
› Laterality: Unilateral or bilateral?
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› Anterior: anterior chamber
› Intermediate: vitreous
› Posterior: retina and/or choroid
› Pan: all of the above
› Acute: episode of sudden onset and limited duration
› Chronic: Repeated episodes separated by periods of inactivity without treatment lasting > 3 months
› Recurrent: Persistent uveitis with relapse in < 3 months after discontinuing treatment
› Etiology: – What is the demographics of the patient? – Infectious or non-infectious?
› Histopathology: – Granulomatous or nongranulomatous?
› Uveitis accounts for 5-10% of visual impairment worldwide
› Literature review by Tsirouki over 40 years through 2015:– Incidence: 17 to 52 per 100,000 of population per year– Prevalence: 38 to 714 cases per 100,000 of population per
› WBCs that collects on the back of the endothelium– Fresh KPs – round, white, regular in shape– Old KPs- irregular in shape, pigmented
› Sign of chronic inflammation– Size matters!
› Types:– Fine KPs – typically non-granulomatous– Mutton fat KPs – typically granulomatous– Stellate KPs – part of Fuch’s Heterochromic
Iridocyclitis
› Anterior chamber flare, resulting from extra protein in the aqueous, is usually present.
– 0 = None– 1+ = Faint– 2+ = Moderate (iris and lens detail clear)– 3+ = Marked (iris and lens detail hazy)– 4+ = Intense (fibrin or plastic aqueous)
› Cells, the hallmark of iritis, are present in the aqueous. They should be graded by severity under high-magnification slit lamp examination in a 1 X 3-mm field of light
› Highly variable based on geography– Behcets: Japan, Taiwan, Korea, Italy, Portugal– VKH: common in Asia; also reported in South America– Sarcoidosis: Western world; also reported in Japan– Onchocerciasis: Sierra Leone
› High reports of idiopathic etiology in USA, Europe, Australia
› Accounts for 30-50% of uveitis› Manifests as posterior uveitis or panuveitis› Common etiologies:
Tests Conditions/CommentsCBC with diff Underlying systemic condition, WBC Liver function tests Sarcoidosis, hepatitisAngiotension-converting enzyme (ACE)
Sarcoidosis
ANA SLE, other rheumatic diseaseANCA Wegener’s granulomatosis, polyarteritis nodosaAntiviral Ab Viral infectionESR Underlying systemic disease; to check for presence of
inflammationHLA typing Specific HLA typesRF / Anti-CCP Rheumatoid arthritisRPR/FTA-ABS SyphilisCultures Bacterial, fungal, mycobacterial, viral diseasesLumbar puncture Malignancy, Syphilis, VKH, infection and more
Tests Conditions/CommentsMRI of head Malignancy, multiple sclerosis
and 1 gtt Azopt OS. Start Durezol QID OS, HomatropineBID, and Azopt BID OS. Return 3 days for follow-up and fundus evaluation. Uveitis survey given to patient to complete.
› Series of questions to help identify systemic cause of uveitis
› When to administer survey:– Nonresponsive to treatment– Granulomatous anterior uveitis– Recurrence of uveitis– Posterior uveitis
› Pros:– Detailed and easy to understand for patients– Inclusive– Useful in deciding what bloodwork to order
› Cost effective
› Cons:– Symptoms that may be late in the course of the disease; not
very useful– May need to repeat
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› Several online available› Uveitis.org offers an example:
› Subtypes:– HSV-1: infection in or around mouth– HSV-2: infection of genital or anal area
› HSV-1:– More likely to cause ocular complications than HSV-2– Highly contagious– Commonly acquired during childhood and remains latent and
asymptomatic– Symptoms:
› Mildly painful mouth sores› In immunocompromised patients, severe symptoms can occur with
frequent recurrence
› Most common manifestation: HSV Keratitis– Granulomatous inflammation from Descemets to Bowmans in
stromal disease– T-cell mediated immune response with HSV antigens located in
deep stroma and endothelium– Can affect all layers of the cornea
› HSV Epithelial Keratitis is the most common herpetic infection› HSV Stromal Keratitis is the most common recurrent herpetic infection
› HSV-associated Uveitis:– Typically unilateral– Associated with acute ocular hypertension– Can be nongranulomatous or granulomatous inflammation– Residual damage can lead to iris atrophy
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› Chronic granulomatous inflammation that can affect several organs
› Gold standard of diagnosis is the presence of non-caseating granulomata on tissue biopsy– Ancillary testing can be obtained if biopsy is not possible
› Ocular involvement can occur before systemic disease in up to 30% of cases
› Bimodal age distribution of ocular sarcoidosis– 20 to 30 yro– 50 to 60 yro
› African Americans are more likely to develop ocular involvement than Caucasians
› Females more likely than males to develop ocular involvement
› Most common:– Uveitis– Dry Eye– Conjunctival Nodules
› Less common:– Multifocal choroiditis– Retinal vasculitis:
› Ocular involvement:– Decrease vision or visual field defect– Visual hallucinations– Papilledema– EOM defects– Pupillary defects
› Other neurological involvement:– Cranial neuropathy: optic and facial most commonly affected– Encephalopathy– Vasculopathy– Peripheral neuropathy– Meningitis– Hydrocephalus
› Ocular Sarcoidosis can affect any structure of the eye and its adnexa.
› Uveitis is one of the most common findings.
› Race, age, chronic history
› HSV typically presents with corneal inflammation
› Uveitis can occur in HSV but not as likely
› Lack of iris atrophy
Tests Conditions/CommentsCBC with diff Underlying systemic condition
Angiotension-converting enzyme (ACE) Sarcoidosis
ANA SLE, other rheumatic diseaseANCA Wegener’s granulomatosis, polyarteritis nodosaAntiviral Ab Viral infectionESR Underlying systemic disease; to check for presence of
inflammationHLA typing Specific HLA typesRF Rheumatoid arthritisVDRL/FTA-ABS SyphilisChest X-Ray Tuberculosis, SarcoidosisPurified protein derivative (PPD) Tuberculosis
Sacroiliac x-ray Ankylosing spondylitis
Lysozome Sarcoidosis
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› Common:– Chest X-Ray for presence bilateral hilar lymphadenopathy– Elevated serum levels of ACE and/or lysozyme
› Other:– Chest CT if clear CXR– Abnormal liver enzymes– Negative tuberculin in BCG vaccinated patients
› So does this mean this is NOT Sarcoidosis?
› Up to 10% can present with clear CXRs
› Further testing needed
Requested Results
CBC with diff Normal including liver enzymes
ESR Not performed
ACE/Lysozyme Not performed
CXR Clear
PPD Not performed
FTA-ABS/RPR Not performed
› OS:– Significant drop in VA to CF– Development of iris bombe, glaucoma, cataract
› Never was able to obtain clear view of retina– Referred to county hospital for CE, retina evaluation
› BCVA 20/250 s/p CE
› OD:– Developed granulomatous uveitis– Followed similar course as OS– Continued care with OMD at county hospital
› High suspicion of underlying condition of Sarcoidosis– Pending results
CC: Flashes & Floaters
› CC: flashes and floaters
› HPI: – OS > OD– Persistent flashes OS started 2 months ago, OD has occurred
“every now and then”– Associated symptoms:
› Constant “cloudy vision OS” which started before flashes› Experiencing vertigo with flashes and cloudy vision
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› POH:– Retinal tear s/p laser OS – 2 years prior
› PMH:– Adult Rheumatoid Arthritis– HIV: per pt “well controlled” although unknown CD4 and viral load
› Prior symptoms:– Night sweats– Fatigue– Poor appetite– Tingling/numbness of ears– Hearing/ringing of ears– Painfully cold fingers– Sore in the
throat/sneezing/sinus problems
DIFFERENTIALS:TuberculosisSarcoidosis
SyphilisHSV/VZV/CMV/EBV
VKHAIDS/HIV
Rheumatoid Arthritis
› Symptoms:– Stiff joints– Stiff lower back– Back pain while sleeping
› Social Hx:– Owned dogs– Bisexual/homosexual relations
DIFFERENTIALS:TuberculosisSarcoidosis
SyphilisHSV/VZV/CMV/EBV
VKHAIDS/HIV
Rheumatoid ArthritisAnkylosing Spondylitis
Toxocariasis
DIFFERENTIALS:TuberculosisSarcoidosis
SyphilisHSV/VZV/CMV/EBV
VKHAIDS/HIV
Rheumatoid ArthritisAnkylosing Spondylitis
Toxocariasis
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› Inflammatory polyarthritis characterized by inflammation of the joint, leading to synovial joint destruction– Extremities– Cervical spine
› Females > Males
› Can start at any age but most common ages of 40-60
› 25% of RA patients will have ocular involvement
› Greater tendency to affect anterior vs. posterior segment– Most common:
› Dry eyes› Episcleritis / Scleritis:
– May extend to uvea causing uveitis› Peripheral ulcerative keratitis
– Less common:› Choroiditis› Retinal vasculitis (sub-type of uveitis)› Macular edema› Retinal detachments
› Scleritis: – Uncommon inflammation of sclera usually resulting in extreme pain– Scleritis prevalence of 4-10% in RA patients– RA-related scleritis makes up 1/3 of all scleritis cases– Anterior scleritis is much more common than posterior (90% vs 10%)
› Classified base on:– Distribution:
› Diffuse affecting one or more quadrants› Nodular with tenderness and scleral thickening
– Destruction: › Necrotizing › Non-necrotizing
› Uveitis:– Not typically associated with adult RA– Present concurrently with scleritis
› Retrovirus largely affecting helper CD4+ T cells resulting in severe immunosuppression
› Initially homosexual/bisexual activity accounted for most transmission until early 1990s; now heterosexual activity is the major route of transmission– IV drug abuse– Perinatal transmission– Needle stick injury
› Can affect almost every tissue of the eye– Most common:
› CMV Retinitis most frequent ocular infection in HIV – If uveitis present typically mild non-granulomatous uveitis – Clinical presentation:
› Slowly progression of retinal whitening spreading along the vasculature with hemorrhages
› Necrosis leads to thin atrophic retina leading to higher risk of RDs› Optic nerve may be involved› Low grade vitritis
› Immune Recovery Uveitis– Uveitis that occurs in pts with CMV retinitis on HAART therapy– Thought of as a boost in the immune system from HAART
therapy – Typically presents with vitritis– Directly related to the severity of the CMV retinitis
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› Granulomatous anterior uveitis responded well treatment with taper over first 8 weeks– BCVA OS 20/20 by end of week treatment– Clear of anterior chamber reaction and resolution of KPs
› The following labs were requested:– CBC with diff– RF / ANA– CD4+ / viral load – VDRL/RPR– HLA-B27
CD4+ 429 cells/uL Questionable HIV/AIDSViral load 12260 copies/mL Uncontrolled HIV/AIDSCXR Clear Unlikely TB or SarcoidosisHLA-B27 Not performed n/aVDRL/RPR Not performed n/aQuantiferon-TB Gold Negative Unlikely TBESR Elevated Presence of inflammation
ANA Screening Negative Unlikely SLE, Scleroderma, other mix connective tissue
› 6 week f/u:– Results of lab– Pt admits being off HIV medications for several months but
by 6 week f/u with us, back on HIV meds x 3 weeks
› Over course of 5 months:– Pt treated for rebounding anterior uveitis– Responded well to treatment but tendency to rebound
during taper
› CC: – Floaters OS– Physician directed f/u for recurrent uveitis OU
› HPI: – Floaters:
› Sudden increase for several hours with one large floater remaining, some photopsia, noticed 1 week ago. Mild “fog” in superior vision.
– Recurrent uveitis OU:› Taper OD Durezol 1 gtt every other day; OS Durezol QID x 2 weeks.
› Auto-immune disease characterized by bilateral uveitis– HLA-DR4– Viral triggers
› Higher incidence in Asians, native Americans, Hispanics, Middle Easterners
› Associated with meningeal, auditory, integumentary manifestations– Neurological and auditory occurs prior to uveitis– Integumentary tends to occur after uveitis
› Prodromal:– 1-2 weeks with flu-like symptoms
› Acute:– Acute bilateral posterior uveitis– Non-granulomatous nature first two weeks– Dec VA
› Chronic: – Signs of depigmentation of uveal tissue
› “Sunset glow fundus” depigmentation of the choroid is the most common sign› Nummular chorioretinal scarring
– Signs of depigmentation of integumentary:› Poliosis, alopecia, vitiligo
› Chronic recurrent:– Mild panuveitis with recurrent episodes of anterior uveitis– Recurrence of uveitis changes from nongranulomatous to granulomatous
› Herpetic etiology– VZV most common– HSV second most common
› Generally in immune-competent individuals
› Clinical Presentation:– One or more areas of retinal necrosis
with distinct borders in peripheral retina
› Circumferential spread– Inflammatory reaction of anterior or
› Almost 50% of nongranulomatous, anterior uveitis is positive to HLA-B27
› What does this mean?– Resistance to traditional therapy– Recurrence particularly in surgically induced inflammation– Systemic signs/symptoms
› Chronic condition that affects several organs, generally the sacroiliac joints
› Young white males– 2nd decade of life
› Symptoms:– Lower back pain– Symptoms worse in the morning or without activity– Improvement with exercise
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› Greater anterior segment involvement vs. posterior segment
› Presents most commonly as uveitis:– Anterior, non-granulomatous– Greater tendency to have more inflammation with ocular
surgeries– Greater severity relative to idiopathic uveitis
› Treatment:– More resistant to traditional therapies– Require more aggressive steroids – Consult with PCP for medical management
› Understanding the key elements to make a diagnosis of uveitis– CC & History– Clinical signs
› Hallmark› Other subtle signs
› Utilize additional tests to aid in the systemic cause of uveitis– Survey– Laboratory testing
› Create the systemic differentials– Utilize the history and clinical signs– Pull from the uveitis survey– Use laboratory testing (and repeat testing) to confirm your
suspicion.
› Be flexible!– The course of the condition may change.– Your differentials may change.
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