1. Uveitis: Systemic and Ocular Approaches to Management
Blair B Lonsberry, MS, OD, MEd., FAAO
Diplomate, American Board of Optometry
Clinic Director and Professor of Optometry
Pacific University College of Optometry

2. Case 1: Payne

3. Case
30 BF presents with eye pain in both eyes for the past several days
Severe pain (8/10)
Never had eye exam before
PMHx:
Has chronic bronchitis
Rash on legs
Has recently lost weight and has a fever
Taking aspirin for pain

4. Ocular Health Assessment
VA: 20/30 OD, OS
PERRL
FTFC
EOM”s: FROM with eye pain in all quadrants
SLE:
3+ injection,
3+ cells and trace flare,
deposits on endo (see photo)
IOP: 18, 18 mmHg
DFE:
see attached fundus image and fluorescein angiography.

5. Classification of Uveitis
4 main questions we need answered
Where is the inflammation located?
Is disease acute or chronic?
Granulomatous or non-granulomatous?
Unilateral or bilateral?

6. Classification of Uveitis
Secondary Questions:
Demographics of the patient
Has this happened before? If so did it respond to treatment?
Systemic questions:
Lung /breathing problems?
Rashes/skin problems?
Joint problems or low back pain?
Urination issues?
Digestive problems – diarrhea? Bloody stools? Cramps?
Have you been out of the country recently?
Have you been in a wooded area? Ticks?
Any other systemic/autoimmune diseases?
Use these secondary questions to further rule in/out similar causes of uveitis

7. Classification
Classification is the key to the proper diagnosis and management of the uveitic patient
Most common classifications
Anterior vs. Intermediate vs. Posterior vs. Panuveitis
Acute vs. Chronic/Recurrent
Granulomatous vs. Non-granulomatous
Infectious vs. Autoimmune
Classification makes the diagnosis much simpler.
If a person has uveitis – there can literally be dozens upon dozens of diseases that could be causing it
Whereas if we say that a 28 yoM has an acute, unilateral, non-granulomatous anterior uveitis that narrows down our options. We may not know what the exact diagnosis is but there are a lot of conditions that we are now more suspicious of and a lot that we are less concerned about

8. Anterior Uveitis Classification
Acute, unilateral (or bilateral), non-granulomatous anterior uveitis
Idiopathic, HLA-B27, Herpetic, Behcet’s
Chronic, bilateral (or unilateral), non-granulomatous anterior uveitis
JIA, Fuch’s Heterochromic, Idiopathic, Herpetic
Chronic, bilateral (or unilateral), granulomatous anterior uveitis
TB, Sarcoid, Syphilis, VKH

9. Ocular Manifestations-Uveitis
Signs/symptoms include:
pain,
photophobia,
blurred vision,
ciliary flush,
cells/flare,
rarely posterior involvement

10. Ciliary Flush, Cells, Flare

11. Treatment of Uveitis Treat the disease properly 2 main drugs/drops
Minimize complications of the disease itself
Minimize complications of the treatment
2 main drugs/drops
Cycloplegics
Topical Corticosteroids

12. Treatment Cycloplegia: used for reduction of pain,
break/prevent the formation of posterior synechiae
also functions in the reduction of inflammation
I have seen quite a number of corneal FB’s that have come into the ER here and have been in there for 2 or 3 days, even a week. A lot of the times they have a mild traumatic iritis going on, and by the time I remove the FB with the spud or the alger brush they might have a fairly decent epithelial defect and I might not want to put a steroid on it with that huge defect. If they are in a lot of pain, 1) I am going to put a bandage CL on them 2) I am going to cycloplege them, and I will probably prescribe Homatropine instead of just putting it in office. And often times that alone with take care of that mild traumatic iritis.

13. Cycloplegics cyclopentolate 1-2% tid for mild-to-moderate,
Common cycloplegic agents include:
cyclopentolate 1-2% tid for mild-to-moderate,
homatropine 5% or
scopolamine 0.25% or
atropine 1% bid-tid for moderate-to-severe inflammation
most common is the use of Homatropine 5% bid
be careful using atropine as there is potential for severe systemic side effects
Also makes the iris essentially immobile
can increase chances of peripheral anterior synechiae and peripheral posterior synechiae
In cases of chronic uveitis where there is a lot of flare and the AC has that sticky, fibrinous quality, tropicamide and cyclopentolate are the way to go since often times these patients are not in a lot of pain and we want to keep the pupil relatively mobil to prevent posterior synechiae

14. Uveitis: Treatment “Classical treatment”: Newer treatment option:
Pred forte: every 1-2 hours, ensure taper
Pred forte: prednisolone acetate formulation which allows penetration through cornea to anterior chamber
Newer treatment option:
Durezol

15. Treatment Steroids: necessary for the treatment of active inflammation
Most common is the use of prednisolone acetate 1% (e.g. Pred Forte 1%)
Phosphate form -> does not penetrate cornea well
Steroid medication that is felt to have less IOP response and report to not need as long of a taper is loteprednol etabonate (Lotemax)

16. Treatment options Durezol: Difluprednate Steroid emulsion BAK free
only difluorinated steroid
Steroid emulsion
BAK free
Increased “potency” so dosing needs to be less than “classical treatment” with Pred Forte
rough recommendation is 1/2 dosing of Pred Forte

17. Treatment
Topical administration is most common though periocular injections and systemic meds are useful for posterior uveitis and difficult cases
Dosing is dependent upon severity of the inflammation
typically you want to hit the uveitis hard and fast!
E.g 1 gtt q 2hrs until the inflammation is gone!
If you have a minimal anterior chamber reaction then steroid may not be necessary at all
Periocular route – intermediate uveitis, posterior uveitis, CME, severe anterior uveitis unresponsive to topical meds
given every month until the desired effect is achieved
Systemic meds – severe posterior uveitis/panuveitis or anterior uveitis unresponsive to topical/periocular therapy

18. Treatment NOTE: it is crucial to taper your steroid treatment!
You will have a rebound inflammation if you simply remove your patient from their steroids…
The taper will be dependent upon how long you have had them on the steroid to get rid of the inflammation!
Typically, a slow taper is better in order to prevent rebound inflammation
If the patient has been on the steroid for less than a week a faster taper can be considered.
And if you get rebound inflammation now you are setting yourself up for second guessing yourself. Did I miss something more serious, is the uveitis back and its now a recurrent uveitis for which I might send the patient for expensive lab-work?
We taper based on the patients symptoms, some patients you may have to taper for months or even years.
Every time the uvea is inflamed and opened up it is more susceptible to recurrent inflammation. So if a patient has had a recurrent inflammation 4-5 times you are going to have to taper them much more slowly.
To prevent a low-grade smoldering iritis, you must treat beyond the cell and flare. In other words, if you taper corticosteroids too quickly in any case of iritis, especially a case associated with a systemic condition, such as Crohn's disease, sarcoidosis or ankylosing spondylitis, low-grade anterior chamber inflammation could linger dormant or even "reignite." By maintaining prolonged steroid dosing, even as conservatively as q.d. for one week after cell and flare are no longer evident in the anterior chamber, you can help prevent a rebound iritis.

19. Treatment
NSAIDs:
do not play an important role in the treatment of an acute uveitis
may be used in the treatment of a chronic uveitis such as in a JRA patient who is using NSAIDs for the treatment of systemic pain.
May be used as an adjunct to allow lower doses of corticosteroid

20. Treatment: Additional Therapies
Immunosuppressive agents (cytotoxic)
reserved for sight-threatening uveitis that have not responded to conventional treatment
e.g. cyclophosphamide
Antimetabolites (e.g. methotrexate) have been found useful in JRA related iridocyclitis and scleromalacia
Cyclosporin has a very specific effect on the immune system and has been found useful in posterior and intermediate uveitis

21. Follow-up
Every 1-7 days in acute phase depending upon severity and every 1-6 months when stable.
On each f/u visit the AC reaction and IOP should be evaluated
DFE should be performed for flare-ups, when VA affected, or every 3-6 months.

22. Follow Up
If AC reaction improving, then steroid drops can be slowly tapered.
cycloplegia can also be tapered as the AC reaction improves.
slow taper recommended for chronic granulomatous uveitis.

23. Rules For Managing Uveitis
Remember the classifications.
Determine if there is corneal involvement & check IOP.
Determine the severity.
Is this a chronic problem?
Treat strongly.
Remember the classifications. Remember what are the most likely causes. Remember which systemic ?’s to ask (joint/back aches, rashes, urination problems, gut problems, breathing problems).
Rule out a keratouveitis. Look for infiltrates. Are they a CL wearer? Apply NaFl & rose bengal to look for other corneal findings (epithelial defects, dendrites). Have to rule out a bacterial keratitis/ulcer, fungal keratitis, herpetic keratouveitis. Because the typically treatment for an idiopathic or even systemically caused uveitis is steroids & cycloplegic. Steroids would make all 3 causes above much worse.**
Determine the severity. Is it unilateral or bilateral? Is this a recurrent condition? Are KP’s present? Are synechiae present? Is a severe anterior chamber reaction present? If 3 or more of these major findings are present, then this is likely a systemic/severe presentation and a medical workup is probably appropriate.
Chronic problems. Much more likely to develop IOP spike/glaucoma, cataracts, CME, etc.
To help alleviate #4, Rx strong steroids!!! For Pred Forte or Lotemax, dosing should be q2h or q1h only. (This even applies to low-grade uveitis cases, because you can taper the dose once improvement is noted.) The use of a generic steroid, however, is cautioned against, unless the patient is well educated about shaking the bottle vigorously.

24. Case 23 WM POHx: PMHx: Meds: Eye pain OD Severe, started 2 days ago
Photophobia and redness
POHx:
Had similar problem and was given drops and felt better
PMHx:
Told to get back into shape and to reduce stress
Meds:
Ibuprofen for lower back pain

25. Assessment VA: 20/20-, 20/20+ Entrance skills unremarkable SLE:
OD:
2+ injection,
2+ cell,
Mild flare,
Fine deposits
IOP: 18, 14 mm HG
DFE: unremarkable

26. HLA-B27 Conditions

27. Ankylosing Spondylitis
Ankylosing spondylitis is a type of arthritis that affects the spine:
symptoms include pain and stiffness from the neck down to the lower back.
The vertebrae may grow or fuse together, resulting in a rigid spine.
these changes may be mild or severe, and may lead to a stooped-over posture.

28. Ankylosing Spondylitis
Ankylosing spondylitis affects about 0.1% to 0.5% of the adult population.
Although it can occur at any age, spondylitis most often affects men in their 20s and 30s.
It is less common and generally milder in women and most common in Native Americans.
Early diagnosis and treatment helps control pain and stiffness and may reduce or prevent significant deformity.

29. Ankylosing Spondylitis
Physical Exam:
The overall points taken into account when making an AS diagnosis are:
Onset is usually under 35 years of age.
Pain persists for more than 3 months (i.e. it is chronic).
The back pain and stiffness worsen with immobility, especially at night and early morning.
The back pain and stiffness tend to ease with physical activity and exercise.
Positive response to NSAIDs (nonsteroidal anti-inflammatory drugs).

30. Ankylosing Spondylitis
X-rays:
The hallmark of AS is involvement of the sacroiliac (SI) joint
show erosion typical of sacroiliitis (inflammation of the sacroiliac joints).
can take 7 to 10 years of disease progression for the changes in the SI joints to be serious enough to show up in conventional x-rays.
Pre-Surgery
Post-Surgery

31. Ankylosing Spondylitis
HLA-B27 testing:
Generally speaking, no more than 2% of people born with this gene will eventually get spondylitis
it is important to note that the HLA-B27 test is not a diagnostic test for AS
the association between AS and HLA-B27 varies in different ethnic and racial groups.
over 95% of people in the caucasion population who have AS test HLA-B27 positive.
only 50% of African American patients with AS possess HLA-B27
close to 80% among AS patients from Mediterranean countries.

32. Ankylosing Spondylitis
Treatment:
A common treatment regimen involves:
Medication (NSAIDs, Methotrexate, Anti-TNF),
exercise and possibly physical therapy,
good posture practices,
applying heat/cold to help relax muscles and reduce joint pain.
In severe cases surgery may also be an option.

33. Psoriatic Arthritis
Psoriasis is a scaly rash that occurs most frequently on the elbows, knees and scalp, but can cover much of the body.
It is a chronic, inflammatory disease of the skin, scalp, nails and joints.
A normal skin cell matures and falls off the body's surface in 28 to 30 days, but a psoriatic skin cell takes only three to four days to mature and gathers at the surface, thus forming lesions.

34. Psoriatic Arthritis
In 5-10% of those with psoriasis, arthritis also appears.
In most cases the psoriasis will precede the arthritis, sometimes by many years.
When arthritis symptoms occur with psoriasis, it is called psoriatic arthritis (PsA).
the joints at the end of the fingers are most commonly affected causing inflammation and pain, but other joints like the wrists, knees and ankles can also become involved.
usually accompanied by symptoms of the fingernails and toes, ranging from small pits in the nails to nearly complete destruction and crumbling as seen in reactive arthritis or fungal infections.

35. Psoriatic Arthritis
About 20% of people who develop PsA will eventually have spinal involvement, which is called psoriatic spondylitis.
The inflammation in the spine can lead to complete fusion - as in ankylosing spondylitis - or skip areas where, for example, only the lower back and neck are involved.
Those with spinal involvement are most likely to test positive for the HLA-B27 genetic marker.
Up to 40% of people with PsA have a close relative with the disease, and if an identical twin has it, there is a 75% chance that the other twin will have PsA as well.

36. Psoriatic Arthritis
Treatment for psoriasis remains suppressive, rather than curative.
Treatment of articular manifestations generally begins with non-steroidal anti-inflammatory agents (NSAIDs).
In patients with aggressive and potentially destructive disease, disease-modifying anti-rheumatic drugs (DMARDs) should be added early on in the course (Methotrexate, TNF-blockers, anti-malarials).

37. Reactive Arthritis
Reactive Arthritis (also known as Reiter's Syndrome) is a form of arthritis that can cause inflammation and pain in the:
joints, the skin, the eyes, the bladder, the genitals and the mucus membranes.
Reactive arthritis is thought to occur as a "reaction" to an infection that started elsewhere in the body, generally in the genitourinary or gastrointestinal tract.

38. Reactive Arthritis
Reactive arthritis occurs after exposure / infection caused by certain types of bacteria. These include:
Chlamydia, a bacterium contracted during sexually activity, which causes either burning urination or watery discharge from the penis or vagina.
Bacteria such as Salmonella, Shigella, Yersinia or Campylobacter, which cause dysentery (diarrhea, abdominal pain, vomiting, fever). Exposure to these bacteria occurs after eating spoiled or contaminated food.
Not everyone exposed to these bacteria will contract ReA.
Those who go on to develop ReA tend to test positive for the HLA-B27 genetic marker, although other genetic factors may be involved.
Thus, it is an interaction between an individual's genetic make-up and the initial infection that causes Reactive Arthritis.

39. Reactive Arthritis ReA usually develops 2-4 weeks after the infection.
A tendency exists for more severe and long-term disease in patients who do test positive for HLA-B27 as well as those who have a family history of the disease.
Reactive Arthritis typically follows a limited course, where symptoms subsiding in 3-12 months.
However, the condition has a tendency to recur.
About 15-20% of people with ReA develop a chronic, and sometimes severe, arthritis or spondylitis.

40. Reactive Arthritis
Treatment of reactive arthritis is based on where it has become manifest in the body.
For joint inflammation, patients are generally initially treated with NSAIDs.
prednisone is used in the short-term treatment of inflammation in reactive arthritis
for the aggressive inflammation of chronic joint inflammation medications that suppress the immune system such as methotrexate

41. ReA Conjunctivitis
Eye involvement occurs in about 50% of men with urogenital reactive arthritis and about 75% of men with enteric reactive arthritis.
Conjunctivitis and uveitis can include redness of the eyes, eye pain and irritation, or blurred vision.
Eye involvement typically occurs early in the course of reactive arthritis, and symptoms may come and go
Treatment includes NSAIDs and/or steroids

42. Enteropathic Arthritis
Enteropathic arthritis is a form of chronic, inflammatory arthritis associated with the occurrence of an inflammatory bowel disease (IBD):
the two best-known types of which are ulcerative colitis and Crohn's disease.
About one in five people with Crohn's or ulcerative colitis will develop enteropathic arthritis.
The most common areas affected by enteropathic arthritis are inflammation of the peripheral (limb) joints, as well as the abdominal pain and possibly bloody diarrhea associated with the IBD component of the disease.
In some cases, the entire spine can become involved as well.

43. Enteropathic Arthritis
The course and severity of enteropathic arthritis varies from person to person.
The disease "flares" - the times when the disease is most active and inflammation is occurring - tend to be self-limiting, often subsiding after 6 weeks, but reoccurrences are common.
In some cases the arthritis may become chronic and destructive.

44. Treatment
A common treatment regimen for all the spondyloarthropathies (ankylosing spondylitis, reactive arthritis, psoriatic arthritis, enteropathic arthritis, and undifferentiated spondyloarthropathy) involves medication, exercise and possibly physical therapy, good posture practices, and other treatment options such as applying heat/cold to help relax muscles and reduce joint pain.
In severe cases of ankylosing spondylitis, surgery may also be an option.

45. Treatment
Medication
NSAIDs (nonsteroidal anti-inflammatory drugs) are still the cornerstone of treatment and the first stage of medication in treating the pain and stiffness associated with spondylitis.
However, NSAIDs can cause significant side effects, in particular, damage to the gastrointestinal tract.
When NSAIDs are not enough, the next stage of medications, (also known as second line medications), are sometimes called disease modifying anti-rheumatic drugs (DMARDS).
This group of medications include: Sulfasalazine, Methotrexate and Corticosteroids.

46. Treatment
Medication
The most recent and most promising medications for treating ankylosing spondylitis are the biologics, or TNF Blockers. These drugs have been shown to be highly effective in treating not only the arthritis of the joints, but also the spinal arthritis. Included in this group are Enbrel, Remicade, Humira and Simponi

47. References Spondylitis Association of America

48. Juvenile Idiopathic Arthritis

49. Juvenile Rheumatoid Idiopathic Arthritis (JRA/JIA)
“Rheumatoid like” disease with onset before age 17
Group of arthritides responsible for significant functional loss in children
Most common chronic disease with genetic predisposition in children.
2:1 female:male, with peak incidence b/w 2-4 and then 10-12

50. Natural History Pathogenesis unknown
Immune-mediated activity directed towards Type II collagen
RF mediated responses rarely found
1o involves weight bearing joints of lower extremities (knees/ankles) as well as joints of elbows/hands
Little associated pain/tenderness observed

51. Diagnosis
Synovitis that persists for at least 6 weeks is the essential criterion for diagnosis.
Hematologic and radiographic studies are beneficial in diagnosis and classification.
Fewer than 20% of patients have positive RF
Radiographic evaluation of inflamed joints reveal soft tissue swelling and peri-articular osteoporosis with possible new bone formation.
Loss of the cartilaginous space with erosions occur after long duration.

52. Treatment and Management-Systemic
Primary goal is to control pathologic changes in articular tissues
Typically runs self limiting course
medical therapy needed only when persistent arthritis warrants Tx.
ASA plays significant role in Tx in conjunction with exercise.
NSAIDs have gained popularity and a few are approved for JIA.
Dose dependent on body mass (e.g. indomethacin 1-3mg/kg/day TID)

53. Treatment and Management-Systemic
Antimalarial not used as frequently as in RA
efficacy is good but toxicity a concern
when used they are limited to a 2 year course at 5-7 mg/kg/day.
Use of gold salts common when arthritis not responding to ASA or NSAIDs.
Immunosuppressive reserved for life threatening cases or cases unresponsive to other conservative therapies.
Proper DX and TX results in recovery in about 85% cases

54. Ocular Manifestations
Classic triad of iridocyclitis, cataract and band keratopathy
Overall incidence of iridocyclitis is apprx 20%.
Cataract, glaucoma, and band keratopathy are seen in 50% of patients who develop persistent iridocyclitis.

55. Ciliary Flush, Cells, Flare

56. Ocular Manifestations
Severe vision loss results primarily from cataract formation and less frequently from band keratopathy.
Insidious onset of ocular involvement, with the iridocyclitis commonly following the arthritis symptoms (though occasionally preceding)
Patients are often asymptomatic and therefore require ocular evaluation for detection

57. Ocular Manifestations
Evidence of chronic iridocyclitis may be presenting sign leading to Dx of JIA
Posterior segment involvement is not commonly seen
Band keratopathy in children <16 is pathognomonic for JIA
results from aggressive/chronic ocular inflammation (not abnormal calcium metabolism).
JIA patients do not present with the dry eye and K sicca manifestations that are so prevalent in RA.

58. Treatment and Management-Ocular
Systemic medical therapy has minimal effect on ocular inflammation
Topical steroids and short acting cycloplegics remain primary treatment
Decreased VA 2o to cataract requiring extraction
Band keratopathy develops in eyes with chronic iridocyclitis and require treatment with chelating agents
Patients who develop glaucoma need to be treated aggressively