4. 4
INTRODUCTIONINTRODUCTION
• Retinal vasculitis is a sight threatening
inflammatory eye disease affecting the retinal
vasculature.
• Presents as:
a. Periphlebitis: veins are affected
b. Periarteritis: arteries are affected or
c. Angiitis: as a combination of both
5. 5
CLINICAL CHARACTERISTICSCLINICAL CHARACTERISTICS
SYMPTOMS
• Asymptomatic if restricted to peripheral fundus
• Gradual, painless loss of vision (most common)
• Floaters (indicates significant migration of leukocytes to vitreous)
• Photopsia & reduced color vision (less common but
present in vasculitis surrounding macula)
• Central or Para central scotomata
6. 6
SIGNSSIGNS
• RAPD in M.S.
• Visual field defects
• Abnormal Amsler grid & color vision
• Elevated IOP in ocular toxoplasmosis
• A/C cells & Flare
• Neovasularization
• Vitrits
• Vitreous hemorrhages
7. 7
SIGNS OF PERIARTERITISSIGNS OF PERIARTERITIS
• Attenuation
• Sheathing (diagnostic)
• Cotton-wool spots
• Opaque superficial retina due to occlusion
10. 10
PRIMARY VASCULITISPRIMARY VASCULITIS
• Lymphopenia with normal helper T-cells to
suppressor T-cells ratio
• Increased conc. Of immune complexes
• Anticardiolipin antibodies
• Reduced antibody affinity to retinal-S antigen
• Increased expression of IL-2 surface markers
But their significance still remains to be seen
11. 11
INFECTIOUS VASCULITISINFECTIOUS VASCULITIS
• Vascular endothelium invaded by
microorganisms result in cell injury & death
• Immune complexes form with antigenic
components of microorganisms, activates
complement system, attract leukocytes & induce
inflammation
12. 12
IMMUNE VASCULITISIMMUNE VASCULITIS
• May be T cell mediated as in graft rejection,
giant cell arteritis & takayasu disease
• Ag-Ab & immune complex deposition is main
mechanism including eye
• Anti-endothelial cell antibody and anticardiolipin
antibodies are also associated with retinal
vasculitis
21. 21
EALES’ DISEASEEALES’ DISEASE
• An idiopathic obliterative vasculopathy affecting
peripheral retina of young males characterized
by recurrent vitreous hemorrhages
• 1st
described by Henry Eales in 1880 & 1882 in
men with Hx of recurrent headache, epistaxis,
dyspepsia & ch. Constipation
• Eales thought it to be due to vasomotor necrosis
but found it to be of venous inflammation
(periphlebitis)
22. 22
EPIDEMIOLOGYEPIDEMIOLOGY
• Most common in Indian sub. & middle east
• 1 in 200 or 250 ophthalmic pts in India
• Peak age = 20-35 yrs, although 13-63 yrs
reported too
• Males affected more
• Bilateral involvement in 50 – 90% pts
23. 23
ETIOLOGYETIOLOGY
A diagnosis of exclusionA diagnosis of exclusion
Idiopathic but associations….Idiopathic but associations….
• Tuberculosis
• Focal sepsis
• Thromboangitis
obliterans
• Brucellosis
• Syphilis
• Behcet’s disease
• Para nasal sinus
disease
• Infectious
mononucleosis
40. 40
LAB. TESTSLAB. TESTS
• CBC
• Blood glucose levels
• Sickle cell preparation & Hb electrophoresis
• ACE & Lysozyme levels
• ANA, RA factor, ESR
• Mantoux test
• PCR of M. tuberculosis in vitreous
41. 41
IMAGINGIMAGING
FFA
• Micro vascular abnormalities
• Neovasulariation & exudative sheathing will leak
• Helps to localize the area for laser application
44. 44
OTHER TESTSOTHER TESTS
• Increased conc. Of oxidation & per oxidation
products in vitreous *
• Decreased levels of antioxidant enzymes in
vitreous i.e. reduced glutathione, super oxide
dismutase, and glutathione peroxidase *
• Hearing & balance testing**
*Sulochana KN, Biswas J, Ramakrishnan S. Eales' disease: increased
oxidation and peroxidation products of membrane constituents
chiefly lipids and decreased antioxidant enzymes and reduced
glutathione in vitreous. Curr Eye Res. Sep 1999;19(3):254-9.
**Renie WA, Murphy RP, Anderson KC, et al. The evaluation of
patients with Eales' disease. Retina 3:243 248, 1983
45. 45
TREATMENTTREATMENT
MEDICAL
• Antioxidants
Vit. A, C & E
• Corticosteroids
systemic, subconjuntival, periocular
• Intravitreal Triamcinolone acetonide
for CME, Dose = 2-4mg
• Anti-VEGF (in studies showing good results)
46. 46
ANTI-TUBECULUOS TxANTI-TUBECULUOS Tx
• Presence of old tuberculosis lesion or positive
mantoux test may show some relation
• Reserved for those with acute phlebitis, massive
infiltration, nodule formation, obliteration of
vessels
• ATT regimen
Rifampicin 450 mg 1 x OD x 9 months
Isoniazid 300 mg 1 x OD x 9 months
47. 47
RETINAL ABLATIONRETINAL ABLATION
PHOTOCOAGULATION
Juntional area between perfused & non-perfused
area to be treated
• Argon green laser (514nm)
• Xenon arc photocoagulation
• Diode laser (810nm)
• Frequency doubled Nd:YAG laser (532nm)
ANTERIOR RETINAL
CRYOTHERAPY
• Convert hypoxic areas to anoxic arc, stops
proliferative Eales’ retinopathy
57. 57
TREATMENTTREATMENT
• Symptomatic
• No benefit from steroids despite
inflammatory process
• Pan retinal photocoagulation
• Pars plana vitrectomy plus endolaser
58. 58
COMPARISON WITH EALESCOMPARISON WITH EALES
EALES
• Perphlebitis
• Males more affected
• tuberculin
hypersensitivity
• temporal retina
• Steroids
recommended
IRVAN
•Periarteritis
•Female
•No relation
•Not specific
•No use
59. 59
INTERMEDIATE UVEITISINTERMEDIATE UVEITIS
• An insidious, chronic, relapsing disease with
vitreous major site of inflammation
• May be idiopathic or associated
• Pars planitis is idiopathic IU (85-90%) with
snowballs & snow banking
• Mild periphlebitis & nongranulomatous ‘spill over’
anterior uveitis
60. 60
NOMENCLATURENOMENCLATURE
Cyclitis Fuchs’ 1908
Peripheral uveitis Schepens 1950
Pars planitis Welch et al 1960
Chronic cyclitis Smith et al 1973
Basal uveoretinitis Bec et al 1977
Intermediate uveitis international uveitis 1987
study group
61. 61
EPIDEMIOLOGYEPIDEMIOLOGY
• PP more common in children
• Other IU 25-35 yrs
• IU is 15% of all uveitis cases & 20%
pediatric uveitis cases
• Bilateral 70-90%
• Clinical diagnosis
68. 68
PATHOGENESISPATHOGENESIS
• Yet to be ascertained
• Cell breakdown products in vitreous base may
act as antigen
• Relative ischemia leads to inflammation
• Ormerod et al* isolated Propionibacterium acnes
from vitroeus of pt with persistent PP
*ormerod LD, Puklin JE, Giles CL. Chronic propionibacterium acnes
endophthalmitis as a cause of intermediate uveitis, Ocular
immunology and inflammation 1997;4:67-68
74. 74
TREATMENTTREATMENT
• Treat the cause in IU
• In PP treat the inflammatory process
• Tx only indicated if
Vision 6/12 or less or
Evidence of CME
• Four step approach by Kaplan*
*Kaplan HJ. Intermediate uveitis a four step approach to
treatment. In Saari KM (Ed): Uveitis update Amsterdam: Excerpta
Medica 1984;169-72
75. 75
STEP 1STEP 1
• Posterior sub-tenon inj. Of depot steroids
methyl prednisolone 40 mg
triamcinolone acetonide 40 mg
• Can be repeated for 2-3 times with three weeks
interval
• Systemic steroid 60-80 mg/day alone or in
combo with periocular injections in severe cases
• I/vitreal triamcinolone
76. 76
STEP 2STEP 2
• If step 1 fails
• Cryopexy done to destroy hyperemic
vascular component
• Done by double freeze & thaw technique
• Laser photocoagulation for neovessels
77. 77
STEP 3STEP 3
• If step 2 fails & immunomodulatory agents not
indicated
• PPV with posterior hyaloid separation
and peripheral laser photocoagulation to
pars plana snow bank
78. 78
STEP 4STEP 4
• If all fails then systemic immunomodulatory
agents
Methotrexate
Cyclophosphamide
Cyclosporine
Azathioprine 50 mg x TDS….2 months
50 mg x BD……1 month
50 mg x OD……1 month
81. 81
FROSTED BRANCH ANGIITISFROSTED BRANCH ANGIITIS
• An acute panuveitis with severe vasculitis of
whole retina
• Veins more involved
• Also called diffuse retinal periphlebitis
• First described by ITO in Japanese literature in
1976, in 6 yrs old child with severe sheathing of
all retinal vessels appearing as frosted branches
of tree
83. 83
EPIDEMIOLOGYEPIDEMIOLOGY
• Rare, described in only 58 cases in literature
• Mostly in Japan…. Also north America, India &
turkey
• Typically bilateral but unilateral (28%)
• Males : females (52% : 48%)
• 6-16 yrs in Japan
• 23-29 yrs in other countries
86. 86
SIGNSSIGNS
• Acute visual loss
• Severe vascular sheathing
• retinal edema
• Vitritis and iridocyclitis
• Otherwise healthy patients
87. 87
• Papillitis, hard exudates, retinal
hemorrhages, venous occlusion are
uncommon
• Dye leakage from sheathed vessels in the
late phase of fluorescein angiogram and
no signs of stasis or occlusion.
89. 89
FFAFFA
• In early phase: normal venous flow & delayed
filling of arteries
• In late stages: leakage from vessels (veins more)
+ hyper fluorescence of optic disc are
characteristic
• Vessels narrowing but no occlusion
• Areas of non-perfusion
• A-V anastomosis
91. 91
VISUAL FIELDVISUAL FIELD
• Blind spot enlargement
• Central scotoma within 30 degrees due to
macular edema & exudates
ERG
• Reduction in amplitude of a- & b- waves
VECPs
• Pattern VECPs also reduced
93. 93
TREATMENTTREATMENT
• Treat the cause
• Systemic steroids
initial dose 80 to 100mg oral prednisone for
10 days
• Prognosis is usually very good with steroid Tx
visual acuity, field recovery in 2-3 months
97. 97
References for FBAReferences for FBA
• 1. Kleiner RC, Kaplan HJ, Shakin JL et al. Acute frosted retinal
periphlebitis. AJO 1988; 106: 27-34.
• 2. Sugin S, Henderly DE, Friedman SM et al. Unilateral frosted
branch angiitis. AJO 1991; 11: 682-85.
• 3. Hamed LM, Fang EN, Fanous MM, et al. Frosted branch angiitis:
the role of systemic corticosteroids. J Ped. Ophth. Strab. 1992; 29:
312-13.
• 4. Kleiner RC. Frosted branch angiitis: clinical syndrome or clinical
sign? Retina 1997; 17(5): 370-71.
• 5. Quillen DA, Stathopulos NA, Blankenship GW, et al. Lupus
associated frosted branch periphlebitis and exudative maculopathy.
Retina 1997; 17(5): 449-51.
98. 98
BIRDSHOTBIRDSHOT
RETINOCHOROIDOPATHYRETINOCHOROIDOPATHY
• Uncommon, idiopathic, chronic, recurrent,
bilateral posterior uveitis
• First described by Franceschetti and Bable in
1949
• In 1980, Ryan and Maumenee coined the term
birdshot*
• Gass called it vitiliginous choroiditis bcz of
similarity to cutaneous vitiligo
*Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J
Ophthalmol. Jan 1980;89(1):31-45
99. 99
• Deep, oval, creamy, indistinct spots
• Radiate from disc towards equator
• Moderate vitritis
100. 100
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
• Cause is unknown
• 80-95% are HLA-A29 positive
• LeHoang and coauthors reported all pts of BSRC
positive for HLA-A29 type 2 subtype*
• Nussenblatt and colleagues found relation of
BSRC with HLA-B12**
*LeHoang P, Ozdemir N, Benhamou A, et al. HLA-A29.2 subtype associated with
birdshot retinochoroidopathy. Am J Ophthalmol. Jan 15 1992;113(1):33-5.
**Nussenblatt RB, Mittal KK, Ryan S, et al. Birdshot retinochoroidopathy associated with
HLA-A29 antigen and immune responsiveness to retinal S-antigen. Am J
Ophthalmol. Aug 1982;94(2):147-58
104. 104
SIGNSSIGNS
• Decreased VA
• A/C cells
• KPs are rare
• Post. Synechiae
• Vitritis but no snowballs
• Retinal vasculitis involving large and small
vessels
• Optic disc edema & CME
105. 105
FUNDUSFUNDUS
• Small lesions with ¼- ½ DD, may be confluent
• Two types of lesions, present at posterior pole &
extend till equator
1. oval & not well demarcated. Pale
yellow or cream color spots easily
seen with indirect ophthalmoscopy
2. atrophic, sharply demarcated, round
“punched out” seen by both indirect
ophthalmoscopy & 78 or 98 D lens
109. 109
IMAGING STUDYIMAGING STUDY
FA
• Early hypo-fluorescence & late mild hyper-
fluorescence
ICG
• Well-defined hypo-fluorescent spots in early
phases, becomes hyper-fluorescent later
• Many more spots can be seen by ICG than FA
110. 110
FA of birdshot retinochoroidopathy
• Extensive late intraretinal and disc leakage
• Venous hyperfluorescence
111. 111
ELECROPHYSIOLOGYELECROPHYSIOLOGY
ERG
• Normal in early disease, but then decreased b-
wave amplitude & then oscillatory potential
• Delay in implicit time of 30 Hz flicker ERG is
most sensitive change
• ERG findings suggest intraretinal edema, so
correlate with retinal vasculopathy rather than
choroidal
112. 112
HISTOPATHOLOGYHISTOPATHOLOGY
Only 2 histopathological studies (on phthisical eyes)
• *Nussenblatt and coauthors described mild lymphocytic
response, retina involved with granulomatous
inflammation
• **Gaudio and coauthors described aggregation of the
lymphocytes with foci in choroid, optic nerve and retinal
vessels
*Nussenblatt RB, Mittal KK, Ryan S, et al. Birdshot retinochoroidopathy associated
with HLA-A29 antigen and immune responsiveness to retinal S-antigen. Am J
Ophthalmol. Aug 1982;94(2):147-58
**Gaudio PA, Kaye DB, Crawford JB. Histopathology of birdshot
retinochoroidopathy. Br J Ophthalmol. Dec 2002;86(12):1439-41
114. 114
STEROIDSSTEROIDS
• Conflicting results
• Some respond to local injectables, others
respond to systemic
• Some with low dose, other with high dose
• Topical steroids of no use
• Periocular steroids for CME
115. 115
CYCLOSPORINCYCLOSPORIN
• Very effective in BSRC with improved VA, dec.
vitritis, stable eye
• Vitale & Foster showed cyclosporin treatment in
low doses (2.5-5 mg/kg )*
• Maximum dose = 5 mg/kg with 4-6 weeks review
of renal function
• Used for a year at least, then tapered
*vitale AT, Rodriguez A, Foster CS. Low-dose cyclosporine therapy in the
treatment of birdshot
retinochoroidopathy. Ophthalmology. May 1994;101(5):822-31
116. 116
KETOCONAZOLEKETOCONAZOLE
• Can be used as an adjunct
• Ketoconazole delays metabolism of cyclosporin
• Silverstein and Wong demonstrate
cyclosporin 0.75mg/kg + ketoconazole 200mg/d
• However not very useful bcz of potential risks of
ketoconazole like hepatitis
117. 117
IMMUNOMODULATORSIMMUNOMODULATORS
• Kiss and colleagues *
mycophenolate mofetil, azathioprine,
methotrexate, and daclizumab but study was of
small size
• LeHoang and colleagues **
intravenous Immunoglobulin with stable vision of
33-36 eyes for 39 months
*Kiss S, Ahmed M, Letko E, et al. Long-term follow-up of patients with birdshot
retinochoroidopathy treated with corticosteroid-sparing systemic
immunomodulatory therapy
**LeHoang P, Cassoux N, George F, et al. Intravenous immunoglobulin (IVIg)
for the treatment of birdshot retinochoroidopathy. Ocul Immunol
Inflamm. Mar 2000;8(1):49-57
119. 119
COMPLICATIONSCOMPLICATIONS
• Chronic cystoid macular edema – 50%; the most
common cause of reduced central visual acuity
• Epiretinal membrane - 10%
• Macular pucker
• Choroidal neovascularization
• Peripapillary sub retinal neovascularization -
6%
120. 120
• Retinal neovascularization located on the optic
disc
• Peripheral retinal neovascularization with
capillary nonperfusion
• Optic nerve atrophy
• Other complications, such as cataract,
glaucoma, and rhegmatogenous retinal
detachment
122. 122
CAUSES OF R.V. IN PAKISTAN*CAUSES OF R.V. IN PAKISTAN*
• Departments of Ophthalmology, Jinnah
Postgraduate Medical Center, Karachi and
Chandka Medical college, Larkana
• April 1996 to December 2002
• 102 pts of R.V.
*Pak J Ophthalmol Apr 2004;20(2):53-6
123. 123
RESULTSRESULTS
• 50 pts(49%) diagnosed as Eales’ disease
• 28 pts(27.4%) had inactive tuberculosis
• 10 pts(9.8%) had raised serum ACE &
diagnosed as sarcoidosis
• 08 pts(7.8%) had active tuberculosis
• 04 pts(3.9%) had syphilis
• 02 pts(1.9%) had ocular toxoplasmosis
124. 124
TAKE HOME MESSAGETAKE HOME MESSAGE
• RV can be insidious, sight threatening
• Thorough examination
• Systemic associations
• Treat the cause
• Immunosuppressive in systemic diseases
126. 126
MCQsMCQs
1. Common cause of intermediate uveitis
a. multiple sclerosis
b. idiopathic
c. lyme disease
d. syphilis
Ans: b, (85-90%)
127. 127
2. Major cause of visual loss in pars planitis
a. band keratopahty
b. PSC
c. epiretinal membrane
d. CME
Ans: d
128. 128
3. The treatment of choice for BSRC is :
a. Topical steroids
b. Systemic steroids
c. Cyclosporin A
d. Oral tolerization of retinal S- antigen
Ans: c
129. 129
4. Which therapeutical intervention for pars
planitis is recommended as first choice?
a. Steroid drops
b. Systemic steroids
c. Non-steroidal anti-inflammatory drugs
d. Periocular steroid injections
Ans: d
130. 130
5. What are the most important differential
diagnoses to consider in case of frosted branch
angiitis?
a. Sarcoidosis and tuberculosis.
b. Multifocal choroiditis and panuveitis.
c. SLE and polyarteritis nodosa.
d. Wegeners’ granulomatosis.
e. All ocular and systemic diseases presenting
with retinal periphlebitis.
Ans: e
most often manifests as a gradual, painless loss of vision , Floaters , Photopsia is a less common presenting feature, as is reduced color perception, although the latter may indicate vasculitis surrounding the macula , central or Para central scotomata , corresponding to areas of retinal ischemia induced by vascular inflammation and subsequent occlusion , Vasculitis restricted to the peripheral fundus may be entirely asymptomatic ,
Elliot called it “Periphlebitis retinae” but later it was caller “Retinal vasculitis”
90% according to duke-elder
Eales disease. Fundus photo of the peripheral retina, revealing vascular tortuosity and peripheral retinal neovascularization.
Fluorescein angiogram of late leakage from peripheral retinal neovascularization in same patient