Retinal Vasculitis
`
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`Original article
`contributed by:
`
`All contributors:
`
`Aniruddha Agarwal, MD
`
`Ghazala D. O'Keefe, MD, Aniruddha Agarwal, MD, Koushik Tripathy, MD (AIIMS), FRCS (Glasgow), Alan Palestine,
`MD, Jennifer I Lim MD
`
`Assigned editor:
`
`Ghazala D. O'Keefe, MD, Pooja Bhat MD
`
`Review:
`
`Assigned status Up to Date
`
` by Ghazala D. O'Keefe, MD on December 4, 2021.
`
`Contents
`1 Disease Entity
`
`1.1 Disease
`1.2 History
`1.3 Denitions
`1.4 Epidemiology
`1.5 Classication
`1.6 Stages
`1.7 Pathophysiology
`
`2 Diagnosis
`
`2.1 History
`2.2 Physical examination
`2.3 Signs
`2.4 Symptoms
`2.5 Clinical diagnosis
`2.6 Ancillary Tests
`2.7 Laboratory test
`2.8 Differential diagnosis
`2.9 Disease Monitoring
`
`3 Management
`
`3.1 Medical therapy
`3.2 Miscellaneous therapy
`
`Retinal Vasculitis
`
`ICD (http://en.wikipe
`dia.org/wiki/Internat
`ional_Statistical_Clas
`sication_of_Disease
`s_and_Related_Healt
`h_Problems)-10 (htt
`p://en.wikipedia.org/
`wiki/ICD-10)
`
`ICD (http://en.wikipe
`dia.org/wiki/Internat
`ional_Statistical_Clas
`sication_of_Disease
`s_and_Related_Healt
`h_Problems)-9 (htt
`p://en.wikipedia.org/
`wiki/List_of_ICD-9_c
`odes)
`
`OMIM (http://en.wiki
`pedia.org/wiki/OMI
`M)
`
`H (http://en.wikipedia.or
`g/wiki/ICD-10_Chapter_
`VII:_Diseases_of_the_ey
`e,_adnexa)35.0 (http://ap
`ps.who.int/classication
`s/icd10/browse/2010/en
`#/H35.0)
`
`362.18 (http://www.icd9
`data.com/getICD9Code.
`ashx?icd9=362.18)
`
`192315 (http://omim.or
`g/entry/192315)
`
`4 References
`
`Disease Entity
`Retinal vasculitis ˈ ɛ ɪˌ ə
`
`ICD-9
`
`ʊˈ ɪ ɪ
`
` is recognized by the following codes as per the International Classication of Diseases (ICD) nomenclature:
`
`ICD 9 Data (http://www.icd9data.com/2013/Volume1/320-389/360-379/362/362.18.htm)
`362.18 Retinal Vasculitis
`
`ICD-10
`
`ICD 10 Data (http://www.icd10data.com/ICD10CM/Codes/H00-H59/H30-H36/H35-/H35.063)
`H35.061 Retinal Vasculitis, right eye
`H35.062 Retinal Vasculitis, left eye
`H35.063 Retinal Vasculitis, bilateral
`H35.069 Retinal Vasculitis, unspecied eye
`
`External Links
`
`MeSH Website (http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?eld=uid&term=D031300)
`Disease Database (http://www.diseasesdatabase.com/ddb13750.htm)
`OMIM (http://www.omim.org/entry/192315)
`Disease
`Retinal vasculitis can be an isolated condition or a complication of local or systemic inammatory disorders characterized by inammation of the retinal
`vessels. It is a sight-threatening condition associated with various infective, auto-immune, inammatory or neoplastic disorders.
`
`Exhibit 2144
`Page 01 of 09
`
`

`

`History
`The concept of retinal vessel inammation was introduced by John Hunter (Figure 1) in 1784, in the report ‘Observations on the inammation of the internal
`[1]
`coats of the veins’.
` Since then, there have been various epidemiological, imaging and clinico-pathological studies to improve the understanding of this
`condition. Since the inammation of the retinal vessel wall is clinically visible, there has been a lot of interest generated in literature to study this disease.
`[2]
`Initially, retinal vasculitis was thought to be an extension of the systemic disease.
` However, there are major differences between the two, because of the
`[3]
`unique microstructure of the retinal vessels. As an example, unlike systemic vasculitis, retinal vasculitis is not associated with vascular necrosis.
`Definitions
`Retinal vasculitis is used as a descriptive term to explain a conglomerate of typical clinical
`[4][5]
`manifestations including perivascular sheathing or cufng, vascular leakage and/or occlusion.
`It may be associated with signs of retinal ischemia, including cotton-wool spots and intra-retinal
`hemorrhage. Involvement of retinal veins due to inammation is termed as phlebitis whereas
`[6]
`retinal arteriolar involvement is termed as arteriolitis.
`Epidemiology
`Retinal vasculitis may be associated with a variety of clinical conditions. Typically, a retinal
`vasculitis would occur as a part of an ocular or systemic disease. Rarely, it may be isolated,
`idiopathic condition, termed as idiopathic retinal vasculitis. It may also present as an initial
`manifestation of an underlying disorder. Isolated retinal vasculitis is seen in approximately 3% of
`[7]
`[8]
`the cases diagnosed with uveitis.
` The annual incidence of retinal vasculitis is 1-2 per 10,000.
` In
`one series, approximately 55% patients with retinal vasculitis had associated systemic
`[1][9]
`inammatory disease.
` In another larger series including more than 1300 patients, retinal
`vasculitis was seen in approximately 15% patients with uveitis. In this series, systemic vasculitis
`[3]
`was associated with retinal vasculitis in only 1.4% cases.
`
`Retinal vasculitis may be more common in individuals under the age of 40, with a slight
`[1][7]
`preponderance in females.
` The mean age of diagnosis of retinal vasculitis is 34 without any
`[2]
`gender differences.
` This disorder is usually bilateral and is visual threatening. As many as one-
`third patients may suffer from severe visual loss (<20/200) as a result of retinal vasculitis and its
`[10][11]
`complications.
`
`[12][13]
`Retinal vasculitis may be associated with a number of systemic and local diseases (Table 2).
`
` John Hunter (1728 – 1793) was a distinguished
`
`Scottish surgeon, anatomist and teacher. He advocated
`careful observation and scientic approach to diseases, which
`led him to recognize and coin the term, ‘retinal vasculitis’. 
`
`Classification
`Systemic vascultis has been classied by the 2012 International
`Chapel Hill Consensus Conference on the Nomenclature of
`[14]
`Vasculitides.
` The details of this classication can be found at
`
`http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029362/pdf/nihms528151.pdf.
`
`The retinal vasculitis may be divided by the
`
`1. Predominantly involved vessels
`Artery- acute retinal necrosis (ARN), idiopathic retinal vasculitis, aneurysm and neuroretinitis (IRVAN), systemic lupus erythematosus (SLE),
`polyarteritis nodosa (PAN), Syphilis, progressive outer retinal necrosis (PORN) and Churg Strauss Syndome
`Vein- Eales' disease, intermediate uveitis, sarcoidosis, multiple sclerosis, tuberculosis, Birdshot chorioretinitis, HIV paraviral syndrome
`
`Exhibit 2144
`Page 02 of 09
`
`

`

`Both artery and vein- Frosted branch angiitis, toxoplasmosis, relapsing polychondritis, granulomatosis with polyangiitis (formerly Wegener's), Chron's
`disease
`2. Involvement of peripheral vessels or vessels around the posterior pole.
`Stages
`The retinal vasculitis has been classically divided into
`
`1. Stage of inammation- This denotes active inammation and is clinically denoted by perivascular segmental whitish inltrates with fuzzy borders (cufng),
`retinal edema, retinal hemorrhages, cystoid macular edema, in some cases snow balls in the vitreous, inammatory vascular occlusions (the blockage of
`veins may not is at the area of active vasculitis which may not correspond to the arteriovenous junction). Active choroiditis (eg. Birdshot chorioretinitis),
`retinitis (eg. Cytomegaloviral retinitis, ), intermediate uveitis, and anterior uveitis (panuveitis) may also be seen. The ocular disease or systemic disease
`causing the retinal vascultiis should be treated as per protocol. Infectious causes shouid be ruled out and treated as necessary. Unilateral noninfectious
`retinal vasculitis involving posterior pole, causing cystoid macular edema or visual decline is treated with periocular steroid (posterior subtenon
`triamcinolone, PST or intravitreal triamcinolone) after ruling out glaucoma or steroid response . Oral steroid also remains an option in cases where
`periocular steroid is contraindicated. Role of systemic or local steroid in peripheral noninfectious vasculitis not involving macula is controversial. Bilateral
`active noninfectious retinal vasculitis involving macula may be treated with oral steroid (after ruling out infection) or sequential PST.
`2. Stage of ischemia- It is clinically characterized by sclerosed vessels and tortuous collaterals. Healed paravascular pigmented choroiditic patches may be
`seen. Fluorescein angiogram shows retinal capillary non perfusion (CNP) though neovascularization is not seen. Most ophthalmologists will follow up such
`cases. The collaterals should not be lasered as it may denote a healing response to revascularize the area which suffered ischemia due to inammatory
`retinal venous occlusion.
`3. Stage of neovascularization- This stage most commonly present with vitreous hemorrhage. Laser of the CNP area as denoted by the uorescein angiogram
`is the treatment of choice.
`4. Stage of complications- Complication are nonresolving vitreous hemorrhage , tractional retinal detachment, combined rhegmatogenous and tractional
`retinal detachment, epiretinal membrane, neovascular glaucoma, neovascularization of the iris and others. Managemnt options include vitrectomy,
`ltration surgery and others.
`Pathophysiology
`[2][5][6]
` In order to
`Despite precise clinical visualization of the retinal microvasculature, the exact pathophysiological mechanism of this condition is not clear.
`[15]
`understand the pathogenesis of retinal vasculitis in humans, experimental animal models have been prepared.
` The manifestations of vascular sheathing and
`[16]
`cufng led to the belief that retinal vasculitis results due to type III hypersensitivity reaction.
` However, there is no proven human or animal model to support
`[17]
`this hypothesis.
` A breakdown of blood-retinal-barrier secondary to intraocular or systemic inammation resulting in clinical features of this disease is more
`likely. Due to the characteristic perivascular location of the inammation, terms such as perivasculitis and periphlebitis have been suggested to denote the
`[6]
`underlying pathology.
`
`Studies demonstrate presence of either a focal, segmental or diffuse retinal perivascular proliferation of lymphoplasmacytic inltrates in eyes with retinal
`[18]
`vasculitis.
` In granulomatous diseases such as sarcoidosis, there may be a collection of numerous epithelioid cells. In eyes with intermediate uveitis and
`[19]
`retinal vasculitis secondary to lymphoma, histopathological studies demonstrate presence of lymphocytic cufng with mural involvement of retinal veins.
`[8][20]
`Characterization of lymphocytic cells in the perivascular region reveals predominance of CD4+ T cells as compared to CD8+ T cells or B lymphocytes.
`[21][22][23]
`There is an upregulation of various inammatory cellular markers including integrins and cell adhesion molecules.
` Increased expression of cell
`adhesion molecules along retinal vessels and blood-retinal-barrier cells may play an important role in inammatory cell recruitment. The sera of patients with
`retinal vasculitis demonstrate an increase in the levels of type 1 interferons, mainly interferon-β. Other molecules that are up-regulated include E-selectin and
`[24]
`s-intracellular adhesion molecules.
`
`Although there is a large pathological diversity among the retinal vasculitis etiologies, the manifestations of inammatory changes resemble in many ways. In
`[25]
`patients with infective retinal vasculitis, culture of live organisms such as mycobacteria may be possible from various systemic foci.
` Infectious organisms
`may involve retinal vasculature by various mechanisms, apart from direct vascular endothelial injury. They may result in release of toxins and may up-regulate
`[26]
`molecules such as heat-shock proteins (HSPs).
` Molecular mimicry may result in aberrant activation of immunological pathways resulting in pathological
`[8]
`manifestations.
`
`In a subset of patients with retinal vasculitis, there is occlusion of blood ow through the retinal vessels. The pathology of occlusive retinal vasculitis may be
`distinct from vasculitis without evidence of obliteration of blood ow. Available literature suggests that eyes with occlusive vasculitis have a poorer prognosis
`with a higher number of complications such as cystoid macular edema (CME), neovascularization and epiretinal membrane formation. A case of retinal
`occlusive vasculitis diagnosed on uorescein angiography is shown in Figure 2. Various etiologies associated with occlusive vasculitis are listed in Table
`[27][28][29]
`3.
`
`Diagnosis
`History
`Retinal vasculitis can affect individuals with all ages and either sex. Cases of retinal vasculitis have been associated with various diseases that can affect any
`race or ethnicity. The patients of idiopathic retinal vasculitis, however, are typically young adults without any signs or symptoms of underlying ocular or
`[2]
`systemic disease.
`Physical examination
`Examination of patients with retinal vasculitis is performed using both, slit-lamp biomicroscopy with 90 or 78-diopter lens and indirect ophthalmoscopy with
`either 20 or 28-diopter lens. The location of the vasculitis may be in the posterior pole or far periphery; hence, scleral indentation must be performed to
`carefully examine the pars plana and ora serrata.
`Signs
`Retinal vasculitis presents with characteristic features on clinical examination. The area of vascular involvement can be focal, diffuse or segmental. Often,
`[12]
`[30]
`retinal vasculitis may involve the veins alone.
` Retinal arteritis is more common with disease such as acute retinal necrosis and systemic vasculitidis.
`There
`are various manifestations of retinal vasculitis, as listed below.
`
`Perivascular sheathing The classic feature of retinal vasculitis is presence of sheathing around the vessel wall. The perivascular sheathing is a collection of
`exudation consisting of inammatory cells around the affected vessels. This results in appearance of a white cuff around the blood vessels. Retinal vascular
`[31][32]
`sheathing is a common manifestation described with clinical entities like multiple sclerosis and Eale’s disease.
` Sarcoidosis can be associated with
`[33]
`exuberant retinal perivascular inltrates that give an impression of ‘candle-wax drippings’.
` Vascular sheathing associated with intraocular tuberculosis is
`depicted in Figure 3.
`
`[34]
`Intraretinal inltrates Patches of retinitis may accompany retinal vasculitis. These are seen in individuals with Adamantiades-Behçet’s disease (ABD)
` and
`[35]
`infectious uveitis.
` These patches of retinitis may be transient, as in ABD, or may be accompanied by retinal necrosis. Intraretinal inltrates can be sight-
`threatening and can lead to retinal atrophy, breaks and detachment. Cytomegalovirus retinitis associated with retinal vasculitis is shown in Figure 4.
`
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`Page 03 of 09
`
`

`

`Cotton-wool spots Retinal vasculitis may result
`in micro-infarcts of the retinal nerve ber layer
`that manifests as diffuse, uffy, cotton-wool like
`[1][12]
`spots in the supercial retinal surface.
`Systemic vasculitidis such as systemic lupus
`[36]
`[37]
`erythematosus,
` polyarteritis nodosa,
`[38]
`Churg-Strauss syndrome
` can be associated
`with retinal precapillary arteriolar occlusion
`resulting in cotton-wool spots. An increase in the
`number of cotton-wool spots may signify a are-
`up of the uveitis.
`
`Retinal Necrosis Infectious forms of uveitis
`associated with retinal vasculitis can be
`associated with necrosis of retinal layers. This is
`[39]
`commonly seen in eyes with toxoplasmosis,
`[40]
`viral infections such as varicella zoster
` or
`[41]
`[42]
`herpes simplex,
` cytomegalovirus
` and
`[43]
`human T-cell lymphoma virus type 1.
`Toxoplasmosis is often associated with
`reactivation of the retinal lesion adjacent to a
`[44]
`previous scar. Kyrieleis arteriolitis
` is an
`accumulation of periarteriolar exudates in eyes
`with toxoplasmosis leading to retinal necrosis
`(Figure 5). Foci of chorioretinitis and choroiditis
`may be closely associated with retinal vasculitis.
`Association of retinal vasculitis and chorioretinal
`lesions in cytomegalovirus retinitis gives an
`appearance of pizza-pie retinopathy (Figure 4).
`
`Frosted Branch Angiitis Frosted branch angiitis is
`a descriptive term for retinal vasculitis
`characterized by severe inltration of
`perivascular space with
`[45]
`lymphoplasmacytic inltrates.
` This
`gives an appearance of frosted branches
`of a tree. This condition can be associated
`with lymphoproliferative diseases such as
`[46]
`lymphoma or leukemia (Figure 6),
` due
`to accumulation of malignant cells.
`However, frosted branch angiitis has also
`been reported in systemic lupus
`[47]
`[48]
`erythematosus,
` Crohn’s disease,
`[49]
`[50]
`toxoplasmosis
` and AIDS.
`
` Fluorescein angiography of a patient with occlusive vasculitis. The vessels of the lower arcade show
`
`inammation denoted by leakage of the vessel wall. There is an extensive area of capillary non-perfusion
`t d by dott d qu r ) ugg tiv of oblit r tion of blood ow' 
`down tr m (d m r
`
`Retinal Ischemia Occlusion of retinal
`vasculature secondary to inammation
`may result in ischemia of the retina and
`development of capillary non-perfusion
`areas (Figure 2). These patients may be
`more predisposed
`to develop
`complications
`arising out of
`retinal non-
`perfusion, such as
`neovascularization
`and intraocular
`hemorrhage.
`Retinal ischemia is
`commonly seen
`following
`[51]
`tuberculosis
` or
`systemic lupus
`[52]
`erythematosus.
`Inammatory
`branch retinal
`arteriolar occlusion
`may be associated
`[53]
`with ABD.
`Retinal vasculitis
`may be associated
`with sclerosis and
`attenuation of the
`vessel wall. This may result in development of a signicant area of retinal non-perfusion. Various other complications that can result include rubeosis, tractional
`retinal detachment, neovascular glaucoma and recurrent vitreous hemorrhage.1
`Symptoms
`[1][54]
`Patients with retinal vasculitis present with the following symptoms (Table 4):
`Clinical diagnosis
`Diagnosis of retinal vasculitis is usually clinical and supported by ancillary tests including uorescein angiography. The signs of retinal vasculitis on fundus
`examination are protean.
`Ancillary Tests
`Fluorescein Angiography Fundus uorescein angiography is the most informative imaging modality in patients with retinal vasculitis. Fluorescein angiography
`[54]
`is routinely used in the diagnosis, monitoring and management of patients with retinal vasculitis.
` Signs on angiography, such as vascular leakage and macular
`edema can help assess the activity of the disease. Leakage of dye from vascular compartment results in perivascular hyperuorescence. The normal retinal
`
` Fundus photographs of two patients with extensive vascular sheathing secondary to intraocular tuberculosis. Panel A demonstrates vascular
`
`sheathing accompanied by intraretinal hemorrhages. In Panel B, there are extensive perivascular hemorrhages in all four quadrants. 
`
`Exhibit 2144
`Page 04 of 09
`
`

`

`vascular ow
`and uorescence
`is demonstrated
`in the video 1.
`
`
` Image shows fundus photograph of a patient
`diagnosed with intraocular toxoplasmosis. There is
`presence of retinal vasculitis with segmental
`sheathing in the periphery. 
`
` Fundus photograph shows characteristic lesions of cytomegalovirus retinitis
`
`associated with vascular sheathing. The dotted square demonstrates an area of segmental
`vascular inammation. Retinitis and intraretinal hemorrhages are seen nasally.
`
` Image shows a montage view of a patient with leukemia presenting
`
`with diffuse retinal vasculitis. The morphological appearance of the retinal
`vessels is called frosted branch angiitis. 
`
`Exhibit 2144
`Page 05 of 09
`
`

`

`FFA video
`
`Thefindingsof retinal vasculitis on fluorescein angiography are summarizedin Figure8.
`
`Vascular leakage Dueto inflammation and breakdownof the blood-retinal-barrier, fluorescein angiographyin eyes with retinal vasculitis can demonstrate a
`diffuse, segmental or focal vascular leakage. In addition, there may be evidence of capillary dropout due to occlusion of blood flow (Figure 2). This can lead to
`growthof new,leaky vessels. The pattern of leakage may vary depending uponthe etiology. The leakage may belimited to arterioles in cases with systemic
`vasculitidis or viral infections. However, venular leakage is the more commonpatternofretinal vasculitis.54! Often, the vascular leakage maybe peripheral.
`Conventional fundus cameras can capture only the central 30° or 50° field of view. Ultra-widefield imaging of the fundusallowstheclinician to obtain more
`informationcompared to regularfield scans (Figure 7). The use of ultra-widefield imaging can alter decision-making in more than 50% patients withretinal
`
`vasculitis.
`
`
`
`Capillary Non-
`perfusion Retinal
`ischemia is a
`feature of a
`subsetof patients
`with retinal
`vasculitis. This
`presents on
`fluorescein
`angiography as
`areasof capillary
`dropout. Behcet’s
`diseaseis
`characterized by
`ischemic branch
`vascular
`occlusion.[5¢! The
`areas of non-
`perfusion may be
`in the peripheryor in the macula. Macular ischemia results in poorer visual outcome despite successful control of inflammation.
`
`Figure 7: Image showing ultra-widefield (200°) fundus photography using Optos P200 (Optos, Scotland, UK) (Panels A and B) and conventional fundus
`photography (50°) with Zeiss FF450 (Carl Zeiss Meditech, Dublin, CA, USA) (Panel C). The superotemporal inflamed vesselis clearly demonstrated on
`wide-field imaging.
`
`Retinal Neovascularization Retinal ischemia and inflammation can result in release of vascular endothelial growth factor (VEGF)that stimulates new vessel
`proliferation. New vessels can be found at the optic disc or elsewhere onthe retina. Patients with extensive retinal ischemia and capillary non-perfusion may
`require scatter laser photocoagulation.
`
`Macular edemaPatients with active retinal vasculitis may have reduced visual acuity due to presence of macular edema.Retinal thickening can be observed on
`fluorescein angiography as leakage of dye in the macula or presenceofa diffuse hyperfluorescence increasing towardsthe late phase. There may be an
`increase in the macular leakage following laser photocoagulation performedforretinal ischemia.
`
`Optic Nerve Head Inflammation Retinal vasculitis may be associated with optic nerve head hyperfluorescence (Figure 8C). There maybe staining of the optic
`nerve headin the late frame. This must be differentiated from optic nerve head leakage secondary to neovascularization.
`
`Choroidal Vascular flow Choroidal vascular flow can be imaged using Indocyanine green angiography (ICG). Patients with retinal vasculitis may have an
`abnormal choroidal blood flow.!57! ICG angiography mayassist in imaging abnormalchoroidal flow patterns such as choroidal neovascularization or
`retinochoroidal anastomosis.
`
`Laboratory test
`
`Exhibit 2144
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`
`

`

`The differential diagnoses of
`retinal vasculitis have been
`listed in Table 2. There are
`various ocular and systemic
`etiologies that can present
`with retinal vasculitis. In a
`subgroup of patients without
`any underlying ocular or
`systemic cause, it is referred
`to as idiopathic retinal
`vasculitis.
`Disease
`Monitoring
`Patients with retinal vasculitis
`must be periodically examined
`to evaluate the extent and
`severity of vascular
`[59]
`leakage.
` The disease
`course can be effectively
`monitored using uorescein
`angiography. Wide-eld
`techniques assist the clinician
`to assess peripheral vascular
`lesions and aid in guiding
`further therapy. Infectious
`retinal vasculitis can be
`monitored by determining the
`load of the causative
`organisms using techniques
`such as quantitative
`polymerase chain
`[60][61][62]
`reaction.
` As retinal
`vasculitis may be early
`manifestation of generalized
`vasculitis of the central
`nervous system (CNS), one
`needs to remember to
`evaluate and monitor the CNS
`
` Fluorescein angiography of patients diagnosed with retinal vasculitis. Panel A shows ultra-wide eld uorescein angiography of a
`
`patient with diffuse retinal vasculitis and leakage, more in the nasal and temporal periphery. Panel B shows late frame angiogram of a
`patient diagnosed with idiopathic unilateral retinal vasculitis. There is perivascular leakage in the periphery (temporal > nasal quadrant).
`Panel C shows diffuse perivascular leakage in the temporal periphery of a patient diagnosed with multifocal choroiditis. There is
`hyperuorescence at the superotemporal perivascular region due to staining of the choroiditis lesion. Panel D shows diffuse leakage from
`small vessels at the macula in a patient diagnosed with panuveitis. 
`
`vasculature (i.e. employing magnetic resonance imaging with contrast) as well when
`[63]
`indicated.
`
`Management
`
`The management of retinal vasculitis depends on the underlying etiology. Adequate
`control of the intraocular inammation is sine qua none for achieving remission of
`retinal vasculitis. This disease can be recurrent and aggressive in its course requiring
`[6]
`steroid and immunosuppressive therapy.
` Ocular sequelae resulting from
`uncontrolled retinal vasculitis can have deleterious consequences including severe
`visual loss.
`
`The mainstay of therapy for retinal vasculitis is medical management. Infectious
`etiology must be ruled out as the treatment for non-infectious disease consists of
`immunosuppressive therapy, which can possibly worsen intraocular infections.
`Medical therapy
`Non-infectious retinal vasculitis is managed by systemic or local corticosteroids and
`steroid-sparing immunosuppressants. The local delivery of therapeutic agents can be
`done via intravitreal injections or periocular therapy, although the latter may not be
`sufciently adequate for cases of severe retinal vasculitis. The choice of
`immunosuppressive agents must be tailored based on ocular manifestations,
`etiology and systemic co-morbidities. Use of advanced imaging techniques such as
`ultra-wide fundus photography and uorescein angiography can aid in the
`[55][59]
`management of patients with retinal vasculitis.
`
`In a series of 56 patients with non-infectious uveitis, systemic prednisone (oral) was
`used for the treatment of two-third patients at an average dose of 27mg/day for a
`[1]
`mean of 14 months.
` Another study from Eastern India revealed that oral steroids
`[64]
`were used in more than 80% patients with retinal vasculitis.
` In addition,
`periocular and intraocular steroids such as triamcinolone have been used in
`[65][66][67]
`vasculitis associated with pars planitis.
` However, administration of steroid-
`sparing immunosuppressants are recommended in cases requiring more than
`[68]
`10mg/day dose of oral prednisone.
`
`Unlike systemic vasculitis that can be managed with colchicines and non-steroidal anti-inammatory agents, retinal vasculitis due to causes such as ABD
`[69]
`requires a more aggressive approach.
` Available immunosuppressive agents include cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil
`[70][71]
`or biologic agents such as iniximab or etanercept. Cyclosporine has been used as a drug of choice in previous studies.
` In eyes with vasculitis associated
`[72][73][74]
`with birdshot chorioretinopathy, sarcoidosis and Harada’s disease, azathioprine has been used for treatment.
` Alkylating agents such as chlorambucil
`[1]
`and cyclophosphamide have also been used in combination with corticosteroids.
` Biologic agents have been increasingly used to achieve remission in eyes
`[75]
`with retinal vasculitis.
` These include iniximab, tacrolimus and adalimumab, apart from other agents targeting molecules such as tumor necrosis factor and
`interleukins.
`
`Infectious retinal vasculitis must be treated with appropriate anti-microbial agents depending upon the etiology. Infectious retinal vasculitis is a heterogenous
`cohort with various causative organisms such as bacteria, viruses and parasites (Table 2). Anti-microbial therapy, including oral and intravitreal injections in
`various combinations with steroids have been used for the treatment of these disease entities.
`Miscellaneous therapy
`
`[ ]
`
`Exhibit 2144
`Page 07 of 09
`
`

`

`[6]
`Apart from immunosuppression, various therapeutic options such as pan-retinal photocoagulation have been tried in order to control retinal vasculitis.
`[76]
`Cryotherapy has been used in the past to treat retinal vasculitis associated with pars planitis in the past.
` Mesenchymal stem cell therapy (MSCT) has been
`[77]
`used without success in eyes with ABD to control the retinal vasculitis.
`
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