UVEITIS – BASICS AND

TERMINOLOGIES

Dr. Krati Gupta Dr. Saurabh Deshmukh www.eyelearn.in

Dr. Krati Gupta | Dr. Saurabh Deshmukh

UVEITIS

• Several schemes for the classification of uveitis currently exist. Various methods are based on 1. anatomy (the portion of the uvea involved), 2. clinical course (acute, chronic, or recurrent), 3. etiology(infectious or noninfectious), 4. histology (granulomatous or nongranulomatous)

• Standardization of Uveitis Nomenclature (SUN) Working Group in 2005 developed 1. an anatomical classification system, 2. descriptors, 3. standardized grading systems, 4. and terminology

• The SUN Working Group recognized that clinical scenarios exist in which both anterior chamber and vitreous inflammation are present but the vitritis is more than expected in an isolated anterior uveitis.

• These cases should be referred to as “anterior and intermediate uveitis” and not as “panuveitis”.

• Remission is defined as inactivity -no visible cells for 3 months or longer.

Dr. Krati Gupta | Dr. Saurabh Deshmukh

Anterior uveitis- iris and anterior part of ciliary body (pars plicata) Anterior chamber inflammation Iritis Retrolental (anterior vitreous) Iridocyclitis Inflammatory processes that originate in the cornea with secondary involvement of the anterior chamber are called

keratouveitis

If the inflammatory reaction involves the sclera and uveal tract Sclerouveitis. Intermediate uveitis - Inflammation in this middle portion (posterior ciliary body, pars plana) of the eye Idiopathic intermediate uveitis Pars planitis Manifests primarily as floaters affecting vision; The eye frequently appears quiet externally. Vision loss is primarily a result of chronic cystoid macular edema (CME) or, less commonly, cataract formation

Retinal Vasculitis • Retinal vasculitis is defined by the presence of retinal vascular changes in association with ocular inflammation. • The term is used in distinction to vasculopathy, in which there are vessel changes but no visible evidence of inflammation. • Blood vessel changes include perivascular sheathing and vascular leakage or occlusion shown on fluorescein angiography

studies. • Peripheral retinal vasculitis may be observed in intermediate uveitis but is not sufficient for the anatomical classification of

posterior/panuveitis, whereas diffuse retinal vasculitis is sufficient.

• Nongranulomatous inflammation typically has a lymphocytic and plasma cell infiltrate, whereas • Granulomatous reactions also include epithelioid and giant cells. • Discrete granulomas are characteristic of sarcoidosis; • Diffuse granulomatous inflammation appears in Vogt-Koyanagi-Harada (VKH) syndrome and sympathetic ophthalmia. • Zonal granulomatous disease can be observed in lens induced uveitis.

The chemical mediators involved in inflammation result in

1. vascular dilation (ciliary flush), 2. increased vascular permeability (aqueous flare), 3. and chemotaxis of inflammatory cells into the eye (aqueous and vitreous cellular reaction)

Dr. Krati Gupta | Dr. Saurabh Deshmukh

Anterior segment

1. Ciliary flush/ injection

Perilimbal vascular engorgement (ciliary flush) or diffuse injection of the conjunctiva, episclera, or both is typical with acute anterior uveitis.

2. Keratic precipitates

Keratic precipitates are collections of inflammatory cells on the corneal endothelium. When newly formed, they tend to be white and smoothly rounded, later transitioning to crenated (shrunken), pigmented, or glassy. Large yellowish KPs are called mutton-fat KPs and are usually associated with granulomatous types of inflammation.

3. AC reaction With increased capillary permeability, the anterior chamber reaction can be described as serous (aqueous flare caused by protein influx) purulent (polymorphonuclear leukocytes and necrotic debris causing hypopyon) fibrinous (plasmoid, or intense fibrinous exudate) sanguinoid (inflammatory cells with erythrocytes, as manifested by hypopyon mixed with hyphema)

4. Inflammatory cells

SUN working group grading of AC cells

5. Flare SUN working group grading of AC flare 6. Hypopyon,

Fibrin White purulent exudate composed of myriad of inflammatory cells

7. Pigment dispersion

8. Pupillary miosis Due to pupillary spasm predisposes to formation of posterior synechiae 9. Iris nodules Koeppe nodules at the pupillary border,

Busacca nodules within the iris stroma, Berlin nodules in the angle Yellowish nodules from dilated iris vessels (Roseola) in syphilis Iris pearls in lepromatous CAU Iris crystals(Russell bodies) CAU, FUS Iris granulomas, heterochromia (eg, Fuchs heterochromic uveitis), or stromal atrophy (eg, herpetic uveitis).

10. Synechiae Iris involvement may manifest as either anterior or posterior synechiae 11. Band

keratopathy

12. IOP With uveitic involvement of the ciliary body and trabecular meshwork, intraocular pressure (IOP) is often low, secondary to decreased aqueous production or increased uveoscleral outflow, but IOP may increase precipitously if the meshwork becomes clogged by inflammatory cells or debris or if the trabecular meshwork itself is the site of inflammation (trabeculitis). Pupillary block with iris bombé and secondary angle closure may also lead to an acute rise in IOP.

Dr. Krati Gupta | Dr. Saurabh Deshmukh

Intermediate segment

• Signs in the intermediate anatomical area of the eye include vitreal inflammatory cells, which are graded in density from 0 to 4+:

• The SUN group did not achieve consensus regarding a grading system for vitreous cells. • The vitreous grading scale shown here was used in the Multicenter Uveitis Steroid Treatment Trial. • Vitreous cells are typically graded by observing the retrolental space in a dilated eye using the slitlamp biomicroscope and a

1- × 0.5-mm beam. • The consensus is that cells in the vitreous strands are old, and cells in the syneretic areas may be new. • The National Institutes of Health (NIH) grading system for vitreous haze, which was adopted by the SUN group, may be a

better indicator of disease activity than cell counts alone. • With this method, standardized photographs are used for comparison with clinical images to ultimately arrive at the level of

vitreous haze. • Additional uveitic changes may be observed in the vitreous, namely,

1. Snowball opacities, which are common in sarcoidosis or intermediate uveitis 2. Exudates over the pars plana (snowbank).

Ø Active snowbanks have a fluffy or shaggy appearance. Ø As pars planitis becomes inactive, the pars plana appears gliotic or fibrotic and smooth; thus, these changes are not

referred to as snowbanks. 3. vitreal strands

• Chronic uveitis may be associated with cyclitic membrane formation, secondary ciliary body detachment, and hypotony.

Posterior Segment • Signs in the posterior segment of the eye include

1. retinal or choroidal inflammatory infiltrates 2. inflammatory sheathing of arteries or veins 3. exudative, tractional*, or rhegmatogenous* retinal detachment 4. retinal pigment epithelial hypertrophy or atrophy* 5. atrophy or swelling of the retina, choroid, or optic nerve head* 6. preretinal or subretinal fibrosis* 7. retinal or choroidal neovascularization*

• An asterisk is used to indicate structural complications. Retinal and choroidal signs may be unifocal, multifocal, or diffuse.

Dr. Krati Gupta | Dr. Saurabh Deshmukh

Review of the Patient’s Health and Other Associated Factors • Although ocular inflammation may be an isolated process involving only the eye, it can also be associated with a systemic

condition. • However, ocular inflammation frequently does not correlate with inflammatory activity elsewhere in the body, so it is

important for the clinician to carefully review systems. • In some cases, the uveitis may actually precede the development of inflammation at other body sites. • Immunocompromised, use of intravenous drugs, hyperalimentation, and certain occupations are just a few risk factors that

can direct the investigation.

Dr. Krati Gupta | Dr. Saurabh Deshmukh

Differential diagnosis

1. Infectious agents (viruses, bacteria, fungi, Protozoa, and helminths)

2. Noninfectious entities of presumed immunologic or allergic origin, masquerade syndromes such as Ø endophthalmitis Ø neoplastic disease, Ø and unknown or idiopathic causes,

3. Intraocular lymphoma 4. Malignant melanoma 5. Retinoblastoma, 6. Leukemia 7. Juvenile xanthogranuloma, 8. Pigment dispersion syndrome, 9. Retinal detachment, 10. Retinitis pigmentosa, 11. Ocular ischemia syndrome

Epidemiology • Uveitis is responsible for 10% of all blindness cases in the United States. • The incidence of blindness attributable to uveitis is approximately 15 new cases/100,000 persons per year. • In addition, the incidence and prevalence were lowest in the pediatric age groups (prevalence of 30/100,000) and highest in

those over age 65 years (prevalence of 151.3/100,000). • Females are slightly more commonly affected. • Most cases are chronic and bilateral and carry significant complication rates. • This distribution is generally similar: anterior involvement is most common, followed by panuveitis, then posterior uveitis,

and finally intermediate uveitis.

Investigations • Laboratory testing is not a substitute for a thorough, hands-on clinical evaluation. • Once a list of differential diagnoses is compiled based on the anatomical location and clinical characteristics of the

inflammation, appropriate laboratory tests can be ordered. • At a minimum, most uveitis specialists will employ a few studies—purified protein derivative (PPD) skin test or interferon-

gamma release assay, syphilis serologic testing, and chest radiograph—as part of their initial evaluation of uveitis.

Dr. Krati Gupta | Dr. Saurabh Deshmukh

1. FA CME; retinal vasculitis; secondary choroidal or retinal neovascularization; Areas of optic nerve, retinal, and choroidal inflammation can all be detected angiographically. Retinochoroidopathies, or white dot syndromes, have characteristic appearances on FA.

2. Fundus autofluorescence imaging

is a noninvasive modality that utilizes the fluorescent properties of lipofuscin to assess the viability of the retinal pigment epithelium (RPE)–photoreceptor complex in inflammatory chorioretinopathies that involve the outer retina, RPE, and inner choroid.

3. Indocyanine green angiography

It may show 2 patterns of hypofluorescence in the presence of inflammatory choroidal vasculopathies. Type 1, which represents more selective inflammatory choriocapillaropathies, demonstrates early and late multifocal areas of hypofluorescence and may be observed in multiple evanescent white dot syndrome (MEWDS). Type 2 represents stromal inflammatory vasculopathies of the choroid and demonstrates areas of early hypofluorescence and late hyperfluorescence; it may be observed in sarcoidosis, sympathetic ophthalmia, birdshot uveitis, and VKH syndrome.

4. Ultrasonography can be useful in demonstrating vitreous opacities, choroidal thickening, retinal detachment, and cyclitic membrane formation, as well as for ruling out occult foreign bodies, particularly if media opacities preclude a view of the posterior segment.

5. Electroretinography Can be used along with visual field studies to monitor progression of birdshot uveitis and, occasionally, to rule out retinitis pigmentosa as a uveitis masquerade.

6. Optical coherence tomography (OCT) and spectral-domain OCT (SD-OCT)

Are cross-sectional imaging methods using coherent light to develop a low-coherence interferometric image. AS-OCT may be useful to evaluate an eye for retained lens fragments or IOL chaffing in persistent postoperative uveitis and someday may provide an objective means of grading anterior segment cells. OCT has become the standard-of-care method for the objective measurement of uveitic CME, retinal thickening, subretinal fluid associated with choroidal neovascularization, and serous retinal detachments. It can be useful in eyes with smaller pupils but can be limited by media opacities. OCT can be valuable in monitoring patients with uveitic glaucoma. SD-OCT provides a high-resolution image of the retina that is helpful in elucidating morphologic changes in many posterior uveitic and panuveitic entitis

Dr. Krati Gupta | Dr. Saurabh Deshmukh

Anterior chamber paracentesis • Procedure 1. Aqueous humor may be analyzed for diagnostic purposes following anterior chamber paracentesis, 2. It is performed using sterile technique at the slit lamp or with the patient supine on a treatment gurney or chair. 3. Topical anesthetic drops are instilled; the eye is prepared with topical povidone-iodine solution; and a lid speculum is put

in place. 4. A tuberculin (1-mL) syringe is attached to a sterile 30-gauge needle, which is then advanced under direct or slit-lamp

visualization into the anterior chamber through the temporal limbus or clear cornea parallel to the iris plane. 5. As much aqueous is aspirated as is safely possible (usually 0.1–0.2 mL), avoiding the iris and lens. 6. The needle is withdrawn.

• Advantage - Compared with diagnostic vitrectomy, this procedure is much simpler to perform in an office setting. • Disadvantage- When the differential diagnosis of the uveitic entity is broader and a larger ocular fluid sample is required,

vitreous biopsy should be considered. • Complications - Complications of aqueous paracentesis may include anterior chamber hemorrhage, endophthalmitis, and

damage to the iris or lens.

• Uses 1. If infection is suspected, the aqueous specimen should be processed for microbiologic evaluation, Gram stain. 2. Histologic evaluation may be useful if leukemia or lymphoma is suspected, in case of a hypopyon–hyphema combination

that may occur in acute myelogenous leukemic infiltration of the uveal tract. 3. PCR evaluation may be useful in HSV-1 or -2, VZV, CMV, or Toxoplasma species is suspected. 4. Recent studies suggest similar diagnostic sensitivity (81%) and specificity (97%) of aqueous and vitreous samples,

particularly in uveitis caused by HSV-1 and -2, VZV, and CMV. 5. Evaluation of aqueous antibody production based on the Goldmann-Witmer (GW) coefficient is considered the gold

standard for the diagnosis of toxoplasmosis in Europe. 6. Diagnostic yield is increased when results of PCR and the GW coefficient are used together, especially in viral infections. Vitreous biopsy Procedure 1. In selected patients, with carefully planned cytologic, cytofluorographic, and microbiologic examination of vitreous fluid,

can be an effective means of confirming a clinical diagnosis. 2. The procedure is performed via a standard 3-port pars plana vitrectomy. 3. In all these scenarios, undiluted vitreous specimens are typically required for testing. 4. It is possible to obtain 0.5–1.0 mL of undiluted vitreous for evaluation using standard vitrectomy techniques.

Complications of diagnostic vitrectomy in uveitic eyes 1. Can include retinal tears or detachment, suprachoroidal or vitreous hemorrhage, and worsening of cataract or

inflammation. 2. Although vitreous surgery can be therapeutic and diagnostic in cases of uveitis, the pharmacokinetics of delivered

intravitreal drugs are markedly altered in eyes that have undergone pars plana vitrectomy; the half-life of intravitreal corticosteroids, for example, is markedly reduced in vitrectomized eyes.

Uses 1. The most common indications include suspected endophthalmitis, primary intraocular lymphoma or other intraocular

malignancy, and infectious etiologies of posterior uveitis or panuveitis. 2. Chronic uveitis that has an atypical presentation or an inadequate response to conventional therapy may warrant diagnostic

vitrectomy. 3. Specific primers for Toxoplasma gondii, HSV, VZV, and CMV are readily available. 4. Combined with clinical picture, presence of DNA from specific pathogens can be very sensitive & specific in establishing

an etiology. 5. PCR studies may be performed on undiluted vitreous if an infectious posterior uveitis or panuveitis is suspected, but the

differential diagnosis must be narrowed to a few causes because “global” PCR testing would be of little value. 6. If the results of diagnostic vitrectomy (vitreous biopsy) could potentially alter management of the uveitis, it must be

considered. Chorioretinal biopsy 1. It a more technically challenging procedure, may be useful when the diagnosis cannot be confirmed on the basis of clinical

appearance or other laboratory investigations. 2. Rapidly progressive posterior uveitic or panuveitic entities, such as a necrotizing retinitis for which the etiology is

unknown and the therapeutic regimen undetermined, may require chorioretinal biopsy. 3. Suspected intraocular lymphoma confined to the subretinal space is also an indication for a chorioretinal biopsy. 4. This procedure is performed only after all other less-invasive measures, such as serologic, radiologic, and aqueous and

vitreous sample testing, have failed to confirm the diagnosis. 5. It is associated with a high rate of complications and must be performed only by vitreoretinal surgeons with extensive

experience using these techniques