Joseph Sowka, OD, FAAO, Diplomate

Posterior Uveitis Joseph Sowka, OD, FAAO, Diplomate

Symptoms  Blurred vision  Floaters  Pain and photophobia seen in anterior uveitis is not likely to occur

Signs  Mild anterior segment inflammation  External eye typically white and quiet, depending upon etiology  Anterior uveitis  Typically asymptomatic spill-over from posterior chamber  Occasionally granulomatous  Vitritis  Infiltrates  Vascular sheathing  Candlewax drippings  Retinal scarring and RPE hyperplasia  Fuzzy fundus lesions  Inflammatory cell aggregation  Snow balls and snow banks  Periphlebitis  Peripheral retinal neovascularization with attendant complications  CME  Retinitis  Chorioretinitis  Choroiditis

Types of Posterior Uveitis  Traumatic/ surgical  Infectious (syphilis, toxoplasmosis, etc)  Infiltrative (sarcoidosis)  Idiopathic (pars planitis)

Pars Planitis  True intermediate/ posterior uveitis  Younger patients  Chronic  May be asymptomatic  Blurred vision  Visual acuity ranges from 20/20 to no perception of light, with a mean range of 20/40-

1 20/50  Cataracts  Vitreous debris  CME  Pars planitis is typically bilateral, with both eyes affected in 85% of the cases  Seems to have an association with Crohn’s disease and, especially, multiple sclerosis  45% positive association with between pars planitis and multiple sclerosis. You must give strong consideration to ordering MRI of the brain in patients with pars planitis, especially if the patient is in a high risk group  Vitreal cells  Retinal inflammatory exudates (snowballs) and periphlebitis  Inferior snowbanking of exudates  While vitreous snowballs and snow banks are frequently encountered, they are by no means present in every eye with pars planitis and need not be present to make this diagnosis  Exacerbations and remissions  May last for years  Generally benign  Treatment should be conservative and often involves only periodic monitoring, especially if vision is only minimally disturbed by vitritis and CME  This disease has a good prognosis with a final mean visual acuity for patients of 20/30-20/40 in 90% of cases  There are exacerbations and remissions and typically this disorder runs a very long course. Inflammatory mediators will increase vasopermeability of retinal capillaries resulting in posterior segment inflammatory cells as well as CME.

Pars Planitis: Complications  Posterior subcapsular cataracts (both from the disease itself and the treatment)  Posterior vitreous detachment  Frequent cause of rare PVD in young patients  Neovascularization (mostly posterior segment)  Attendant complications of vitreous hemorrhage and tractional RD  Glaucoma (steroid induced, POAG, secondary inflammatory)

Pars Planitis: Treatment  Observation  Periocular, intravitreal, and systemic corticosteroids have all been employed, as well as other immunosuppressive drugs. However, once a commitment to use systemic steroids is made, typically they are used for months. With this treatment come the possible attendant complications of steroid induced cataracts and glaucoma.  Topical steroids only if there is concomitant anterior inflammation  Anterior uveitis in pars planitis is not true anterior uveitis, but a spill over from the posterior segment. These patients are typically asymptomatic.  In severe or unresponsive cases, transscleral cryoretinopexy or thermal laser 2 photocoagulation can be directed against the snowbanks to destroy the inflamed areas along with the infiltrates. These treatments can reduce intraocular inflammation, increase visual acuity, and decrease dependence upon systemic steroids. Vitrectomy can also be used to clear the vitreous of both cells and hemorrhage

Clinical Pearl: When encountering a true PVD in a young patient, look for vitreal cells and other signs of pars planitis.

Toxoplasmosis  Number one cause of posterior uveitis  Number one cause of focal chorioretinitis  Caused by toxoplasma gondii  Obligate intracellular protozoan parasite  Retinal  Hematogenous spread to eye  Neural  Congenital- passed from mother to child transplacentally after acquiring it during pregnancy  Most common mode of transmission  40% likelihood of fetal involvement  Acquired (must consider AIDS)  HIV testing needed  Often without associated scarring  Cat feces and undercooked meat are vectors  Sporozoite (cat)  Tachyzoit (proliferative form in humans)  Bradyzoit (encysted and dormant)  Bradyzoit sits in the NFL  Bradyzoit usually sit near old scars and may remain viable for 25 yrs  Immunosuppression can reactivate a bradyzoit  May spontaneously reactivate without immunosuppression  When active, toxoplasmosis produces a retinitis that appears as  " Headlights in a fog " due to overlying focal vitritis  Arteritis  Periphlebitis  Lesions heal within 3 weeks to 6 months  Affects the posterior pole  Vitritis usually located near an old scar- diagnostic  Encystic organisms latent near old scar

Toxoplasmosis: Ocular Findings  PVD  CME  Retinochoroiditis 3  Scarring  Arteritis  Vasculitis  Papillitis (totally destroys vision)  Vitritis  RD

Toxoplasmosis: Other Thoughts  Activity for 4-6 months  Diagnosed by ELISA Toxoplasmosis titre  Self limiting, but often treated  Lesions which must be treated include large lesions (> 3DD), severe vitritis with vision loss, and juxtafoveal or peripapillary lesions  Results in chorioretinal scarring which may be visually disabling

Toxoplasmosis: Treatment  Often simply monitored if vision not threatened and patient has healthy immune system (i.e., Not HIV/AIDS)  Triple sulfonamide drugs  Sulfadiazine 1 gm PO QID or Bactrim (trimethoprim 160 mg/sulfamethoxazole- 1 Double Strength (DS) or 2 tabs BID) x 6 weeks (most common treatment)  Bactrim DS every third day has shown to significantly reduce ocular toxoplasmosis recurrences.  Pyrimethamine (Daraprim- anti-parasitic)  Causes bone marrow suppression which can be averted with folic acid supplementation  25 mg PO QD x 6 weeks with Folic acid 5 mg Q2 days  Clindamycin 250 mg QID  Toxic and can cause colitis  Spiramycin  Steroids  Prednisone 40 mg QD (only use prednisone in conjunction with the above meds- never alone). Begin antimicrobial therapy for a few days first. Generally not used unless vision significantly threatened.

Clinical Pearl: Though we have long known how to treat toxoplasmosis, it is not clear that we should treat toxoplasmosis. There is a lack of evidence based medicine that identifies treatment benefits. Controlled studies are clearly needed.

Clinical Pearl: Not every black spot on the retina is a toxoplasmosis scar, despite what other optometrists tell you.

Clinical Pearl: The key diagnostic sign of toxoplasmosis is an active vitritis with a "headlights in a fog appearance" adjacent to an area of old scarring.

4 Clinical Pearl: When encountering active toxoplasmosis, especially in a young patient, strongly consider HIV testing.

Toxocariasis  Nematode - parasitic  Puppies, eating dirt (geophagia), eating fecal matter (coprophagia) are the vectors  Occurs in children and is usually unilateral  Larvae travel in blood and lymph fluid  Two forms: Never seen together 1. Ocular  Ages 7-8  Neuroretinitis  Vitritis  Papillitis  RPE changes  Elevated granuloma  Decreased vision  Leukocoria  Chronic endophthalmitis 2. Systemic  Ages 2-5  ELISA  Photocoagulation; cryo  Corticosteroids (oral) for inflammation  Closely related is the disease caused by the blackfly- onchocerciasis

Ocular Histoplasmosis Syndrome  Fungal disease: Histoplasma capsulatum  Associated with bird (pigeon, chicken) feces  Actually in soil fertilized by bird feces  Actually found in bat feces  Ohio - Mississippi River Valley (or any river valley region)  Inhaled fungus  Inhaled mycelial spores of Histoplasma capsulatum  These spores undergo transformation to the yeast phase in the lung, and from here it is disseminated via the bloodstream to the rest of the body (including the eye where it causes choroidal infection)  Flu-like illness  Retinal lesions reactivate 10-30 yrs later  Affects ages 20-50  Rare in patients of African descent 5  Circumpapillary choroidal scarring  Peripheral atrophic Histo spots & peripheral scars  Punched-out lesions  Large (1 DD) or small  Hypo- or-hyperpigmented  Foci of previously present inflammatory reaction  Site of infection with Histoplasma organism  Macular compromise  Granulomatous inflammatory mass  Diagnosis is made by presence of peripapillary scarring and at least one peripheral Histo spot  Invisible choroiditis  Not a fundus finding because it is not visible. May possibly be seen on FA  Due to an accumulation of inflammatory cells at an inflammatory focus  Will eventually result in an atrophic Histo spot

Ocular Histoplasmosis Syndrome: Maculopathy  Macular granuloma  Bruch's disruption  Choroidal neovascularization  4th most common cause of CNVM  Sub-RPE hemorrhage with subsequent disciform scarring  Lipid exudate  Differential diagnosis  Multifocal choroidopathy  Acute posterior multifocal placoid pigment  Multiple evanescent white dot syndrome  Retinal pigment epithelialitis  Serpiginous choroiditis  Diffuse unilateral subacute neuroretinitis

Clinical Pearl: Ocular Histoplasmosis Syndrome can look exactly like multifocal choroidopathy with one exception: OHS never causes cells to appear in the vitreous because it is purely a choroiditis.

Clinical Pearl: Many peripheral spots look like Histo spots. To confirm the suspected diagnosis in these cases, look for associated peripapillary scarring.

Ocular Histoplasmosis Syndrome: Treatment  Routine f/u when inactive  Home amsler to monitor for neovascularization  Oral, depot steroids when active  Some advocate that steroids are ineffective  Photocoagulation for juxtafoveal neo 6  Laser tx is mainstay for Histo  30% recurrence rate for neo regrowth  Risk factors are younger age and females  Neo can spontaneously involute without treatment  PDT commonly used  Anti-angiogenic drugs are used as well  60% of untreated patients develop 20/200 or worse vision  30% chance of fellow eye involvement within 7 yrs

Clinical Pearl: Treatment isn’t directed at the cause of Histoplasmosis, but rather at the neovascular maculopathy using standard methods.

Sarcoidosis  Idiopathic disseminated granulomatous disease  Non-caseating granulomas  May have lid and conjunctival granuloma  Multisystemic  Females > males  Blacks >>> Whites  Ages 20-60 yrs

Sarcoidosis: Ocular Manifestations  Keratoconjunctivitis sicca with lacrimal gland involvement by granuloma  Granulomatous anterior uveitis  Mutton fat KP’s and posterior synechiae  Periphlebitis  Candlewax drippings  More common than retinal granulomas  Adjacent ‘puff balls’  Vitritis/retinitis  Peripheral vascular occlusion and neovascularization  CME  From inflammation  Optic neuropathy  Inflammatory, infiltrative, or compressive optic neuropathy  Disc edema

Sarcoidosis: Diagnosis  Hilar adenopathy (enlarged pulmonary lymph nodes) on chest x-ray (CXR)  Angiotensin converting enzyme (ACE)  Gallium scan  Uptake of gallium only in sarcoidosis after gallium is injected into venous system (uptake in salivary and lacrimal glands and hilar lymph nodes) 7  Conjunctival biopsy or biopsy of skin granulomas

Sarcoidosis: Treatment  Recognition of sarcoid in differential diagnosis  Oral steroids and Periocular steroids

Clinical Pearl: Sarcoidosis should be high on your list of differential diagnoses when encountering retinal periphlebitis. Eales' Disease  Difficult to classify  Vascular occlusion secondary to posterior segment inflammation  Retinal periphlebitis  Idiopathic bilateral periphlebitis affecting retinal veins  Healthy young men in 20's-30's  25% have hearing/balance difficulties  Patient may complain of floaters, but is typically asymptomatic early in the disease  Possibly with associated anterior uveitis  Obscure inflammatory reaction to antigens  High association to tuberculoprotein sensitivity  Retinal findings include perivascular sheathing and capillary non-perfusion  Sufficient capillary non-perfusion can lead to retinal neovascularization with attendant complications  Vitritis occurs overlying periphlebitis  Retinal telangiectasias may occur with resultant retinal/macular edema  Vision reduction can come from retinal/macular edema, vitreous hemorrhage, tractional retinal detachment  In late stages/recovered stages, there is often perivascular scarring/RPE hyperplasia

Eale’s Disease: Management  Rule out tuberculosis  FA if neovascularization is suspected  Focal photocoagulation if macular edema develops from telangiectasias or PRP for retinal/disc neovascularization  Often, the disease self limits

Clinical Pearl: Two key features of Eale's disease are venous peri-phlebitis and venous obstruction.

Clinical Pearl: Eales’ disease targets healthy, young males.

Clinical Pearl: Suspect Eale’s Disease in cases of posterior segment neovascularization, vitreous hemorrhage, tractional detachment in young, healthy males with no history of diabetes. 8 Clinical Pearl: Suspect Eale’s disease when encountering perivascular scarring.

Syphilis:  Caused by spirochetal bacteria Treponema pallidum  Possible ocular findings:  Salt-n-pepper fundus (like RP)  Multifocal area of RPE atrophy  Uveitis (anterior and/or posterior)  Periphlebitis  Vasculitis  Choroiditis  Retinitis  Papillitis or retrobulbar neuropathy  Vitritis  Intraretinal hemorrhage  Peripheral neovascularization and attendant complications  Diagnosis:  Non-specific (RPR, VDRL) and specific (FTA-ABS, MHA-TP) tests  Management:  Systemic antibiosis

Clinical Pearl: Syphilis should be high on your list of differential diagnoses when encountering retinal periphlebitis.

Clinical Pearl: Whenever you see retinal periphlebitis, vasculitis, or candlewax drippings, immediately think of sarcoidosis and syphilis.

Behcet’s Syndrome:  Painful aphthous oral/genital ulcers  Arthritis  Conjunctivitis, anterior uveitis  Endophthalmiitis  Arteritis  Periphlebitis  Necrotizing retinitis  Retinal edema, exudation

Endophthalmitis  Post-surgical  Post-penetrating foreign body  Indwelling catheter as portal of entry for microbes  Rarely endogenous 9  Fungi  Extremely inflamed eye  Hypopyon  Staphylococcus; streptococcus; pseudomonas  Poor prognosis  Intravitreal injections of antibiotics  Eye may be totally lost

“The White Dot Syndromes”

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)  Bilateral with accompanying vision loss (often severe)  Often with viral prodrome several weeks antecedent  Floaters, mild eye pain, metamorphopsia and/or scotomas  Young healthy adults  May have inflammations elsewhere  May have concurrent episcleritis  HLA B27 association  Yellow - white placoid lesions  Cream colored lesions  May be gray  Discrete and flat  May have associated disc swelling (rare)  May have overlying vitritis  May have shallow subretinal fluid over large lesions  Lesions fade within days to leave RPE mottling  RPE and inner choroid affected  Likely a choroidal vasculitis, post viral autoimmune disorder, or may be related to spirochete disease  FA: early hypofluorescence due to blockage, then late staining  Blockage and accumulation in RPE  Resolves within 4 weeks  Recurrence uncommon, but if it does recur, it will do so within 3 months typically  No tx  Prognosis excellent  Pts. generally recover 20/40 or better  May have a (rare) associated CNS vasculitis which is life threatening and requires systemic steroids  Px must be instructed to return immediately if they develop severe HA or other neurological symptoms

Birdshot Retinochoroidopathy 10  Vitiliginous  Chronic disease in healthy middle-aged patients (females)  Bilateral decreased vision (20/50).  Floaters, blurred vision, nyctalopia, field defects  Multiple depigmented, creamy spots in posterior pole following vessels  When fresh, there is ‘substance’, but becomes more atrophic later  RPE hyperpigmentation  Chronic lesions can become confluent and spread to the macula  Vitritis  Disc edema  Retinal vasculitis  Epiretinal membrane formation  CME  Autoimmune disease  (+) HLA A29 highly correlated  Oral steroids  NVD; NVE  FA: filling delay and vessel leakage.  Prognosis is poor due to chronicity

Multiple Effervescent White Dot Syndrome (MEWDS):  Likely a group of disorders  Healthy young patients (typically females)  Viral prodrome  Unilateral, rapid with vision loss  20/200  Photopsia with or within field loss very diagnostic  Markedly enlarged blind spot without a fundus correlate to explain the field loss  White dots within the outer photoreceptor level, particularly the macular area  Old lesions manifest as tiny orange dots in the fovea  ¼-1/3rd DD  Macular granularity  Vitritis, periphlebitis  FA: early hyperfluorescence of punctate lesions in “wreath appearance”. Late staining of punctate lesions & leakage of ONH.  No known treatment  White spots disappear over days to weeks  Vision typically returns (1-10 weeks), but field defects may remain  No RPE residual irregularities

Multifocal Choroiditis  Pseudo-Histoplasmosis  Young myopic females 11  Blurred vision and blind spot enlargement  Multiple small white round lesions surrounded by pigment in posterior pole  Punctate inner choroidopathy  Presence of vitreous cells differentiates this from true Histoplasmosis  Prognosis good - Responds well to steroids

Clinical Pearl: There are posterior uveitic syndromes such as toxoplasmosis and some white dot syndromes that are visually recognizable. However, the majority of posterior uveitis syndromes present with signs and symptoms of posterior inflammation which do not necessarily identify the causative condition.