Posterior Uveitis PDF

Posterior Uveitis: along with choroidal inflammation, we can see inflammation involving adjacent structures such as the retina, vitreous, optic nerve head, retinal vessels, sclera Can have anterior uveitis: spill over reaction (especially retinitis) or panuveitis Symptoms: o #1 C...

Posterior Uveitis: along with choroidal inflammation, we can see inflammation involving adjacent structures such as the retina, vitreous, optic nerve head, retinal vessels, sclera Can have anterior uveitis: spill over reaction (especially retinitis) or panuveitis Symptoms: o #1 CC: Blurred vision with no pain o May present w/ a little redness but not too much o May report floaters o Pain and photophobia seen in anterior uveitis is not likely to occur § Minimal anterior segment inflammation (if any) o External eye is typically white depending upon etiology o Anterior uveitis § Typically asymptomatic spill-over from posterior chamber Vasculitis: can be either periphlebitis (white sheet surrounding the veins) OR periarteritis (white sheet surrounding the arteries) o Periphlebitis: Sarcoidosis, Toxoplasmosis, CMV, Syphilis, Lyme o Periarteritis: Acute retinal necrosis (ARN), Bechet, syphilis, Toxo also o Or both: angiitis (arteries and veins affected) o In vasculitis: we can see “candle wax” dripping along arteries &/or veins § § Panuveitis: inflammation of the A/C, vitreous, retina, and choroid It could be: o Focal: single lesion, may be localized like in Toxoplasma or Candida § We can see plaques or spots § Plaques: ~1 disc diameter § Spot: 100-200 microns (0.1 mm-0.2 mm)  o Multifocal: multiple lesions like in MEWDS, Histoplasmosis, ARN, CMV, Syphilis, Tuberculosis § We can see plaques or spots o Diffuse: all over, like in CMV retinitis Retinitis: superficial, inflammation of the retina. o Fluffy, white retina with diffused borders and a LOT of vitritis o Seen in Toxoplasmosis- focal, Candida- focal, herpetic uveitis- multifocal to diffuse in ARN & CMV, RP, Syphilis- multifocal or can be anything Choroiditis: deeper, inflammation of the choroid o Yellow or grey retina w/ demarcated borders w/ NO vitiritis o Focal § TB* § Candida- retinochoroiditis and chorioretinitis § Toxocara- chorioretinitis o Multifocal § Histoplasmosis- the purest § Syphilis- can be anything § Lyme disease- cousin of syphilis o Serpiginous choroiditis Retinochoroiditis: more inflammation of the retina and then choroid o “dirty” lesion, retinitis w/ deeper yellowish lesions o Congenital toxoplasmosis and Birdshot retinochoroiditis o “Old”/inactive retinochoroiditis: punched out lesions different size and shape = SCARS! Chorioretinitis: more inflammation of the choroid then retina o Similar to choroiditis but has a little vitritis o Seen in Candida, Toxocara, Syphilis and in males- SC, ARPE o Vitritis and anterior uveitis, but deep lesions o Can have CME and then VA goes down o May have some cells and flare (some haziness, some fluffiness, some yellow present) o Birdshot chorioretinitis: multifocal -> plaques -> woman in their 50s -> order HLA-A29* and BINGO Neuroretinitis: anterior optic nerve and peripapillary retina is inflamed o Most common causes of neuroretinitis § Toxoplasmosis***,Syphilis, TB, Sarcoidosis, Cat-scratch disease- Bartonella, Lyme disease, Idiopathic: Leber stellate neuroretinitis, histoplasmosis o Look at website for infectious vs inflammatory causes of neuroretinitis o Usually involves the retina and macula o Nerve is inflamed and macula stars can appear o Henle’s layer terminates in OPL and is obliquely oriented  o o Vasculitis: vessels are inflamed and whitish material along the vessels o Veins and arteries? *don’t forget to look at all pictures and OCTs* ERG/ mfERG Mass electrical response of the retina Overall rod-and-cone generated retinal responses Generalized retinal dysfunction  mfERG is a calculated visual field map of cone responses and has local retinal function. o Similar to 24-2 HVF area o Ancillary testing Aqueous and vitreous paracentesis for PCR FA, ICGA Ultrasound Chorioretinal biopsy Lab tests in Uveitis CBC, CMP ESR, CRP ANA, RF ACE ELISA, IgG and IgM titers for infectious organisms Sabin-Feldman dye test HLA typing (HLA-B27, B29, B5, etc.) PPD, Interferon-y release assays (IGRA) ANCA (c/p) VDRL, RPR, FTA-ABS Chest x-ray: o Lumbosacral spine films o Gallium scan o Urinalysis, urethral cultures Infectious Uveitis Toxoplasmosis (the most common cause of infectious post. uveitis) o Caused by obligate intracellular protozoan toxoplasma gondii § The known definitive hosts for T. gondii are members of family Felidae (domestic cats and their relatives) § Intermediate hosts include mice, livestock and humans o T. gondii can infect humans via these routes  § Pregnancy § Eating meat or vegetables contaminated w/ cat feces § Human infection occurs most often through eating undercooked meat that contains cysts o Tachyzoites are the active form of the parasite; they can be carried in the bloodstream, disseminate to different organs, and invade cells § Found mainly within intestine epithelial cells Once inside a cell, they turn into bradyzoites and create tissue cysts, mainly in muscle, liver, and brain o OITS Summary: § 1) Sporozoite (cat): produced by sexual activity inside the oocyte § 2) Tachyzoite: proliferative form in humans § 3) Bradyzoite: encysted and dormant § 4) Bradyzoite: sits in the NFL § 5) Bradyzoite: near old scars, and viable for 25 years § 6) Immunosuppression can reactivate bradyzoite § 7) May spontaneously reactivate without immunosuppression o 4 clinical disorders: § Congenital toxoplasmosis Most infected newborns are delivered asymptomatic at birth The most common clinical manifestation of congenital toxoplasmosis is retinochoroiditis* Bilateral involvement varies between 22-40% & is more frequently observed (65-97%) in patients w/ congenital toxoplasmosis In severe cases, can present w/ hydrocephaly, microcephaly, cerebral calcifications, convulsions, psychomotor retardation, hepatosplenomegaly, jaundice, lymphadenopathy, rash, fever, and abnormal cerebrospinal fluid findings § Acquired systemic toxoplasmosis Subclinical is the most frequent Flu-like syndrome, which is uncommon and self-limiting Only 10-20% of Toxoplasma infections in the adult are symptomatic HLA-Bw62 linked (not required to remember) IgM: when activated, is + IgG: takes more time to develop When inactive, IgM is (-) and IgG (+) Active: IgM and IgG are positive § Toxoplasmosis in the immunocompromised host (acquired or reactivation of a latent infection) More life-threatening Fever, encephalitis, myocarditis, and pneumonitis  >50% have central nervous system involvement § Reactivation of ocular toxoplasmosis following either congenital or acquired systemic disease Would look like white next to scars and hazy vitreous Active vitritis w/ headlights in a fog appearance adjacent to an area of old scarring Hazy vitreous next to scars = reactivation If infection is inactive or chronic, the vitreous is CLEAR o o Unilateral focal localized retinitis and the most common cause of infectious posterior uveitis o When encountering active toxoplasmosis in young patients, strongly consider HIV testing o Ocular signs § Unilateral, necrotizing focal retinitis with secondary choroiditis § A lot of vitritis All white in primary White fluffy next of scar (w/ black) if reactivation o ** if you see fluffy w/ scar = reactivation In posterior pole most often seen § Retinochoroiditis** § Cyst in retina even if no lesions (patient had systemic in the past) § Headlight in a fog: more over the lesion & active vitritis § Spill over: reaction from posterior uveitis from the anterior segment w/ cells and flare § High IOPs (one of the reasons of uveitis w/ high IOP*) #1: Herpetic uveitis #2: Fuch’s § ONH edema-papillitis  § Neuroretinitis** § Vasculitis- periphlebitis; periarteritis can also be seen o Complications § CME § ERM § CNVM § Serous or tractional retinal detachment o Symptoms § Sudden onset of blurred vision, floaters § Visual loss § Photophobia because A/C reaction § Usually white eye but can be red! o o PEARL in regard to reactivation § The key diagnostic sign of toxoplasmosis is an active V… with a “ “ adjacent to an area of ____ o Ocular Toxoplasmosis: Neuroretinitis o Approach & diagnosis § Clinical signs § Differential Dx TB Syphilis Sarcoidosis Toxocara § Serum IgG, IgM § Dye test (Sabin-Feldman): the titer is considered positive when more than 50% of the parasites remain unstained  § PCR § HLA: HLA-Bw62 o Treatment § Combination of anti-microbials and steroids in majority of cases § No final consensus since different trends § Goal is to prevent retinal damage, ONH and sequela of inflammation § Pyrimethamine 200 mg orally on day 1, followed by 50 mg orally daily for 4 weeks Pyrimethamine (Daraprim) interrupts parasitic metabolic activity § Sulfadiazine 2 g orally as a loading dose followed by 1 g orally four times daily for 4 weeks § Folinic acid 15 mg orally every other day twice a week § If allergic to sulfa: Azithromycin, Clindamycin, Atovaquone, Trovafloxacin, Minocycline § Vision threatening lesions: Corticosteroids to be used only when vision is threatened: Prednisone 1 mg to 1.5 mg/kg/day, gradually tapered over a period of 4 weeks Periocular injection of triamcinolone acetate 40 mg if intolerance, compliance, economical reasons 3 days after initiation of antimicrobial agents § Alternate treatment options: Bactrim DS (Trimethoprim/Sulfamethoxazole) BID Azithromycin Clindamycin (alternate to sulfadiazine*, used w/ pyrimethamine) Atovaquone: similar alternative Clindamycin Trovafloxacin w/ pyrimethamine CBC weekly if on pyrimethamine Clindamycin (Lacosamide), and Fluoroquinolone Trovafloxacin act synergistically w/ pyrimethamine Candida o Associated w/ catheters, IV drug abuse, total parenteral nutrition and chronic lung disease such as cystic fibrosis o Unilateral focal localized retinitis w/ some vitritis, one or several creamy white chorioretinal lesions w/ overlying vitritis o Presence of floating cotton ball colonies or string of pearls in the vitreous o Treatment: § No vitreal involvement: Fluconazole PO 100-200 mg qd, resistant cases use Voriconazole PO IV, or intravitreal § Vitreous involvement: Vitrectomy and intravitreous Amphotericin B  o Toxocara o Caused by roundworm of intestine of dogs and cat called toxocara canis o Human infected by ingesting soil contaminated with the eggs o Symptoms range ~12 mo. and may not be observed until they fail a school vision screening test o Unilateral, focal, granumola (teenagers), diffuse endophthalmitis (kids) § Posterior pole granuloma due to ocular toxocariasis with prominent retinal folds (a), epiretinal membrane formation (b),and a traction band extending from the lesion to the optic disc and retinochoroidal anastomosis (c) The causes of vision loss may be by direct involvement of the macula or optic disc, by the secondary formation of retinal folds or epiretinal membranes, or rarely by the development of choroidal neovascularization § Ocular toxocariasis with peripheral granuloma and vitreoretinal traction o Pathogenesis of toxocara § Ocular toxocariasis is caused by the migration of Toxocara larvae into the posterior segment of the eye  § The most common one is via the brain to the cerebrospinal fluid and then to the choroid § Other possible pathways are via the brain to the optic nerve or via the arteries from the internal carotid artery to the ophthalmic artery, retinal central artery, or ciliary artery § Migrated larvae secrete enzymes, waste products, and cuticular components, which cause tissue damage, necrosis, and marked inflammatory reaction, with eosinophils as the most component § These eosinophils release toxic proteins which contribute to the pathology and symptomatology of toxocariasis § The typical pathological finding in ocular toxocariasis is eosinophilic granulomas with central necrosis and remnants of Toxocara larva surrounded by a mixed inflammatory infiltrate with numerous eosinophils § Ocular toxocariasis is usually due to a single Toxocara larva invading the eye. This results in a low-level immune response which is insufficiently activated to kill the larva and allows its persistence in the eye for years. During this long period, it can migrate through ocular tissues causing mechanical and immunopathological damage § The pathogenesis of ocular toxocariasis in the human depends on the inflammatory reactions activated by the existence of larva in the eye, the host immune response, the number of the larvae present in the eye, the incidence of reinfection, and the host sensitization to the secreted or excreted products by the larvae o Diagnosis: § Because Toxocara larva does not develop into the adult stage in humans, the parasitological examination of fecal samples is not beneficial for the laboratory diagnosis. § Eosinophils detected in the aqueous or vitreous fluid are more direct indicators of ocular infection, but such fluids are rarely available for testing § The diagnosis of ocular toxocariasis can be carried out by the conjunction of patients’ history (contact with dogs or cats, geophagia, eating of undercooked or raw meats), distinguishing the typical manifestations by ophthalmic examination and immunodiagnostic methods to reveal the specific antibodies in serum and ocular fluids. In addition, molecular diagnosis, medical imaging techniques, and histopathologic observation of Toxocara larva in the surgically obtained specimens can be performed o Ocular manifestations: § Clinical manifestations and severity of ocular toxocariasis rely on the primary anatomical site implicated, the number of the larvae existing in the eye, and the immune reaction of the host § Photophobia  § Floaters § Leukocoria*** § Strabismus § White pupillary reflex § Bloodshot conjunctiva § Mild ocular pain § Vitreous inflammation § Blindness of one eye which is recorded in about 80% of cases and is permanent in the most patients § Endophthalmitis is a panuveitis manifesting as a red, painful eye with diffused intraocular inflammation and no apparent nodular lesion. § It’s observed in 25% of cases, between 2 and 8 years old, presenting with leukocoria, strabismus, and hypopyon. In the fundus, there are granulomatous vitritis, cyclitic membranes, and retinal detachment o Signs: § Occasionally, the retinal symptoms may be associated with those due to involvement of the central nervous system § Ocular toxocariasis may present as an acute inflammation in the peripheral retina and ciliary body. § About 20–40% of the infected eyes with toxocariasis manifest as a peripheral granuloma. § It is observed in cases with ages between 6 and40 years old. The peripheral granuloma presents as a hazy, white, elevated mass in the peripheral fundus. § It can be associated with retinal folds that may extend from the peripheral mass to the optic nerve head or to other areas of the fundus. § In some cases, the traction may lead to heterotopia of the macula (Fig. 2) (Cortez et al. 2011). Reduced vision in patients with peripheral ocular toxocariasis is due to macular involvement by posteriorly extending falciform folds or exudate. § Amblyopia may develop in young patients with media opacities and/or macular involvement o Types: § Visceral larva migrans Severe systemic infection which usually occurs in young patients § Ocular toxocariasis Patients are otherwise healthy, have hx of pica, the age of presentation is older § Diffuse endophthalmitis Between the ages 2-9 w/ leukocoria, strabismus, or unilateral visual loss Anterior uveitis of granulomatous type  Hypopyon Vitritis Dense yellow vitreous mass Peripheral granuloma Secondary retinal detachment can happen § Posterior pole granuloma Unilateral visual impairment between the ages of 6-14 y/o Absence of intraocular inflammation Round yellow white, solid granuloma Vitreoretinal traction bands and localized tractional retinal detachment § Peripheral granuloma Unilateral White peripheral granuloma in any quadrant of the fundus Can resemble pars planitis in young o Approach: testing § The best choice serodiagnostic methods are ELISA-IgG as a screening test and confirm the positive samples by western blot test § Detection of specific Toxocara antibodies in aqueous and/or vitreous samples using different immunological methods assists the confirmation of ocular toxocariasis diagnosis and distinguishes it from retinoblastoma § The definitive diagnosis of ocular toxocariasis is via the histopathological identification of Toxocara larva or its fragments in the vitrectomy specimens o Treatment: § Treatment is usually based on the intensity of symptoms, the appearance of intraocular inflammation, the visual impairment, the macular involvement, and the occurrence of ocular damage § Corticosteroids are the mainstay medical treatment for ocular toxocariasis as they have the ability to decrease the release of local mediators of inflammation leading to the suppression of inflammation, induce cell membranes stabilization, and prevent vitreous opacification and tractional retinal detachment § Oral prednisolone is the most commonly used anti-inflammatory drug with an effective dosage of 1 mg/kg/day for a period of 1 month or more when needed; after that, the dose is reduced § Usage of the anthelmintic treatment for patients with ocular toxocariasis may induce an intraocular inflammation due to a hypersensitivity reaction to larval death inside the eye, leading to the permanent damage of the eye- Anthelmintic treatment can be given, especially with the presence of extraocular toxocariasis symptoms.  § Albendazole and diethylcarbamazine, the most commonly used drugs, have larvicidal activity and are able to penetrate the blood- brain barrier. Other anthelmintic drugs such as thiabendazole, mebendazole, and tinidazole are highly effective in preventing the progression of Toxocara larvae to the neurotropic phase of infection § Pars plana vitrectomy is the most common procedure in ocular toxocariasis, especially for patients who do not respond to the medical treatment or have severe complications § Inactive: no treatment § Active: Benzimidazole derivative w/ local/systemic steroid Histoplasmosis o Purest form of choroiditis****** because there are absolutely no vitreous cells o Can be confused w/ MCP o Choroidopathy caused by the fungus Histoplasma capsulatum o Most common in the southeastern, middle Atlantic, and central US (areas bordering Ohio River Valley and Mississippi River Valley) § Indiana, Ohio, Illinois, Kentucky, Tennessee, and Mississippi, Maryland, West Virginia o People living in the Ohio & Mississippi River Valleys are known to have as high as a 70% rate of positive skin test for exposure to H. Capsulatum o Associated w/ birds and bats (found in bats feces) o Affects ages 20-50. Rare in patients of African descent. o Neuroretinitis can occur when active infection before the POHS o Inhaled fungus… spores o Inhaled mycelial spores of H. Capsulatum o Into choroid… granulomatous § These spores undergo transformation to the yeast phase o Presumed Ocular Histoplasmosis Syndrome (POHS) § Represents an immune-mediated response in individuals previously exposed to the fungus § Patients w/ POHS show an increased prevalence of HLA-B7********* & HLA-DR2 § POHS is asymptomatic unless it causes a CNVM (choroidal vasculature formation) § Only ~4.4% of patients w/ a positive skin test have evidence of POHS § Therefore, the relationship b/w H. Capsulatum & POHS remained presumed § Treatment: Routine F/U when inactive Home Amsler to monitor for neovascularization Oral steroids when active Antifungal only used if concomitant systemic  CNVM involvement: anti-VEGF injections through pars plana o Flu-like illness, retinal lesions reactivate 10-30 years later. The classic triad is: § Peripapillary atrophy § Punched out chorioretinal lesions, 200 um in diameter in PP and mid- periphery § Macular CNVM- late manifestation, causes blindness § NO VITRITIS!! § Equatorial streaks = proposed to be the 4th sign & noticed in 5% of cases o o Exudative maculopathy § Choroidal neovascularization (CNV) is a late manifestation which usually develops b/w the ages of 20 and 45 years in about 5% of eyes Herpetic uveitis: (Zoster is more common in older; Simplex common in young) o ARN (Acute Retinal Necrosis) § Due to HSV and VZV § ARN usually occurs in immunocompetent or immunosuppressed, younger than 25 y/o § Fulminant retinitis w/ moderate to severe uveitis (full thickness retina) Angry red eye, acute anterior uveitis, retinitis § ARN classically consists of anterior uveitis and peripheral necrotizing retinitis often w/ secondary retinal vasculitis and optic nerve inflammation § ARN Diffuse retinitis § Symptoms Progressive visual blurring in one or both eyes occurring over several weeks Ocular pain**** Redness**** Floaters**** § Signs Prominent AU (granulomatous or non-granulomatous) Significant vitreous cellular infiltration One or more foci of retinal necrosis (whiteness) w/ discrete borders, located in the peripheral retina o Diffuse retinitis** Rapid progression of the disease in the absence of therapy Eventually, most untreated eyes can be expected to develop RD resulting from the development of multiple full-thickness retinal breaks accompanied by traction/exudation § PEARL In any patient w/ anterior uveitis, a careful DFE is mandatory not to miss the diagnosis of ARN syndrome Moderate or severe vitritis is a prominent feature of ARN (in contrast to CMV retinitis)*** § If BILATERAL ARN (aka BARN) Circumferential spread of the disease Evidence of occlusive vasculopathy and arteriolar involvement (periarteritis: vasculitis**) o May have scleritis  ONH disease: hyperemia or true neuropathy § Associated w/ HLA-DQw7, HLA-Bw62, and DR4 § No predilection for sex, race, or age has been identified. ARN has been reported in patients ranging from 9-89 y/o § HSV causes ARN in patients younger than 25 years § Hx of recent zoster or varicella inf. In some cases § PCR may yield a + result from the aqueous or vitreous fluid § ARN § § Treatment Acyclovir IV: initial dosage of 15 mg/kg 3 times daily for 10 days, followed by oral Acyclovir 800 mg 5 times/day for at least 6 weeks, tapered gradually over the next 6 months In patient not responding to Acyclovir, oral Famciclovir or Ganciclovir have been recommended. Intraocular injections too. Others that can be used include Valaciclovir and Foscarnet.  Oral corticosteroids (controversial) are used to control active inflammation Prophylactic laserpexy Frequent DFE during the convalescent period and for several years thereafter § “Folder” for ARN #1: Retinitis #2: Angry AU #3: Diffuse retinitis #4: Periarteritis #5: HZV but o HSV in patient younger than 25 y/o #6: could have high IOP o CMV (Cytomegalovirus retinitis) § AIDS; immunosuppressed; CD4 < 50mm3; organ transplant § Member of the Herpesviridae family § Signs: Necrotizing retinitis granular whitening located deeper in the retina = diffuse* & periphlebitis Vitreous relatively quiet but significant vitritis can occur AU = Stellate KP’s & high IOP Stellate keratic precipitates w/ cell and flare on the cornea and in A/C o PEARL! KP in a stellate pattern can be from Herpes, Fuch’s heterochromic iridocyclitis, CMV High IOP o PEARL! HSV & HZV, Toxoplasmosis, CMV, Possern- Schlossman (glaucomatocyclitic crisis) Necrotizing retinitis o Granular borders o Brushfire appearance o Posterior lesions o Retinal edema  o Retinal hemorrhages o Crumpled cheese and ketchup o Peripheral lesions o Less hemorrhagic o Granular o Does not follow a vascular arcade o