type of polymorphonuclear leukocyte, also contain abundant cytoplasmic granules and lysosomes, but the biochemical nature of eosinophilic granules consists of more basic protein (thus acidic dyes, such as eosin, will bind to these proteins).
Eosinophils have receptors for, and become activated by, many mediators; interleukin-5 (IL-5) is especially important.
Eosinophilic granule products such as major basic protein and ribonucleases destroy parasites efficiently; thus, these cells accumulate at sites of parasitic infection. Eosinophils are also important in allergic immune reactions.
Eosinophils are abundant in the conjunctiva and tears in many forms of atopic conjunctivitis, especially vernal and allergic conjunctivitis. They are not considered major effectors for intraocular inflammation, with the notable exception of helminthic infections of the eye, especially uveitis caused by toxocariasis.
LPS consists of 3 components: lipid A, O polysaccharide, and core oligosaccharide
The primary receptors are the toll-like receptors (TLRs), principally TLR4 and TLR2, which are expressed on macrophages, neutrophils, and dendritic cells, as well as on B cells and T cells. Lipid A is the most potent component, capable of activating effector cells at concentrations of a few picograms per milliliter.
effects of LPS are pleiotropic and include activation of monocytes and neutrophils, leading to upregulation of genes for various cytokines (IL-1, IL-6, tumor necrosis factor [TNF]); degranulation; alternative pathway complement activation; and direct impact on the vascular endothelium. LPS is the major cause of shock, fever, and other pathophysiologic responses to bacterial sepsis
The primary events are mediated largely by members of the selectin family and occur within minutes of stimulation (Fig 1-1). Nonactivated neutrophils express L-selectin, which mediates a weak bond to endothelial cells by binding to specific selectin ligands. Upon exposure to the triggering molecules described in the previous section, endothelial cells become activated, expressing in turn at least 2 other selectins (E and P) by which they can bind to the neutrophils and help stabilize the interaction by a process called adhesion. Subsequently, other factors, such as platelet-activating factor (PAF), various cytokines, and bacterial products, can induce upregulation of the β-integrin family. As integrins are expressed, the selectins are shed, and neutrophils then bind firmly to endothelial cells through the immunoglobulin superfamily molecules. Subsequent to adhesion, various chemotactic factors are required to induce transmigration of neutrophils across the endothelial barrier and extracellular matrix into the tissue site. Chemotactic factors are short-range signaling molecules that diffuse in a declining concentration gradient from the source of production within a tissue to the vessel. Neutrophils have receptors for these molecules and are induced to undergo membrane changes that cause migration in the direction of highest concentration. Numerous such factors have been identified: complement products, such as the anaphylatoxin C5a, fibrin split products
certain neuropeptides, such as substance P
bacteria-derived formyl tripeptides, such as N-formyl-methionyl-leucyl-phenylalanine (fMLP), leukotrienes
α-chemokines, such as IL-8
Activation of neutrophils into functional effector cells begins during adhesion and transmigration but is fully achieved upon interaction with specific signals within the injured or infected site. The most effective triggers of activation are bacteria and their toxins, especially LPS. Other innate or adaptive mechanisms (especially complement) and chemical mediators (such as leukotrienes and PAF) also contribute to neutrophil activation. Neutrophils, unlike monocytes or lymphocytes, do not leave a tissue to recirculate but remain and die.
Fibrin is the final deposition product of the coagulation pathway, and its deposition during inflammation promotes hemostasis, fibrosis, angiogenesis, and leukocyte adhesion. Fibrin is released from its circulating zymogen precursor, fibrinogen, upon cleavage by thrombin. In situ polymerization of smaller units gives rise to the characteristic fibrin plugs or clots. Fibrin dissolution is mediated by plasmin, which is activated from its zymogen precursor, plasminogen, by plasminogen activators such as tissue plasminogen activator. Thrombin, which is derived principally from platelet granules, is released after any vascular injury that causes platelet aggregation and release. (MHC) class I molecules (ie, HLA-A, -B, and -C) serve as the antigen-presenting platform for CD8+ T lymphocytes (Fig 2-2). CD8+ T lymphocytes include natural killer T cells and regulatory T cells. Class I molecules are present on almost all nucleated cells and generally function in the processing of peptide antigens that have been synthesized by the host cell itself
MHC class II molecules (ie, HLA-DR, -DP, and -DQ) serve as the antigen-presenting platform for CD4+, or helper, T lymphocytes (Fig 2-3). The antigen receptor on the helper T lymphocyte can recognize peptide antigens only if the antigens are presented with class II molecules simultaneously. However, only certain cell types express MHC class II molecules. Macrophages and dendritic cells are the most important of these types, though B lymphocytes can also function as class II-dependent APCs, especially within a lymph node
Five major classes of immunoglobulin (M, G, A, E, and D) exist, with 9 subclasses or isotypes (IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgE, and IgD). The basic immunoglobulin structure is composed of 4 covalently bonded glycoprotein chains that form a monomer of approximately 150,000-180,000 daltons Prodromal, acute uveitic, convalescent, and chronic recurrent. During the acute uveitic stage, diffuse, nonnecrotizing, granulomatous inflammation virtually identical to athat seen in SO with lymphs, macrophages, epithelioid and multinucleated giant cells with preservation of choriocapillaris, proteinaceous fluid exudates in subretinal space between detached neurosensory retina and RPE. Peripapillary choroid is primary site, ciliary and iris may be affected. Focal aggregates of epithelioid histiocytes admixed with RPE, or Dalen-Fuchs nodules appear between Bruchs and the RPE. Convalescent characterized by nongranulomatous inflammation with uveal infiltration of lymphs, plasma cells, and the absence of epithelioid histiocytes. Loss of choroidal melanocytes with decrease in melanin leading to SUNSET GLOW FUNDUS. Multiple atrophic depigmented lesions correspond to focal loss of RPE with chorioretinal adhesions. Recurrent stage is characterized by granulomatous choroiditis with damage to the choriocapillaris. abnormal serum creatinine level or decreased creatinine clearance
abnormal urinalysis findings, with increased β2-microglobulin level, proteinuria, presence of eosinophils, pyuria or hematuria, urinary white cell casts, and normoglycemic glycosuria
associated systemic illness, consisting of fever, weight loss, anorexia, fatigue, arthralgias, and myalgias; there may also be abnormal liver function, eosinophilia, and an elevated erythrocyte sedimentation rate
Surgical manipulation results in breakdown of the blood-aqueous barrier, leading to vulnerability in the early postoperative period. IOL implantation can activate complement cascades and promote neutrophil chemotaxis, leading to cellular deposits on the IOL, synechiae formation, capsular opacification, and anterior capsule phimosis. Retained lens material from extracapsular cataract extraction may exacerbate the usual transient postoperative inflammation. Iris chafing caused by the edges or loops of IOLs on either the anterior or the posterior surface of the iris can result in mechanical irritation and inflammation, although incidence of this type of complication using modern lenses is less than 1%. The motion of an iris-supported or anterior chamber IOL may cause intermittent corneal touch and lead to corneal endothelial damage or decompensation, low-grade anterior uveitis, peripheral anterior synechiae, recalcitrant glaucoma, and CME usually unilateral, and its symptoms vary from none to mild blurring and discomfort
diffuse iris stromal atrophy with variable pigment epithelial layer atrophy (Fig 6-13; B is affected eye)
small, white, stellate KPs scattered diffusely over the entire endothelium (Fig 6-14)
cells in the anterior chamber as well as in the anterior vitreous
glaucoma and cataracts, which occur frequently
macular edema, which is seldomly present
synechiae, fundus scars, and retinal periphlebitis, all of which are rare or absent
Note: Associations with ocular toxoplasmosis, herpes simplex virus infection, rubella, and CMV infection have been suggested.
made according to the distribution of KPs, presence of heterochromia, lack of synechiae, and lack of symptoms. Heterochromia may be subtle in a brown-eyed patient, and the clinician must look carefully for signs of iris stromal atrophy. Often, the inflammation is discovered during a routine examination, such as when a unilateral cataract develops. Usually, but not invariably, a lighter-colored iris indicates the involved eye. In blue-eyed persons, however, the affected eye may become darker as the stromal atrophy progresses and the darker iris pigment epithelium shows through. Marked by flulike symptoms, HA, nausea, meningismus, dysacusia, tinnitus, fever, orbital pain, photophobia, and hypersensitivity of skin and hair to touch several days before ocular symptoms. Focal neurologic signs like CNeuropathies, hemiparesis, aphasia, transverse myelitis, and ganglionitis may rarely occur. CSF may show lymphocytic pleocytosis with normal glucose for up to 8 weeks. Auditory problems frequently coincide with ocular symptoms. Sequential blurring of both eyes, 1-2 days after onset of CNS signs, bilateral granulomatous anterior uveitis, variable vitritis, thickening of posterior choroid with elevation of peripapillary retinal choroidal layer, hyperemia and edema of ON, and multiple serous RDs, often shallow in cloverleaf pattern around posterior pole, but may coalesce. May have profound visual loss. May seen MF KPs, iris nodules, elevated IOP, shallow AC from ciliary edema or annular choroidal detachment or low IOP from ciliary shutdown Anterior segment inflammation may be minimal or lacking; however, varying degrees of vitritis are commonly noted
characteristic multifocal, hypopigmented, ovoid, cream-colored lesions (50-1500 µm) at the level of the choroid and RPE in the postequatorial fundus; typically these lesions show a nasal and radial distribution, emanating from the optic nerve, and frequently they follow the underlying choroidal vessels
Lesions do not become pigmented
Retinal vasculitis, CME, and optic nerve head inflammation are important components of active disease. Late complications include optic atrophy, epiretinal membrane (ERM) formation, and, rarely, CNV.
uncommon condition presenting in otherwise healthy young adults, typically occurs with an influenza-like illness (50%) and affects men and women equally.
A genetic predisposition may be present, given the association of HLA-B7 and HLA-DR2
systemic conditions, which may have connection:
erythema nodosum, GPA, PAN, cerebral vasculitis, scleritis and episcleritis, sarcoidosis, and ulcerative colitis
Hep B vaccination, group A streptococcal and adenovirus type 5 infections, tuberculosis, Lyme disease, and mumps
minimal or no anterior segment inflammation; vitritis may be present but is usually mild.
Funduscopic findings include multiple large, flat, yellow-white placoid lesions at the level of the RPE that vary in size from 1 to 2 disc areas and are located throughout the posterior pole to the equator
New peripheral lesions may appear in a linear or radial array over the next 3 weeks. Papillitis may be observed, but CME is uncommon. Atypical findings include retinal vasculitis, retinal vascular occlusive disease, retinal neovascularization, and exudative retinal detachment. The lesions resolve over a period of 2-6 weeks, leaving a permanent, well-defined alteration in the RPE consisting of alternating areas of depigmentation and pigment clumping. Rapid evolution of the pigmentary changes, often over days, is a typical feature of the disease.
Marked by repeated bouts of granulomatous anterior uveitis, with development of KPs, posterior syn, iris nodules, iris depigmentation, and stromal atrophy. Posterior segment recurrences (vitritis, papillitis, multifocal choroiditis, and exudative retinal detachments) have been reported but are uncommon. AC recurrence may occur concomitantly with subclinical choroidal inflammation requiring systemic therapy. Visually debilitating sequelae of chronic inflammation develop during this stage and include PSC, glaucoma, CNV, and SRF Major criteria: recurrent oral aphthous ulcers, skin lesions (erythema nodosum, acneiform pustules, folliculitis), recurrent genital ulcers, ocular inflammatory disease; minor criteria: arthritis, GI ulceration, epididymitis, systemic vasculitis or associated complications, neuropsychiatric symptoms; types: complete (4 major), incomplete (3 major criteria or ocular involvement with 1 other major criterion), suspect (2 major criteria with no ocular involvement), possible (1 major). Note they often have positive pathergy test (sterile pustule at site of venipuncture). Note can also get GI ulcers. Neurologic involvement is most serious, mainly affects motor control from CNS vasculitis. Occur up to 70%, often recurrent and relapsing with often permanent and irreversible damage. Severe vision loss in 25%, more severe in men, 80% bilateral. Ocular involvement as presenting problem is relatively uncommon. Characterized by Non-granulomatous necrotizing obliterative vasculitis that can affect any or all portions of the uveal tract. Anterior uveitis may be only ocular manifestation, transient hypopyon in 25%, NG. Hypopyon may be small and can shift with head position. Anterior uveitis often resolves without treatment but often has explosive onset. Can get post syn, iris bombe, and ACG with relapses. Less common are cataract, episcleritis, scleritis, conjunctival ulcers, and corneal immune ring opacities IMT is ESSENTIAL. Those who have sight-threatening posterior segment ocular inflammation require prompt steroids AND IMT, which may include azathioprine, infliximab, cyclosporine, tacrolimbus, MMF, chlorambucil, or cyclophosphamide. Azathioprine often preferred first line, also helpful for ulcers and arthritis. Infliximab also helpful, but can lead to disseminated TB or CHF, therefore better for short term induction. Cyclosporine also a second line agent, less effective also nephrotoxic. Tacrolimus less toxic and may be used. Colchicine is helpful for mucocutaneous, ineffective for ocular BD. Chlorambucil can be effective at very low doses and may be good for durable remission. Cyclophosphamide may be used. IFN alfa-2a also useful. Acute, fulminant disease may arise without systemic prodrome years after prior infection with cutaneous or systemic infection with zoster, chickenpox, or herpetic encephalitis, 50s-70s. Associated iwth HLA-DQw7, Bw62, DR4, and HLA-Aw33, B44, and HLA-Aw33. Criteria include one or more foci of retinal necrosis with discrete borders, located in the periphery, rapid progression off antivirals, circumferential spread, occlusive vasculopathy with arteriolar involvement, prominent vitriitis, AC inflammation, optic neuropathy/atrophy, scleritis, pain supportive but not required; usually acute unilateral vision loss, photophobia, floaters, and pain. Fellow eye involved in 36%, often within 6 weeks, panuvieitis with KPs, post syn, elevated IOP, retinal lesion is yellow-white. Early on peripheral lesions are discontinuous and have scalloped edges that appear to arise in the outer retina, within days they coalesce to form a confluent 360 creamy retinitis that progresses in a posterior direction, leaving full thickness retinal necrosis, arteriolitis, phlebitis, and occasional heme in its wake, TRDs develop in 75%. Post pole tends to be spared, but exudative RD may arise. Often see disc swelling and rAPD. A classic or fulminant retinitis with large areas of heme against a background of whitened, edematous, or necrotic retina, in post pole, from disc to the arcades, in distribution of NFL and associated with vessels; a granular or indolent form found more often in periphery, characterized by little or no edema, heme, or sheathing, with active retinitis progressing from the borders of the lesion; and a perivascular form often described as a variant of frosted branch angiitis, an idiopathic retinal perivasculitis initially described in immunocompetent children Mild, self-limiting follicular conjunctivitis, usually seen early in course of disease; can also seen epithelial or stromal keratitis; episcleritis; bilateral, granulomatous iridocyclitis; dacryoadenitis; and less commonly CN palsies and Parinaud's; disc edema and optic neuritis, macular edema and heme, retinitis, punctate outer retinitis, choroiditis, MCP, pars planitis and vitritis, progressive subretinal fibrosis, uveitis, and secondary CNV. Most ocular disease is self limited. May require steroids, efficacy of systemic antivirals uncertain. Macrocephaly, hydrocephalus, and intracranial calcifications, neuro abnl, seizures, and mild MR, ocular findings include macular and chorioretinal peirpheral scarring, similar to that seen in congenital toxo, also optic atrophy, strabismus, and nystagmus. Differentiated from toxo by serologies and pattern of intracerebral calcifications, which tend to be diffuse in toxo compared to a periventricular distribution in congenital LCMV. Cataract, optic nerve head drusen, B/L diffuse pigmentary retinopathy involving both the posterior pole and periphery, normal or attenuated vessels, retinal edema, and macular star. ERG and acuity typically normal. But most common are keratitis and a mild, papillary, nonpurulent conjunctivitis, often resolve without sequelae, rare in US, but worldwide a measles corneal complciation leading to blindness is common. Can treat symptomatically with topical antivirals or antibiotics to prevent secondary infections in patients with keratitis Rare late complication of acquired measles, esp when acquired young, but presents in late childhood/adolescence. Note visual impairment, behavioral disturbances, memory impairment, myoclonus, spastic paresis, dementia, and then death in a few years. Ocular findings may precede neuro and include maculopathy with focal retinitis and RPE changes, progresses to involve posterior pole and peripheral retina; disc swelling, papilledema, optic atrophy, macular edema, macular pigment epithelial disturbances, intraretinal heme, gliotic scar, whithish retinal infiltrates, serous macular detachment, drusen, preretinal membrane, macular hole, cortical blindness, hemianopsia, horizontal nystagmus, and ptosis. Little if any vitritis. Mottling and scarring of RPE as retinitis resolves. Compared to MS, CME and retinal vasculitis are prominent features of MS but not seen in patients with SSPE. Treatment consists of combo of oral Isoprinosine and intraventricular IFN alpha and require lifelong therapy if works Pain, photophobia, conj hyperemia, and blurred vision; characteristic multifocal chorioretinitis is seen in most with NGAU and vitreous cell, lesions in midperiphery in linear arrays following course of RNFL w/ or w/o involvement of post pole. Active lesions are whitish to yellow, flat and deep, and evolve with pigmentation and atrophy. FA reveals central hypofluorescence with late staining when active and early hyperfluorescence with late staining of inactive lesions due to blockage from pigment and peripheral hyperfluorescence from atrophy. ICG reveals more hypofluorescent spots than on FA/DFE. Other findings include ant uveitis, vitritis, heme, disc edema, atrophy, and less commonly focal retinal vascular sheathing, occlusion, CNVI palsy, and nystagmus. Most often self limited, but persistent loss from CNV, scars, ischemic maculopathy, vi theme, TRD, ON pathology, and retrogeniculate damage Acute febrile illness acquired through direct contact with blood or organs of infected animals or inhalation of aerosols during slaughter or from bites of mosquitos. Can be uncomplicated, hemorrhagic fever, or neuro involvement with encephalitis. Ocuar involvement with bilateral macular or paramacular retinitis as well as heme, vitritis, ON edema, vasculitis, and ant uveitis often observed. FA reveals delayed filling of retinal and choroidal circulation with early hypofluorescence and late staining of the inflammatory lesions. Spontaneous resolution of retinitis, retinal heme, and vitritis observed, leaving optic atrophy, ischemic retina, and attenuated occluded vessels. Long term vision loss from scars or optic atrophy. Topical steroids may help ant uveitis, but systemic antivirals and anti-inflammatories with unknown benefit Retrovirus endemic in Japan, Carribean, and parts of Central and South America by blood, sex and breast feeding. May cause a uveitis in carriers, other ocular manifestations include retinal infiltrates from T-cell leukemia/lymphoma, retinal degeneration, optic neuropathy, and keratopathy as well as KCS. Most are an INTERMEDIATE UVEITIS, blurry vision and floaters with a mild granulomatous ant uveitis, unilateral vitritis, membranous vitreous opacities, or snowballs, retinal vasculitis, exudative lesions, disc abnormalities, and CME also seen. The vasculitis responds very well to steroids and should be included on ddx of retinal vasculitis. ICG suggests choroidal involvement. The keratitis does not affect vision and most likely asymptomatic lymphoplasmacytic infiltrates. Many cases of HTLV uveitis respond to topical, periocular, or systemic steroids Those pathologies with CNV besides AMD: angioid streaks, choroidal rupture, idiopathic CNV, MCP, PIC, granulomatous fundus lesions mimicking the scarring in OHS (toxo, TB, coccidiodomycosis, syphilis, sarcoid, and toxocariasis). Atrophic spots and maculopathy of myopic degeneration and disciform scarring in AMD may be confused Unilateral blurred or hazy vision, floaters; mild to moderate anterior uveitis, up to 20% have acutely elevated IOP at presentation. Classically appears as focal, white retinitis with overlying moderate vitritis, often adjacent to a pigmented chorioretinal scar. More often in posterior pole but occasionally near disc and mistaken for papillitis. Vessels in the vicinity of activity may show perivasculitis with diffuse venous sheathing and segmental arterial sheathing (Kyrieleis arteriolitis). Other complications include cataract, CME, serous RD, and CNV. Focal retinitis in absence of chorioretinal scarring should raise suspicion of acquired disease or another cause for necrotizing retinitis. When old or immunocompromised, may be atypical with large, multiple, and/or B/L with or without chorioretinal scars and punctate outer retinal toxoplasmosis characterized by small, multifocal lesions at the level of the deep retina with scant overlying vitreous inflammation.