BMS 200 Eye Pathologies PDF

Eye part 3 – Eye Pathologies BMS 200 Cataracts = Any opacity of the lens ▪ Worldwide, most common reversible cause of blindness Location of the opacity determines the appearance of the cataract ▪ Cortical – radial or spoke-like opacity, found in the anterior or po...

Eye part 3 – Eye Pathologies BMS 200 Cataracts = Any opacity of the lens ▪ Worldwide, most common reversible cause of blindness Location of the opacity determines the appearance of the cataract ▪ Cortical – radial or spoke-like opacity, found in the anterior or posterior cortex of the lens ▪ Nuclear sclerosis – yellow-brown discolouration of the central lens ▪ Posterior subcapsular – next to the capsule, in the posterior aspect of the lens Cataracts Cataracts 90% of cataracts are caused by changes within the lens brought about by aging ▪ Typically results in nuclear sclerosis, the yellow-brown cataract gives everything a yellow tinge and reduces the amount of blue light that is transmitted ▪ The lens cortex can liquefy, resulting in a cortical cataract Systemic diseases and medications can also contribute to cataract formation ▪ Diabetes mellitus, Wilson’s disease, hypocalcemia, systemic steroid use Diseases that affect the eye locally (trauma, radiation, uveitis) can also cause cataracts Cataracts – clinical features Gradual, painless, progressive decrease in VA ▪ Glare, dimness, halos around lights at night, monocular diplopia ▪ “second sight” phenomenon: patient is more myopic than previously noted, due to increased refractive power of the lens (in nuclear sclerosis only Visible opacities on ophthalmoscopic examination Most types of cataracts are amenable to surgery or laser therapy – prognosis is fairly good ▪ A proportion are at risk of posterior subcapsular cataracts post-surgery Major forms of cataracts Uveitis Inflammation of the choroid layer: ▪ Iris (iriditis) ▪ Iris+ciliary body (iridocyclitis) ▪ Posterior compartment (posterior uveitis) ▪ Endopthalmitis – really bad, rare, often bacterial infection of entire eye In general, divided into anterior and posterior uveitis Not very common – about 8 cases/100,000/year… 90% are an anterior uveitis ▪ Can cause a lot of different complications: Macular edema and destruction Glaucoma Corneal damage Cataracts Destruction of the entire eye Uveitis Primary Site of Type Includes Inflammation Iritis/iridocyclitis/anterior Anterior uveitis (90%) Anterior chamber cyclitis Pars planitis/posterior Intermediate uveitis Vitreous cyclitis/hyalitis Focal, multifocal, or diffuse choroiditis/chorioretinitis/ Posterior uveitis Choroid retinochoroiditis/retinitis/ Neuroretinitis Anterior chamber, Panuveitis vitreous, and/or choroid Uveitis Etiology: ▪ For anterior (about 90%): idiopathic, seronegative spondyloarthropathies/IBD, sarcoidosis, JIA, lupus, Behcet’s disease, AIDS, herpes Most common are idiopathic, sarcoidosis, and autoimmune ▪ For posterior: a lot of infections: Toxoplasmosis and CMV infections are common causes Autoimmune/sarcoidosis causes can also cause posterior Uveitis - history Anterior uveitis: ▪ Acute – Pain, redness, photophobia, excessive tearing, and decreased vision; pain generally develops over a few hours or days except in cases of trauma ▪ Chronic - Primarily blurred vision, mild redness; little pain or photophobia except when having an acute episode Posterior uveitis: ▪ Blurred vision, floaters ▪ Symptoms of anterior uveitis (pain, redness, and photophobia) absent Symptoms of posterior uveitis and pain suggest anterior chamber involvement, bacterial endophthalmitis, or scleritis Uveitis - Physical Conjunctival injection – the limbus is usually more inflamed than the periphery ▪ In conjunctivitis, the periphery is still fairly erythematous compared to the limbus Reduced visual acuity Funny-looking iris and pupil with anterior uveitis: ▪ Stuck to the lens (development of synechiae) ▪ Blood or pus ▪ Flare (white cells in the anterior chamber) ▪ Increased intraocular pressure (need a tonometer to measure…)  Hypopyon and hyphema  Production of aqueous humour - review See 3-step process with image If drainage of aqueous humour is impaired, can result in massively increased intra-ocular pressures ▪ “pushes back” on the retina behind and can damage it ▪ Drainage for aqueous humour other than through the scleral venous sinus is very limited  Production of aqueous humour - review The scleral venous sinus is found on the deep surface of the junction between the cornea and the sclera (aka limbus) The endothelium of the cornea is replaced by a complex filter, known as the trabecular meshwork, which lies over the scleral venous sinus ▪ Composed mostly of fibroblasts and ECM The iris can “flop over” the scleral venous sinus and block it The angle between the the iris and the lens can also become blocked Glaucoma = Progressive, pressure-sensitive, optic neuropathy involving characteristic structural changes to optic nerve head + associated visual field changes Most glaucomas are associated with elevated intraocular pressure, although some patients with normal intraocular pressure may develop characteristic optic nerve and visual field changes (normal or low- tension glaucoma) ▪ Normal IOP = 10 – 21 mm Hg One of the leading causes of blindness, only half of those who have it know they have it ▪ 1.6 million in US have visual impairment due to glaucoma Glaucoma Glaucoma may be classified into two major categories – open-angle and closed-angle (angle closure) Refers to the angle between the cornea and the anterior iris Open angle glaucoma = aqueous humor has complete physical access to the trabecular meshwork ▪ Elevation in intraocular pressure results from an increased resistance to aqueous outflow in the open angle ▪ Primary open-angle glaucoma is the most common (95% of all glaucoma cases) – estimated 2.5 million of those > 40 years have it in the US, many are unaware Closed-angle glaucoma = peripheral zone of the iris adheres to the trabecular meshwork and physically impedes drainage of aqueous from the eye Primary Open-Angle Glaucoma Most common form Possible causes: ▪ Obstruction of the trabecular meshwork by “stuff” ▪ A loss of trabecular endothelial cells, or reduction of the size of their pores ▪ A loss of normal phagocytic activity ▪ Disturbance of neurologic feedback mechanisms Many have relatively normal IOP – however, increased IOP (40% risk of glaucoma if IOP is between 30 – 40 mmHg) is the major risk factor for progression Primary Open-Angle Glaucoma Clinical manifestations: ▪ Asymptomatic, bilateral (but one side usually worse than the other) insidious loss of vision Insidious because it’s slow, and it tends to affect temporal fields first ▪ Physical exam shows increased IOP, flame-shaped hemorrhages, and increased cup-disk ratio as well as optic nerve atrophy  Secondary Open-Angle Glaucoma Can be caused by trabecular meshwork clogging: ▪ High-molecular-weight lens proteins from phacolysis ▪ Red cells after trauma (ghost cell glaucoma) ▪ Iris epithelial pigment granules (pigmentary glaucoma) ▪ Necrotic tumors (melanomalytic glaucoma) Can develop quickly, and have a similar, symptomatic presentation to acute angle- closure glaucoma Primary Angle-Closure Glaucoma 5% of all glaucoma Risk factors include: ▪ Race (Asian, Southeast Asian, Inuit at high risk) ▪ Hyperopia, female sex ▪ Situational, drugs – antihistamines, dim lighting (i.e. movie theatre) Transient apposition of the pupillary margin of the iris to the anterior surface of the lens ! obstruction of aqueous humour flow (pupillary block) ! continued production elevates anterior chamber pressure ! increased posterior chamber pressure ▪ Marked elevation in intra-ocular pressure – usually exceeds 40 mm Hg ▪ Can damage the lens as well as the retina Primary Angle-Closure Glaucoma Clinical Features ▪ Usually very painful, photophobic, unilateral red eye – redness includes peripheral conjunctiva and also encroaches upon the limbus ▪ Pupil is usually fixed in mid-dilation, decreased visual acuity, haloes around lights seen ▪ Other features – subcapsular opacities in the lens, sustained high pressures can cause corneal edema and degeneration RED FLAG – vision loss (irreversible) in hours - days Secondary Angle-Closure glaucoma Typically associated with diabetes ▪ Neovascular membrane develops over the trabecular meshwork ▪ Pulls the iris closer to the trabecular meshwork, also leads to blockage of flow Uveitis (anterior) can cause the development of synechiae (constricting membranes) that adhere the iris to the lens and close the angle Glaucoma - Treatment Acute closed-angle – laser iridotomy, sometimes cataract surgery in those with “thick” lenses ▪ Meds - until surgery can be performed, medications can reduce the production of aqueous humour (all meds FYI) Topical alpha 2-adrenergic agonists, topical beta 1- blockers (reduced aqueous humour production) Miotic agents (pilocarpine) and prostaglandin analogues increase flow through the trabecular meshwork Acetazolamide (carbonic anhydrase inhibitor) also reduces aqueous humour production Primary open-angle – same drugs as for acute open-angle ▪ In those with continued optic nerve damage, can try laser trabeculoplasty Layers of the retina - review Retinal detachment Separation of the neurosensory retina from the retinal pigment epithelium Can be caused by a full-thickness retinal defect (a tear) ▪ Develop after the vitreous collapses structurally, and the posterior hyaloid (part of the vitreous) exerts traction on the retinal internal limiting membrane ▪ Liquefied vitreous humor seeps through the tear and separates the potential space between the neurosensory retina and the retinal pigment epithelium ▪ Most common type (known as a rhegmatogenous retinal detachment) ▪ Causes: Age Cataract surgery Inflammation in posterior chamber Retinal detachment Retinal detachment without retinal break (non- rhegmatogenous) ▪ May complicate retinal vascular disorders ▪ Could be caused by a problem that causes “leakage” of fluid from the choroid circulation and separates the retina from the RPE Causes - Trauma, hypertension, tumours, autoimmune disease… many causes ▪ Sometimes contractile elements develop over/around the retina and “pull” the retina off of the RPE Can accompany diabetes, retinal ischemia, and eye trauma Retinal Detachment Visualization of the different forms of retinal detachment  Retinal Detachment – Clinical features Initial symptoms commonly include the sensation of a flashing light (photopsia) related to retinal traction and often accompanied by a shower of floaters and vision loss Over time, the patient may report a shadow in the peripheral visual field ▪ May spread to involve the entire visual field in a matter of days ▪ Described as cloudy, irregular, or curtainlike This is of course urgent – needs to be seen by an ophthalmologist right away Retinal Vascular Disease - Diabetes Mellitus The effects of hyperglycemia on the lens and iris have already been mentioned ▪ Cataracts ▪ Neovascular membranes that can cause glaucoma The retinal vasculopathy of diabetes mellitus may be classified into ▪ Background (preproliferative) diabetic retinopathy ▪ Proliferative diabetic retinopathy Prognosis & Epidemiology ▪ 65,000 per year contract proliferative DR in US ▪ 8000 people in the US become blind per year from DR; leading cause of new cases of blindness Background (preproliferative) diabetic retinopathy Pathology The basement membrane of retinal blood vessels is thickened Microaneurysms are common ▪ Aneurysm = a widening of a blood vessel Macular edema Hemorrhagic exudates Pathophysiology Nonperfusion of the retina due to the microcirculatory change described above ! up-regulation of VEGF ! retinal angiogenesis Proliferative diabetic retinopathy Appearance of new vessels that sprout from existing vessels- angiogenic vessels-on the surface of either: Optic nerve head = neovascularization of the disc Surface of the retina Diabetic retinopathy – clinical features In the initial stages patients are generally asymptomatic; in the more advanced stages of the disease, however, patients may experience: ▪ Floaters, blurred vision, distortion, and progressive visual acuity loss Signs, from early to late, include: ▪ microaneurysms (quite early) ▪ A few hemorrhages (dot and flame) can occur early on ▪ General retinal edema ▪ hard exudates and cotton-wool spots (this is late) ▪ macular edema (common cause of vision impairment, late) ▪ Even retinal detachment can occur with long-standing diabetes Proliferative findings are late ▪ new vessels ▪ Many disseminated hemorrhages ▪ fibrovascular membranes (remember, can lead to retinal detachment) The cotton-wool spot Axoplasmic transport in the nerve fiber layer is interrupted at the point of axonal damage ▪ Accumulation of mitochondria at the swollen ends of damaged axons resemble cells = cytoid bodies ▪ Collections of cytoid bodies populate the nerve fiber layer infarct Seen ophthalmoscopically as cotton-wool spots Detected in a variety of retinal occlusive vasculopathies ▪ Diabetes, hypertension are the most common examples Macular Degeneration - Intro Source of central vision and allows us to see fine detail, such as recognizing a face, reading, or watching television ▪ When the macula becomes damaged, extreme and dramatic vision loss can occur The early stages of AMD typically start with the appearance of spots beneath the retina. ▪ Called drusen - small, round lesions which usually do not change vision very much. ▪ However, certain changes may occur that lead to the late stage of AMD, which is usually accompanied by vision loss. Most often, vision loss starts in one eye. Because the healthy eye compensates for the loss of vision in the damaged eye, macular degeneration may initially go unnoticed. In some cases, it will also affect vision in the other eye. ARMD - pathogenesis The etiology is unclear ▪ Associated with smoking and nutritional factors - sometimes treated with high-dose dietary antioxidants ▪ Associated with atherosclerosis and hypertension ▪ Can be familial, though difficult to identify genes – one of them might be a complement component (complement factor H) ▪ Of course more common with age However, for most cases of macular degeneration it is difficult to discern the pattern of inheritance or even the genes involved ▪ Some rare types are associated with specific genes and the inheritance pattern is better-defined ARMD – dry (atrophic, non- exudative) ARMD is either atrophic (dry) or exudative (wet) Atrophic ARMD: ▪ Diffuse or discrete deposits of inflammation-related proteins in Bruch's membrane (drusen) and geographic atrophy of the retinal pigment epithelium ▪ As the RPE atrophies, photoreceptors, and vision, are lost mostly in the area of the macula Atrophic ARMD develops slowly and insidiously ARMD - dry Clinical features: initially difficulty with night vision or changing light conditions ▪ Next difficulty reading or recognizing faces ▪ Eventually severe vision loss Most common cause of irreversible vision loss worldwide Treatments are few and not very effective ▪ Approximately 10% to 20% of patients with atrophic ARMD develop choroidal neovascular membranes = exudative (wet) ARMD ▪ Prevention is the focus – not smoking, consuming omega-3 oils and beta carotene (eat your veggies) and a carotenoid known as lutein Lutein is responsible for the yellow colour of the macula – quenches free radicals, helps filter blue light ARMD – Wet (exudative, neovascular) Exudative ARMD often progresses more quickly, and is characterized by the development of a neovascular membrane full of disordered blood vessels just below the retina ▪ This neovascular membrane may also penetrate the retinal pigment epithelium and become situated directly beneath the neurosensory retina ▪ The vessels in this membrane may leak, and the exuded blood may be organized by retinal pigment epithelial cells into macular scars This form of ARMD develops more rapidly ▪ Clinical features are similar to those of non-exudative ARMD ▪ Vision worsens more quickly, but more treatable with angiogenic antagonists and phototherapy  Drusen Not necessarily causative lesion in dry ARMD However, more drusen are correlated with worsening vision Note that you can clearly see the edges of these whitish-yellow bodies ▪ “hard” exudate ▪ “soft exudates – “fuzzier” edges