Eye Pathology P1, BMS 200, PDF

Eye Pathology P1 Conjunctival and corneal pathologies Disorders of the eye appendages BMS 200 Outcomes Describe the pathophysiological processes that underlie the main eye illnesses and relate them to their clinical features: Cataracts, keratiti...

Eye Pathology P1 Conjunctival and corneal pathologies Disorders of the eye appendages BMS 200 Outcomes Describe the pathophysiological processes that underlie the main eye illnesses and relate them to their clinical features: Cataracts, keratitis blepharitis, conjunctivitis Hypopyon, chalazion Eyelid/conjunctival anatomy and histology The eyelid, conjunctiva, and associated structures are known as the ocular adnexa (can also include lacrimal apparatus) ▪ Conjunctiva = a mucous membrane that extends over the the interior surface of the eyelids (palpebrae) and the anterior aspect of the sclera (bulbar conjunctiva) The palpebrae have a complex structure ▪ Skin on the outer surface, conjunctiva on the inner surface ▪ are supported internally by a strong, fibroelastic connective tissue known as the tarsus (or tarsal plates) ▪ Cilia on the lid margin (eyelashes) that are associated with sebaceous glands and suderiferous glands ▪ Orbicularis oculi (CN VII) and levator palpebrae muscles (SNS innervation) found beneath the skin ▪ Modified sebaceous glands in the tarsus – known as Meibomian glands – contribute to the tear film Eyelid/conjunctival anatomy and histology Glands of Zeis - small, modified sebaceous glands that open into the hair follicles at the base of the lashes Glands of Moll - modified sweat glands that open near the base of the lashes Eyelid/conjunctival anatomy and histology Left is “zoomed-out” view, right is “zoomed in” Note the complex, sebum-filled tarsal glands that empty into the duct at the edge of the eyelid Eyelid/conjunctival anatomy and histology Conjunctiva are located over the sclera - not cornea – (bulbar conjunctiva) and the inner aspect of the eyelid (palpebral conjunctiva) ▪ Stratified columnar epithelium with lots of goblet cells Secretes mucous over the surface of the eye, which contributes to the tear film ▪ Also contains accessory lacrimal glands that secretes tears ▪ Deep to the epithelial layer lymphoid follicles are found (like tiny disorganized lymph nodes) Therefore the tear film over the eye is complex: ▪ Tears secreted from lacrimal glands ▪ Lipids secreted from sebaceous-like glands – mostly associated with the eyelid ▪ Mucous from goblet cells in the conjunctiva Orbital septum – a brief word Fascial plane behind the orbicularis oculi Separates the eyelid form the orbit ▪ Important barrier to infection Infectious agents that get past the orbital septum can cause a very dangerous cellulitis known as orbital cellulitis ▪ Vision loss ▪ Intracranial infection, thrombosis of intracranial venous sinuses Life-threatening More later in Emerg Med Lacrimal glands – a brief word Innervated mostly by CN VII (great petrosal nerve, FYI) and sympathetic branches that accompany the lacrimal artery ▪ Puncta are part of the drainage routes that connect to the lacrimal sac, which in turn drains into the inferior meatus ▪ Not shown here are the accessory lacrimal glands located in the conjunctiva Conjunctivitis - overview Types: Infectious: ▪ Bacterial Staph aureus, Strep pneumoniae, H. influenzae, M. catarrhalis Chlamydial and gonococcal ▪ Viral (usually adenovirus) ▪ Parasitic, fungal 🡪 uncommon Immune-mediated ▪ Allergic, atopic, vernal ▪ Irritants (dust, smoke), toxins/chemicals  Inflammation of the conjunctiva Bacterial conjunctivitis ▪ Common infection caused by staph aureus, Strep pneumoniae, Chlamydia trachomatis, or Neisseria gonorrhea Staph aureus and Strep. pneumoniae infections are very common and are usually self-limited Chlamydial and gonorrheal infections can cause conjunctival scarring and blindness ▪ Scarring of the conjunctiva may lead to eradication of the goblet cells in the conjunctival fornix ▪ Loss of mucous production keeps tears from adhering to the cornea, leading to corneal irritation and scarring ▪ Bacterial conjunctivitis tends to have more purulent discharge and last for less time than a viral conjunctivitis Inflammation of the conjunctiva Viral conjunctivitis ▪ Extremely common Usually caused by adenovirus ▪ extremely infectious, self-limited May also be caused by herpes virus and varicella virus ▪ Antivirals for herpes and varicella conjunctivitis improve outcome Redness and swelling of the conjunctiva (hyperemia and chemosis) as well as excessive tearing (epiphora) Has a longer time course than bacterial conjunctivitis (2- 4 weeks to resolve) Clinical Features – Infectious Conjunctivitis Red eye (conjunctival injection) Eye feels itchy, sometimes like there’s a foreign body in it – rare for pain to be any more than mild Tearing, discharge, crusting of lashes in the morning (more crusting with bacterial) ▪ LN involved – pre-auricular and/or submandibular – also more likely for bacterial infection Allergic and atopic conjunctivitis will be addressed more when we talk about it in relation to rhinitis (hay fever) and asthma (BMS 250) – all are common types of Type 2 allergic inflammation ▪ To note – chemosis (swelling of the conjunctiva) is often more pronounced with these types of conjunctivitis Selected types of conjunctivitis Gonorrheal and chlamydial conjunctivitis ▪ Need to be treated urgently, since they can lead to damage to the conjunctiva (reduced ability to produce an effective tear film) and corneal damage Cornea can become ulcerated and scarred 🡪 opacity With gonorrheal infections can perforate the cornea ▪ Trachoma – typical of chlamydial conjunctival infection, leading cause of blindness in the world (not common in industrialized countries) Severe inflammation of the conjunctiva and cornea 🡪 corneal abrasion, ulceration, and scarring Large follicles can be seen (enlarged lymphatic tissue) under the superior palpebral conjunctiva (can also be seen with viral) Conjunctivitis findings The “bumpies” indicated by the arrows are follicles – seen in viral and chlamydial conjuncitivitis These “bumpies” are Trachoma (cornea is papillae – seen in allegic opaque, basically and bacterial destroyed) conjunctivitis Blepharitis Blepharitis = inflammation of the eyelids Can be multiple causes: ▪ Purulent infection of the eyelid at the margin with formation of a cyst = hordeolum (a stye) ▪ Seborrheic dermatitis (like dandruff) or rosacea can cause eyelid inflammation ▪ Allergic, drug toxicity, or autoimmune disease Sjogren syndrome = an autoimmune disorder that damages the lacrimal and salivary glands ▪ In the eye 🡪 dry eyes and minor inflammation ▪ Generalized infections – herpes or varicella (HSV-3) viruses General Clinical Features Blepharitis may cause redness of the eyes, itching and irritation of the eyelids in one or both eyes Often makes the eyes feel dry or “gritty” ▪ Often confused with conjunctivitis, more common mistake is to miss blepharitis in the elderly ▪ Eyedrops don’t tend to help much Untreated blepharitis, in particular due to rosacea, can lead to conjunctivitis ▪ Severe cases 🡪 corneal inflammation and scarring (keratitis) and Infections of the eyelid Hordeolum (stye) ▪ Purulent bacterial infection of a sebaceous or suderiferous gland (either accessory sebaceous glands or Meibomian glands) Tends to be caused by Staph aureus ▪ Small, inflamed, very tender bump appears on the margin of the eye (smaller, more tender than a chalazion) Often resolve without treatment, though warm compresses and good hygeine aid resolution and prevent future recurrences Infections of the eyelid Chalazion – not that “infectious”, more of a granulomatous inflammation: ▪ Lipid products (from breakdown of bacteria or blocked sebaceous secretions) penetrate into the tarsal tissue Elicits a granulomatous inflammation ▪ An inflamed, mildly tender “bump” appears on the eyelid (usually upper eyelid since the glands are longer) ▪ Very common and generally benign, usually treated with heat and massage (though sometimes antibiotics are necessary) They do tend to need treatment to resolve, though Keratitis Usually caused by HSV-1 (usual cause of cold sores) but can be caused by HSV-2 (genital herpes) ▪ Does not tend to cause severe damage on initial infection ▪ After “resolution” of an HSV infection, it lives latent in the trigeminal ganglion and can periodically migrate down the nerve and cause reactivation of symptoms ▪ Reactivation more typically causes a more severe inflammatory reaction in the cornea 🡪 ulceration Reactivation of HSV causing keratitis is often associated with: ▪ Stress, excess exposure to sunlight ▪ Fluctuations in reproductive hormones throughout the menstrual cycle  HSV Keratitis Pathogenesis: ▪ Typically causes many small intraepithelial ulcerations with opacities that occur due to edema just below the epithelium ▪ If chronic (see below) then the stroma is thinned and scarred, edema in the stroma, and abnormalities in the corneal endothelium (see arrows) Clinical Features: ▪ Pain, tearing, foreign-body sensation ▪ Red eye ▪ Can have modestly decreased vision unless damage is severe (scarring)  HSV Keratitis Herpes zoster ophthalmicus – Herpes zoster (HSV- 3) ▪ Dermatitis in the dermatomal distribution of CN V1 that is typically unilateral Hutchinson’s sign: if tip of nose is involved (nasociliary branch of V1) then globe will be involved in ~75% of cases If no nasal involvement, eye is involved in 1/3 of patients ▪ Clinical Features Pain, tearing, photophobia, red eye, corneal edema Corneal hypoesthesia ▪ Complications Keratitis, ulceration, perforation and scarring Secondary iritis, secondary glaucoma, cataract Occasionally severe post-herpetic neuralgia The Eye – Part 1b Physiology and Neurophysiology BMS200 Outline - Physiology Continued: Retina Overall structure and function (last day) Retinal Cells: Rods and Cones Structure and function continued (started last day) Signal transduction Adaptation Visual Processing Retina - Bipolar Cells What is their role in processing visual information through receptive field organization. The mechanism on the next slide contributes to something called, lateral inhibition a critical process in visual perception. It ensures that the brain receives sharpened signals about contrasts in light and dark areas, enabling fine discrimination of edges and patterns in the visual field. Let’s discuss the mechanism……. Rod and Cone Bipolar Cells: Rod Bipolar Cells: These are associated with scotopic vision (low light) and are "on-center" cells, meaning they are activated when light falls on the center of their receptive field and the center is brighter than the surround. Cone Bipolar Cells: These are associated with photopic vision (bright light) and come in two types: On-center: Similar to rod bipolar cells, activated when light hits the center of their receptive field, and the center is brighter than the surround. Off-center: Activated when light falls on the surround of their receptive field, and the surround is brighter than the center Receptive Field Organization: The receptive field of bipolar cells has a center-surround organization: On-center receptive fields are stimulated when the center is brighter than the surround. Off-center receptive fields are stimulated when the surround is brighter than the center. Oppositional Regulation: "On-center" and "off-center" cells have opposite responses to the same stimulus. This antagonistic relationship enhances contrast and edge detection, improving visual acuity and allowing the brain to better discern shapes and details. When on-center are stimulated then off-center are inhibited, and vica versa FYI ONLY Surroun Center Surroun Surroun Center Surroun d d d d Cone s Hyper- Depol. pol. Decrease Increase d Glu d Glu Off- On- Bipola Off- On- center center center center r Decrease Decrease d Glu Increased d Glu Glu Outline - Physiology Continued: Retina Overall structure and function Retinal Cells: Rods and Cones Structure and function Signal transduction Adaptation Visual Processing Adaptation After activation, In the dark, rhodopsin needs to be regenerated before cells can respond again Trans retinal separates from the opsin (G-protein coupled R) Opsin = “bleached” and no longer active Trans-retinal travels to pigment layer, converts back to cis retinal Cis retinal travels back to rods recombines with the opsin, ready to respond to light again Slow process; similar but faster for cones which is why rods are not effective at adapting to rapid changes in light conditions. This slow regeneration limits rods' ability to function well in bright light after exposure to darkness (e.g., adjusting to bright light from a dark room).  Light G-protein signaling Meta- Rhodopsin cascade Fast rhodopsi Opsin (G- Opsin + n protein Trans- coupled R) + retinal Opsin Trans (“bleached” retinal Cis-retinal Dark To pigment Slow ) layer Back to Cis rods retinal Why can’t you see right away when you move from sunlight into a dark room? Why are you temporarily “blinded“ when you move Moving into a dark room When moving into a dark room, the pupil immediately dilates to let in as much light as possible Why does it still take time for you to be able to see? Photopigments that were bleached in the light need time to regenerate in the dark Even once photopigments are regenerated, you can only see in grey-tone – why? Moving into sunlight When moving into sudden, intense sunlight, many photoreceptors activate all at once You can be temporarily “blinded” by the overstimulation Your pupil immediately constricts and you squint to reduce the amount of light entering the eye As you adapt to the bright light: Rods don’t regenerate fast enough, so become saturated Stop responding They become saturated (fully bleached) and thus cannot respond to additional light stimuli. Cones regenerate faster than rods, so don’t saturate Continue to respond Vision becomes mediated by cones Outline - Physiology Continued: Retina Overall structure and function Retinal Cells: Rods and Cones Structure and function Signal transduction Adaptation Visual Processing Visual Processing Bipolar cells already start to process visual signals at the level of the retina Review: Respond differently to different patterns of light Ex: on-center vs off-center illumination Other retinal cells involved in visual processing: Horizontal cells Ex: Help sharpen contrasts FYI: Modify signals at level of photoreceptors/bipolar cells Amacrine cells Ex: Help detect changes in vision, such as movement, lights going on/off FYI: Modify signals at level of bipolar/ganglion cells  Visual Processing Ultimately, visual signals from rods and cones are transmitted by ganglion cell axons to the brain Form the optic nerve Photoreceptors 🡪 Bipolar cells 🡪 Ganglion cells Graded 🡪 Brain All-or-none receptor action potential potential How would increasing light intensity affect the receptor potential? ▪ What about the action potential? Therefore, how does the brain register increased light intensity? Outline - Neurophysiology Optic Nerve Brain: Visual Processing Cranial Nerves – General Review Oculomotor Nerve Trochlear Nerve Abducens Nerve Objectives Describe the structure, pathways, and connections between the optic nerve and the brain, including the visual pathway from the retina to the primary visual cortex and as well as role in accommodation and pupillary reflexes. Given the basic pathophysiology of glaucoma and macular degeneration, predict the resulting visual field defect Predict the anatomical region affected by a given a visual field defect Describe the fundamental concept of visual perception and the process by which the brain converts visual data into a coherent visual perception.. Objectives. Describe how damage to the somatic motor component of the oculomotor nerve would contribute to strabismus and decreased depth perception, diplopia, ptosis, downward and abducted eye Describe the role of the oculomotor and trochlear nerves with respect to intorsion and extorsion of the eye, and how damage to the trochlear nerve would manifest. Describe how the abducens, trochlear and oculomotor nerves, as well as the medial long fasciculus, interact to mediate the vestibulo-ocular reflex. Describe how damage to the abducens nerve would contribute to strabismus and decreased depth perception, diplopia. Optic Nerve Optic nerve: formed by axons of ? Exit from back of eyeball creates the ? 50% of fibers cross at the optic chiasm (where is this located, anatomically?) and join contralateral fibers After the chiasm, optic nerve fibers form the optic tract Optic tract synapses in thalamus (FYI: lateral geniculate body) Leaves thalamus as optic radiations Optic radiations synapse in visual cortex (occipital lobe) A = optic nerve B = optic chiasm C = optic tract D = optic radiations Predicting visual defects Use the diagram on the next slide to trace the nerve fibers from the site of the lesion 🡪 retina 🡪 out to visual field Those are the areas of the visual field that the eye cannot see, they are coloured black in a visual field diagram  Left Right eye eye Name of visual visual Defect A field field Bitemporal B hemianopia Right A C homonymou C s D B D hemianopia Radiations: Upper E E fibers from both eyes F travel more F laterally, lower fibers more medially Visual Field Diagrams Fibers from what part of the eye do you think are spared in this form of hemianopsia? Name the condition Draw the visual field diagram of a central scotoma resulting from macular degeneration Scotoma = an area with vision loss in an otherwise normal visual field What does this visual field diagram of end-stage glaucoma tell you about how the disease progresses? Outline - Neurophysiology Optic Nerve Brain: Visual Processing Cranial Nerves – General Review Oculomotor Nerve Trochlear Nerve Abducens Nerve Role of the brain in vision Scenario: Burning your finger on a hot stove (ouch!) Primary visual Primary I see some cortex My finger somatosen shape that is feels - Registers sory cortex some sort of heat… colour… shape & colour of stove (would - Registers also register finger is hot My finger is I see a blue Secondary movement) Secondary burning stove (funky)! visual cortex somatosensory hot…help!! - Recognition of cortex colour & shape - Recognition of OOPS!! “how hot” Parieto-occipito-temporal association cortex Combines visual and tactile info to Primary Secondary somatosensory somatosensory Seconda ry visual Primar y visual Parieto-occipito- temporal https://commons.wikimedia.org/wiki/ Pathologies of vision: brain Visual cortex can begin to “ignore” images from an eye that has a visual defect Ex: Eye wanders, is myopic (uncorrected), etc Vision associated with the affected eye is worse than would be explained by the visual defect alone Known as amblyopia How could you treat this? Lesions in the primary visual cortex result in cortical blindness Review at home using next slide: What would the visual field look like in someone with a right primary cortex lesion? A = optic nerve B = optic chiasm C = optic tract D = optic radiations Lesion in right primary cortex would result in what visual field defect? Pathologies of vision: brain Lesions in the secondary visual cortex can result in: Movement agnosia An object appears in another location, movement not noted Visual agnosia Inability to Inability to identify common objects view object Inability to copy drawings as a “whole” Colour agnosia Cerebral achromatopsia: cannot recognize colours even though cones are fine See in grey-scale Outline - Neurophysiology Optic Nerve Brain: Visual Processing Cranial Nerves – General Review Oculomotor Nerve Trochlear Nerve Abducens Nerve Review Table Muscle Nerve Action Medial rectus CN III (somatic) - Oculomotor Adduction of eye (look to nose) Lateral rectus CN VI - Abducens Abduction eye (look to ears) Inferior rectus CN III (somatic) Downward eye, extorsion Superior rectus CN III (somatic) Upward eye, intorsion Inferior oblique CN III (somatic) Elevated and abducted eye Superior oblique CN IV - Trochlear Downward and abducted eye Levator palpebrae CN III (somatic) Elevated upper eyelid superioris Ciliary muscle CN III (visceral: parasymp) Contraction leading to increased convexity of lens Pupillary sphincter CN III (visceral: parasymp) Miosis (pupillary construction) Memory help: Review at home To remember where the cranial nerve nuclei are located: Divide into 3 equal groups based on number Label from midbrain to medulla Add in exceptions (I, II), III, IV: Midbrain Exceptions: I and II. Rather than midbrain, I (optic) is retina and II (olfactory) is olfactory bulb V, VI, VII, VIII: Pons Exceptions: V is trigeminal, so stretches through all 3 parts of brainstem (pons, medulla and midbrain) VII and VIII are near the border and also stretch into medulla IX, X, XI, XII: Medulla  Nose (olfactory epitheliumEye ) (retina) I and II (olfactory & optic) are not found in I II III IV Midbrai brainstem 1 n V= Trigeminal 2 V VI VII Pons VIII = found in all 3 3 VII, VIII = on border of pons/ locations medulla, also spill into medulla IX X XI XII Medulla Outline - Neurophysiology Optic Nerve Brain: Visual Processing Cranial Nerves (extraocular muscles) – General Review Oculomotor Nerve Trochlear Nerve Abducens Nerve Oculomotor (III) Nuclei are found in: ? Oculomotor motor nucleus (somatic motor) Motor innervation to all muscles that move the eyeball except: 1) ? Action: Down and abduct 2) ? Action: adbuct Also motor innervation to levator palpebrae superioris Action: Edinger-Westphal nucleus (EDW) (visceral motor) Parasympathetic innervation to Pupillary sphincter Action: miosis (?) Ciliary muscle Action: ? Oculomotor (III): Somatic Given that external opthalmoplegia is a weakness in one or more eye muscles: What symptoms of external opthalmoplegia could result from damage to the somatic portion of CN III? Provide a rationale One symptom: which way would the eye point? A: Down and abducted B: Down and adducted https://commons.wikimedia.org/wiki/ File:Oculomotor_nerve_palsy.png C: Up and abducted D: Up and adducted Oculomotor (III): Visceral If the visceral component of CN III was also damaged (FYI “internal opthalmoglegia”), what additional signs or symptoms would you expect? Provide a rationale Hint: Think “accommodation ”… Oculomotor (III) - Reflexes Accommodation reflex (CN II and III) ▪ As an object moves closer, its retinal image becomes out of focus Activation of the accommodation reflex focuses the image by: ▪ Convergence of eyes Muscle engaged? Involves activation of which CN III nucleus: motor or EDW? ▪ Increased convexity of the lens Muscle engaged? Involves activation of which CN III nucleus: motor or EDW? ▪ Constriction of pupil Muscle engaged? Involves activation of which CN III nucleus: motor or EDW?  Visual Cortex Optic ? EDW Motor nucleus nucleus CN III Thalamus CN Optic III Ciliary CNI nerve ganglion and ? Short ciliary nerves Ciliary muscle Medial Medial Ciliary muscle (lens) Pupillary Rectus Rectus (lens) Pupillary sphincter sphincter Cute pig approaching! Eyes  Oculomotor (III) - Reflexes Pupillary reflex (CN I and CN III) Light in one eye causes constriction of both pupils Which CN III nucleus is involved: motor or EDW? Lippincott Illustrated Reviews: Neuroscience, 2e Claudia Krebs, Joanne Weinberg, Elizabeth Akesson, Esma Dilli Oculomotor (III) - Reflexes Both accommodation and pupillary reflexes use the EDW nucleus Pupillary reflex involves the pretectal area of midbrain, accommodation reflex does not How does damage to the pretectal area affect the ability of the pupil to constrict: Can it constrict in response to bright light? Can it constrict to accommodate? FYI: This is known as Argyll-Robertson pupil and results from neurosyphillis Outline - Neurophysiology Optic Nerve Brain: Visual Processing Cranial Nerves (extraocular muscles) – General Review Oculomotor Nerve Trochlear Nerve Abducens Nerve  Trochlear (IV) Nucleus found in: ? ▪ Muscle innervated is contralateral superior oblique Action: eye down and abducted Additional action: Intorsion ▪ Rotation of eye towards the nose It’s a SIN you Note: Inferior have to remember oblique (oculomotor nerve) does extorsion: rotation towards ear this, but… Why do we care about intorsion/extorsion? Superior oblique = Intorsion =  Trochlear (IV) Red arrows = rotation of eye needed to keep image upright What What nerve/muscle in nerve/muscle in right eye is left eye is engaged? engaged? https:// not commons.wikimedia. org/wiki/ File:Vestibulo-  Trochlear (IV) If the trochlear nucleus on the right side is damaged and the patient looks straight ahead: ▪ The affected eye is the _(R/L?)_ eye In this eye the ____ muscle will be compromised, allowing its “partner muscle”, the _____ , to dominate ▪ This will cause the affected eye to rotate towards the ___(ear/nose?)__ (“___-torsion”) All of this will create double-vision (diplopia) Which way might a patient try to tilt their head to put the affected eye in the correct position to resolve the diplopia? - This compensation means a patient may come in complaining of neck pain rather than blurry vision! Outline - Neurophysiology Optic Nerve Brain: Visual Processing Cranial Nerves (extraocular muscles) – General Review Oculomotor Nerve Trochlear Nerve Abducens Nerve Abducens (VI) Nucleus found in: Pons ▪ Muscle: lateral rectus Lateral Medial Action: Abduction rectus, CN rectus, CN Helps mediate lateral gaze VI III ▪ Coordinated by the reticular formation in the pons (PPRF) FYI: Paramedian pontine reticular formation ▪ Involves what two muscles/nerves? All 3 extra-ocular nuclei (CNIII, IV, VI) are connected by a tract ▪= Medial Longitudinal Fasciculus (MLF)  MLF MLF III III IV IV Midbrain Pons VI VI PPRF Lateral Medial rectus rectus Abducens (VI) Along with CN III and IV, CN VI plays a role in the vestibulo-ocular reflex Allows eyes to remain fixed on an object even when the head moves Movement is picked up by the vestibular apparatus Signals are sent to the PPRF (reticular formation in pons) Nerves to the appropriate extra-ocular muscles are engaged by fibers running through the ?  X X Moveme Moveme nt of nt of head eyes MLF MLF In this scenario, which muscles III III are engaged to counter-act the IV IV movement of the head? VI VI PPRF Abducens (VI) Consider the position of a patient’s eyes if they have damage to the left abducens nucleus and are asked to look to the left without moving their head ▪ R eye will look to the left (ie towards nose) R eye is fine: CN III innervates medial rectus & adducts eye ▪ L eye will still look straight ahead or deviate slightly medially Lateral rectus is compromised, not strong enough to abduct eye Clinical considerations include: R L ▪ Decreased depth perception ▪ Diplopia Medial Lateral rectus rectus works compromis 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 Type Primary Site of Includes Inflammation Anterior uveitis (90%) Anterior chamber Iritis/iridocyclitis/anterior cyclitis Pars planitis/posterior Intermediate uveitis Vitreous cyclitis/hyalitis Focal, multifocal, or diffuse Posterior uveitis Choroid choroiditis/chorioretinitis/retinoc horoiditis/retinitis/Neuroretinitis Anterior chamber, vitreous, Panuveitis 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 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 = neovascularizat 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