Cornea 1.pdf

Anatomy & Physiology 11.5 mm v/12 mm h (average) 540 um centrally, thicker towards periphery Avascular Nutrients/O2 - aqueous humor/tears - components Densely innervated– CN V1 sensory branches ○ Thin fiber: C-fibers ○ Pain receptors that come from th...

Anatomy & Physiology 11.5 mm v/12 mm h (average) 540 um centrally, thicker towards periphery Avascular Nutrients/O2 - aqueous humor/tears - components Densely innervated– CN V1 sensory branches ○ Thin fiber: C-fibers ○ Pain receptors that come from the cornea: ○ Trigeminal ganglion Sensory innervation Corneal layers Epithelium  ○ Epithelial stem cells: specialized cells located in the limbus Cells that play a crucial role in maintaining and regenerating the corneal epithelium Has physiological activity to heal Dysfunction may result in loss of transparency, corneal scarring, pain, and vision loss Responds to injury and can lead to scarring if injury is too high Change in structure and function because they emerge from basal cells and turnover ○ Palisade of Vogt: series of vertical, columnar cells that are arranged in a palisade-like formation Replenishment of corneal epithelial cells and for maintaining the integrity of the corneal surface Important because the junction integrity between cornea and sclera Bowman’s layer ○ Acellular superficial layer of the stroma  ○ Collagen fibers (collagen is a connective tissue) ○ Strong attachment between the basement membrane and the anterior stroma ○ Non-regenerating layer******* Stroma ○ Makes 90% corneal thickness ○ Regularly oriented collagen fibers to maintain transparency ○ Proteoglycan and modified fibroblasts (keratocytes) maintain separation of the fibers Maintain the separation of everything in the cells which gives us the transparency If there is an aberration = loss of transparency ○ Cannot be regenerated after damaged = scar Descemet’s membrane ○ Fine latticework of collagen fibers ○ Anterior/posterior banded zone ○ Has regenerative potential to a certain extent ○ When it goes all the way down to the angle, it forms the scleral spur @ that angle is the merge of both structures Endothelium ○ Monolayer of polygonal cells Maintains the balance of sodium activity ○ Sodium potassium pump ○ Adult density is ~2500-3000 cells/mm² Work w/ energy to move sodium and potassium against their concentration gradient, by doing so they maintain the cornea w/ nutrients and without getting too overhydrated (because water moves with sodium) Specular reflection  Steep angle to make specular reflection Spec meets w/ the parallelpiped and seeing the most posterior part of the parallelpiped, you will see endothelium Important specular reflection because the patient may have guttata Guttata Small, irregular excrescences or outgrowths found on the surface of the corneal endothelium Exudative material that is in the form of an outgrowth of endothelial cells or towards Descements Not a problem at first unless those endothelial cells, due to the outgrowth, cause endothelial cells to separate or expand and eventually, they drop off due to the excessive expansion ○ Once they drop off, will have less endothelial cells ○ Lose too many endothelial cells = Bullous keratopathy (constant edema, decreased vision, pain, photophobia) Fuch’s dystrophy: ***  Descemet folds Posterior edema in the cornea Normal to see after cataract sx, will go away Descemet breaks Too much water retention ^ that sometimes break May be painful and will see the lines New corneal layer Dr. Dua found a new layer located between the corneal stroma and Descemet’s membrane EM May help surgeons improve outcomes corneal grafts and transplants Also help in the pathophysiology of corneal hydrops seen in keratoconus ○ Pockets of water in the corneal stroma: hydrops and they can break and be extremely painful Superficial Epithelial Keratopathy Pinpoint epithelial disruption of the corneal epithelium ○ Can be called keratitis but it is not a true inflammation ○ Dead cells that lose their integrity ○ Should be called keratopathy rather than keratitis Not an inflammation* Many times seen without fluorescein under the slit lamp Fluorescein, Lissamine green, rose bengal Dry eye (although this is not a true inflammation, the essence of keratopathy can be due to inflammatory process which can be caused by dry eye) , infections (conjunctivitis) , medicamentosa (Drops such as Propacaine as it can cause disruption of epithelial cells) Type 1 Jrogren’s is an autoimmune disease exclusively to lacrimal and salivary glands, without any autoimmunity coming from elsewhere Type 2 Jrogren’s is associated to collagen-vascular disease (Rheumatoid Arthritis is the most common one) - RA is commonly associated to dry eye - Causes breakdown of the cells, not disruption of epithelial cells Superficial Coarse Keratitis Granular, opalescent, swollen epithelial cells sometimes presented with focal intraepithelial/subepithelial infiltrates ○ Some degree of inflammation here not only happening epithelial but also sub-epithelial ○ EKC can also cause this Can be visible w/o stain, but stain well w/ Rose Bengal & fluorescein Causes:  ○ Infections– ADV, Chlamydia, Molluscum Contagiosum (DNA-pox virus), early HSV (may lead to dendrites) and HZV ○ Medicamentosa Deep Epithelial Keratopathy Corneal sub-epithelial infiltrates (SEI) ○ Infiltration– focal or diffuse composition of inflammatory cells (WBCs) and non-inflammatory protein causing increased permeability ○ Signs Tiny epithelial foci of non-staining inflammatory opacities If it stains, it is showing epithelial dead cells sterile = epithelial breakdown is less (safe to use antibiotic and steroid) ○ Causes EKC (adenovirus serotypes 8, 19, 37) Marginal keratitis (bacterial conjunctivitis) Rosacea (meibomianitis/meibomitis) Thygeson’s Hypoxia– contact lens wear Preservatives contact lens solution ○ Treatment (these will not damage sub-epithelium) We use steroids for subepithelial infiltrates Suspensions: need to shake the bottle before use Prednisolone Acetate 1% Ophth. Susp. (PredForte) Short term, 1 drop QID Monitor IOP because long-term use increases IOP Fluorometholone 0.1% Ophth. Susp (FML) Soft steroid, long term, 1 drop QID  Does not raise IOP, even with long term use Loteprednol Etabonate 0.5%, 0.2% Ophth. Susp. (Lotemax, Alrex) Long term, monitor IOP w/ 0.5% conc. 1 drop QID Also does not raise IOP, can be used w/ artificial tears Restasis 0.5% Ophth. Emulsion (FDA approved for tx of immune-related DES) For dry eye, reduces inflammation from lacrimal gland Could be tried as off-label BID MOA: blocks calcineurin ○ Epithelial infiltrates tends to persist for a long time, especially if it was from a viral disease Have to be good at treating these as they can come back and patient complains of blurriness (can be from autoimmune response or not) ○ Recurrent corneal erosions (RCE) ○ Any damage to EBM or Bowman’s will result in weak adhesions between epithelium and anterior stroma Basal cells adhere epithelium to stroma– BM secretion Hemidesmosomes at BM attach to basal cells and to anterior stroma– also through anchoring fibrils Defective basement membrane = RCE Hemidesmosomes of the basal layer fail to adhere to the basement membrane (deficient attachment) Corneal epithelium remains loose - propensity to intracellular edema Epithelium is “oily” based, lipophilic and the stroma is hydrophilic Water does not cross the tight junctions but once there is a lesion, there is a weak barrier and the water passes from the stroma to the basal portion of the epithelium and with that, the water does not get inside the cell because they are not hydrophilic so the  water gets in between the cells and expansion between the cells in the basal portion is the epithelial erosion (edema) An abrasion is a consequence Loose epithelial layers are susceptible to separation and erosion ○ Two main causes Past injury: deep corneal (epithelial) abrasion Takes 8-12 weeks for attachments to reform if BM is destroyed When healed, it does not heal properly so now the adhesions are weak then water comes in Ask for past trauma Chronic, persistent cause as: dystrophies (Epithelial Basement Membrane Dystrophy or map-dot fingerprint dystrophy, lattice, Meesmann, Reis-Buckler, bullous (can also cause endothelium dystrophy)) Inflammation is the cause (cause weakening of the hemidesmosomes that is made up of connective tissue and collagen) and edema is the consequence There is a persistent # of leukocytes floating around, the collagenase MMP-9 enzyme is being promoted that breaks or weakens the hemidesmosomes and the water gets in between the cell = erosion ○ Symptoms Recurrent pain attacks and photophobia upon awakening or during sleep when the eyelids are rubbed or opened Friction by rubbing the lids can make it worse May have hx of trauma or family hx of corneal dystrophy, cataract surgery, refractive surgery hx, DM, rosacea Cat. Sx endothelium being affected, refractive sx., PRK Diabetes: an inflammatory disease can also promote Rosacea: a disease that is treated w/ steroids or antibiotics sometimes because it produces too much lipids; bacteria take that  and secrete a toxin that makes the skin red and then the blood vessels are inflamed and gives red color; weakens these junctions and gives us the RCE ○ Signs Positive/negative fluorescein staining Localized roughening of epithelium May present w/o signs if the pt presents at the clinic in the PM If dystrophy– bilateral map dot fingerprint patterns EBMD ○ Work-up History Recent trauma/corneal abrasion (paper cuts, fingernails) Refractive surgery Corneal transplant, cataract surgery Disease history– corneal dystrophy SLE with fluorescein ○ Treatment Acute Treat as an abrasion ○ topical antibiotic (Polytrim) and sometimes if the abrasion is big enough, use BCL but if not do not use  May use a bandage contact lens (ex: focus night and day contact lens) ○ can sleep in it but be sure to put in a new one each day Do not patch abrasions After epithelial defect is healed Artificial tears 4 to 8 day and/or hypertonic solution (5% sodium chloride solution) 4-8 times/day and ointment at hs for at least 3 mo. (Glucose 40 ointment can also be used but if not the soln.) If pt is symptomatic, edema is present in posterior epithelium and there are a lot of nerve terminals there w/ a lot of water there (edema), artificial tears are not the solution, diuretics are used to treat edema (topical in this case)—hypertonic solution such as sodium chloride more than 0.9%, 5%* draws the water and will experiencing burning sensation F/U q 3-4 weeks When corneal epithelium is loose and heaped, not healing (EMBD) Topical anesthesia Gentle debridement with moist cotton applicator, cellulose sponge, or tooth-forceps if lifted Topical NSAID ○ slows down corneal scarring but be careful w/ open flap Antibiotic ointment Bandage cl F/U daily Advise this may need to be repeated Study Study – upon injury leucocytes secrete metalloproteinases - degrade damaged BM and anchoring system In RCE there is abnormal high levels of metalloproteinases Bascom Palmer study ○ Doxycycline 50mg bid for 2 months and topical prednisolone, TID for 2-3 weeks showed no recurrence in 21.9 months ○ Conclusion - anti-inflammatory activity and metalloproteinase inhibition So recurrent/resistant cases to hypertonic tx ○ Doxycycline 50mg PO bid for 2 months ○ Lotemax QID for 1 month, then BID for 1 month ○ F/U 1month More permanent tx’s  ○ Anterior stromal puncture 25-gauge needle Multiple punctures to the anterior stroma over problem area 0.5 to 1.0 mm apart Cycloplegia, AB ointment and PP 24-48 hrs Stimulate collagen and fibronectin Leaves a subepithelial scar– only away from the visual axis ○ Stromal puncture w/ Nd-Yag laser ○ Excimer laser phototherapy keratectomy Large, shallow ablation zone Removes enough of the superficial Bowman layer to permit the formation of a new basement membrane w/ adhesion structures Corneal Neovascularization Cornea is avascular!!! Ingrowth of neo-vessels from the limbal vascular plexus into the cornea– fragile, rupture, bleed Etiology– hypoxia ○ Contact lens wear ○ Chronic inflammatory disease Trauma: mechanical/chemical Anterior segment pathology IK Mooren’s ulcer formation Terrien’s marginal degeneration  Infectious/autoimmune Graft rejection Graft vs. host disease Superficial ○ MC w/ contact lens wear ○ Limbal hyperemia and in-growth of vessels up to 4 mm into the cornea ○ Deep (PANNUS) ○ Result of a chronic inflammatory condition or anterior segment pathology ○ Leads to the development of an active inflammatory or fibrovascular >4 mm into the cornea ○ Symptoms ○ May be asymptomatic/ mild to severe decrease in vision, photophobia; contact lens intolerance Management ○ Supportive/eliminating the underlying condition ○ Topical steroid FML or Lotemax QID PredForte (can raise IOP) ○ Diathermy/laser photocoagulation ○ Limbal grafting (e.g., chemical injuries) Corneal opacities  From corneal scarring Corneal lamellae to fibrous -> scar tissue Bowman layer and below ○ Since it cannot regenerate Types ○ Nebula Mild opacification, like a fog, allows posterior details ○ Macula Denser than nebula, like a spot or stain, post details less likely seen Small central macular opacity ○ Leucoma Very dense, white totally opaque, obscuring view of iris and pupil  Leucomas ○ Adherent leucoma: when iris is adherent to leucomatous corneal opacity, following healing of perforation of corneal ulcer ○ Corneoiridic scar (flat): if iris is incarcerated in the scar tissue as a result of healing of sloughed corneal ulcer. Scar is flat. ○ Corneal Anterior staphyloma: if iris is incarcerated in the corneal tissue forming an ectatic scar ○ Peripheral Leucoma: does not interfere with visual axis, may cause some astigmatism  ○ Central: interferes w/ visual axis ○ Treatments Small corneal opacity Tattooing an options for cosmesis if it does not distort refraction of light, otherwise leave alone Large corneal opacity Anterior/ deep anterior Lamellar Keratoplasty Penetrating keratoplasty ○ Non-infectious Keratits/Keratopathy Filamentary Keratitis: from disrupted epithelial integrity  ○ Dead epithelial cells combine w/ mucin to form threads (filaments): one end is attached to a dry spot in cornea; the other end moves freely (mucousy texture) ○ Common causes KCS (keratoconjunctivitis sicca)*dry eye SLK (superior limbic keratoconjunctivitis) VXC (vernal keratoconjunctivitis) RCE (recurrent corneal erosions) EBMD (epithelial basement membrane disorder) ○ Symptoms FBS Burning Lacrimation Photophobia ○ Signs Free-floating filaments on corneal epithelium Signs of primary disease Filaments stain w/ rose Bengal/ NaFl ○ Treatment Treat underlying condition Debridement– remove the filaments w/ a jeweler’s forceps or Q-tips PF lubricants: q 2-4 hr and ung hs 5% NaCl QID and ung hs Diclofenac Sodium 0.1% (Voltaren) QID for 3-4 weeks F/U q 1-2 weeks depending on case If moderate-severe or recurrent -> 10% N-Acetylcysteine compound solution may be used QID for 3-4 weeks as it will break up the mucus If severe and not responding to tx’s above, consider bandage cl ○ Thygeson’s Keratitis ○ Bilateral, chronic, central, focal epithelial keratitis without conjunctival or stromal inflammation; “keeps no company” ○ All ages, but > in 2-3 decades; female? ○ Duration: 6 mo.-4 years Active disease last 1-2 months, then go into remission for 4-6 months and then recurs After 2-4 years, usually resolves ○ Etiology is unknown, immunological autoimmune response ○ Sub-clinical viral etiology suspected in the past has been disproven by recent episodes ○ Symptoms Photophobia FBS Lacrimation Tearing Mild decrease in vision ○ Signs Active corneal lesion– coarse, ovaloid, slightly raised, white or gray dot that stains mildly w/ NaFl; normal epithelium in b/w Inactive lesions- intraepithelial and flat, do not stain Clear eye, corneal edema A/C non-reactive ○  ○ ○ Treatment Mild Artificial tears q 1-4 hr; ung hs Moderate-severe Mild steroid such as 0.1% FML, Lotemax, Alrex: TID-QID for 1-2 weeks and taper Restasis BID (off-label) Bandage cl if no improvement or as an alternate tx during recurrence F/U weekly and then q 3-12 months Exposure keratopathy ○ Causes Bell Palsy w/ secondary lagophthalmos Nocturnal lagophthalmos or incomplete closure Behind SLE, you notice that there is a band-like SPK on the inferior cornea so ask patient to close eyes as if they are sleeping; incomplete closure so unless you have the patient on heavy lubrication and ointment QHS, patient will continue to have exposure keratopathy issues Proptosis Ectropion Trachoma can lead to ectropion Floppy eyelid ○ Symptoms FBS “Dryness” more in AM after cornea has been exposed all night ○ Signs Signs of underlying etiology SPK in interpalpebral fissure  Band shaped SPK ○ Work-up History If hx of brain trauma, order MRI Corneal sensitivity testing Exophthalmometry Evaluate Bell’s Palsy w/ or w/out Bell’s Phenomenon Up and out- Bell’s phenomenon (“better to have” because there is coverage to cornea) whereas if patient has w/o it, there is no coverage) Order orbital CT ○ Treatment Address and treat underlying cause PF lubricants q 1-4 hr; ung hs w/ lid taping F/U q 1-2 when no corneal ulcerations AB- infection or risk of infection Chronic dry eye pt w/ severe amount of SPK: do not use topical antibiotic [aminoglycosides - Gentamycin or Tobradex), can use Polytrim ** Refer for tarsorrhaphy if severe and not responding to treatment (e.g., ectropion) Neurotrophic keratopathy ○ Degenerative disease of the corneal epithelium characterized by impaired healing ○ The hallmark is decreased corneal sensitivity which leaves the cornea susceptible to injury and decreases reflex tearing ○ Epithelial breakdown can lead to ulceration, infection, melting, and perforation secondary to poor healing ○ Cause Herpes Simplex Herpes Zoster Fifth Nerve Palsy (2nd most common), others Topical anesthetics, NSAIDs do not give NSAIDs in acute bacterial conjunctivitis***** ○ Stages (The Mackie Classification for neurotrophic keratopathy) I: Rose bengal staining of palpebral conjunctiva, low TBUT, tear mucus, SPK II: Localized loss of epithelial, ovoid shape, rolled borders, stromal edema, could have cells and flare III: Stromal lysis, perforation ○ ○ ○ Management Stage I D/C topical drugs > do NOT use Acular, Voltaren, etc  Heavy lubricants PF q 1-4 hr and ung hs Stage II (we usually treat this) If large ulcer: AB ung (Tetracycline), Cycloplege w/ Homatropine and bandage cl x 24 hrs ○ Why tetracycline?? Tetracyclines are anti-inflammatory w/ collagenases that helps the healing of the cornea ○ No steroid, give homatropine that helps the symptoms that resemble slight uveitis Repeat procedure daily until healed Alternate tx for large ulcer: no BCL/patch, ab ung q 2hr, and cycloplegia w/ Homatropine BID, F/U daily ○ Do not patch and treat w/ ointment. Larger ulcers propose that they are deeper and stay away from patching. ○ Big in diameter and deeper: no bueno. Vs. big in diameter and shallow: it is ok to patch Doxycycline 100 mg PO daily has been used to promote healing Stage III Thinning and lysis of stroma: Cyanoacrylate glue w/ BCL, conjunctival flaps, amniotic membrane ○ Cyanoacrylate glue is “crazy glue”, stroma lysis that leaks septic out and can patch ○ Conjunctival flap over the lesion and keep it there; surgeons do this Larger defects may need penetrating keratoplasty