Cornea and Conj - Ant Seg Disease PDF

Allergic Eye Disease Condition Definition/ Characteristics/Eitiology Signs/Symptoms/ Manifestations Treatment Conjunctival inject...

Allergic Eye Disease Condition Definition/ Characteristics/Eitiology Signs/Symptoms/ Manifestations Treatment Conjunctival injection and chemosis, tearing, pruritis, eyelid Affects up to 30% of the population swelling Seasonal & perennial Allergic Conjunctivitis Papillary reaction Bilateral Many patients self-medicate Itching, photophobia, blurred vision, copious mucoid Atopy discharge, ptosis, shield ulcer eczema, hayfever and asthma starting early in life 2 main disease subtypes: Bilateral Vernal keratoconjunctivitis (VKC) Palpebral Chronic with seasonal exacerbations and remissions Limbal Improving around puberty Mixed also possible Follicles (or papillae?) VKC - Limbal Gelatinous appearance Can be confluent Occur more often in black pts Can be associated w/ Horner Trantas Dots Small white elevated epithelial lesions Limbal form of the disease Found at any meridian along limbus Limbal follicles (or papillae?) Contain eosinophils & epithelial cells occurring in absence of marked tarsal papillae Promote KNV Black & Asian patients Heavy infiltration of inflammatory cells Greyish, gelatinous swellings Superior limbus Pseudogerontoxon Can develop in recurrent limbal VKC Paralimbal band of superficial scarring  Chronic periocular atopic dermatitis Atopic Keratoconjunctivitis (AKC) Dennie-Morgan Lines eyelid hyperpigmentation (orbital darkening) Itching= major symptom Watering, blur, pain Work with allergist/PCP Worse in presence of fur-bearing animals Allergy Testing to better define nature of irritants Redness, scaling, dryness of external lid & margin Systemic medication: subcutaneous omalizumab injection (binds to free IgE); montelukast p.o. (leukotriene receptor antagonist) Papillary rxn Allergen desensitization Associated with atopic dermatitis Conjunctival hyperemia Remove allergens Environmental airborne allergen sensitivity Madarosis Topical antihistamine-mast cell stabilizer Onsets 2nd-5th decade Lagophthalmos Topical mast cell stabilizer year round ~ 2:1 male: female ratio Cicatricial ectropion Blepharitis Tx Perennial Shield Ulcer Topical steroids Worse in winter Keratoconus Topical steroid sparing options Low expectation of resolution PED Tacrolimus – *ophthalmic ung or gtts must be compounded* IgE & lymphocyte mediated Presenile cataracts Cyclosporine Anterior subcapsular shield like or stellate As needed: Posterior subcapsular Cataract Surgery (CE/IOL) Allogenic Limbal Stem Cell transplantation Atopic pt’s ↓’d systemic cell-mediated immunity ↑’d susceptibility to herpes simplex keratitis & lid colonization with staph a. Giant papillary conjunctivitis (GPC) Localized giant papillary conjunctivitis Aka Contact Lens Papillary Conjunctivitis (CLPC) Traditionally viewed as non-immunogenic response Usually occurs in zones 2 and 3 2/2 repetitive microtrauma, usually CL’s (penetrating Moderate CL associated GPC keratoplasty & sutures) Papules between 0.5 and 1 mm in size However, Type 1 & 4 HS rxns also implicated Healthy, non CL wearing pt’s + conj hyperemia, mucus strands often have papillae Symptoms often precede signs Ex. 0.3 mm in size Presence of mucus in am Not larger than 1 mm D/c CL wear (holiday) Itching post lens removal Papillary rxn > 0.3 mm= abnormal (GPC) Start anti-histamine/mast cell stabilizer combo Can progress to CL intolerance Junctional zones often feature a papillary rxn → Not E.g. Pataday (olopatadine 0.2%) QAM pathologic If $ is an issue: cromolyn sodium 4% TID-QID Proposed pathophysiology of CL-GPC If $ is no issue: bepotastine besilate 1.5% BID CL coated with deposits= antigen stimulus If severe, start soft steroid QID x 6 weeks (check IOP; consider taper) Production of antibodies E.g. Loteprednol 0.5% or fluoromethalone (FML) 0.1% Complement system activation Switch to daily CL wear (if in softs) Mast cells and basophils release histamine If in RGP, ↑ freq of enzymatic/alcohol based cleaning & switch to hydrogen peroxide disinfection CL becomes more coated More lid related microtrauma and production of cytokines Attraction of eosinophils, mast cells, basophils, lymphocytes and plasma cells to conjunctiva Vicious cycle continues/worsens  Viral & Bacterial Conjunctivitis Condition Definition/ Characteristics/Eitiology Signs/Symptoms/ Manifestations Treatment Vitamin A deficiency Partial night blindness: 1st symptom 200,000 IU Vitamin A now, tmrw, 2-4 weeks (recommended daily dose of vitamin A= 1,000 IU) Xeropthalmia: corneal & conjunctival dryness 100,000 IU for child < 1 yr Causes: Can progress to: Malnutrition in developing countries K ulceration→ perforation Developed countries Keratomalacia (severe wrinkling/opacification esp in kids) GI Malabsorption Goblet cell development requires Vitamin A Alcoholism deficiency= ↓mucin layer = keratin build-up on conj (Bitot’s spots) most commonly temporal Discharge subtypes: Etiology: Watery Bacterial, viral, allergic, cicatricizing Acute Allergic, Viral Duration: Mucoid Acute Chronic Allergic, dry eye mostly infectious causes Purulent/mucopurulent Conjunctivitis duration of 2 weeks ± blood in cough ± voice hoarseness Phlyctenulosis: Possible TB association TB infection = newer term for latent TB Weight loss; Fever; Night sweats Phlyctenule?... When to consider testing for TB Positive screening test result, (-) chest X ray Individuals with increased risk of new TB infection Tuberculosis disease= newer term for active TB Contact(s) of pt(s) with untreated resp. TB disease Positive screening test result, (+) chest X ray Illicit drug use Residents or employees of a homeless shelter or correctional facility Healthcare workers History of travel to TB endemic region(s) Individuals with increased risk of TB re-activation (from TB disease) HIV Transplant, chemotherapy, or other immune compromising cond. TB Testing: no test to definitively establish Dx of TB infection 2 screening tests: 1 Purified Protein Derivative (PPD) aka tuberculin skin test OR Mantoux test 2 QuantiFERON TB Gold Plus (QFT-Plus)= blood test no clear advantage of QFT-Plus VS PPD to predict future risk decision should be based on the setting, cost and availability  Treatment Pediatric Blepharokeratoconjunctivitis (BKC) Topicals: Short term topical steroids Cyclosporine 0.05% B.I.D. Tacrolimus 0.03% ung B.I.D. Topical azithromycin Aka blepharoconjunctivitis Erythromycin ung Q.H.S Avg onset age= ~ 6 yrs old Conjunctival changes= phlyctens, follicular or papillary More severe→ Asian & Middle Eastern hyperplasia Orals: Recurrent episodes of blepharitis Corneal manifestations: phlyctenules, PEE/SPK, Pannus Erythromycin 40 mg/kg/d p.o. ± recurrent hordeolums and/or chalazia Reduce as low as 125 mg p.o. q.o.d. x 6-8 m + eye rubbing, photophobia Azithromycin 10 mg/kg/d for 3 days Repeat regimen for 3 weeks Lid hygeine/maintenance: Warm compress PF AT’s MG expression Lid scrub or spray with antimicrobial activity E.g. Ocusoft Plus /Hypochlorous Acid Responds well to Ab-steroid combo gtts Inflammatory rxn to staph antigen Marginal Keratitis Cases of mild bleph? Steroid Q.I.D. + Antibiotic Q.I.D. Common in rosacea (MGD) If no epi defect (ED) Unilateral or bilateral Infiltrates less than 1.5 mm w/ intact epi don’t require cultures Creamy, white elliptical infiltrates Can use combo gtts Begins with 1 or more localized peripheral stroma Occurs near point of intersection of (+) ED & unsure sterile or infectious etiology? infiltrates eyelid margin and limbus antibiotic (PF Moxi preferred) q1-2h, see pt back in 1-2 days Separated by from limbus by 1-2 mm When could you then add steroid? When ED is recovered Multiple infiltrates can coalesce circumferentially ED is typically smaller than the infiltrate size in marginal Typically begins with an intact K epithelium keratitis *do not forget eyelid hygiene* Overlying Epithelium can break down (ulcerate) Blood vessels (pannus) from limbus Ddx= microbial keratitis or early peripheral ulcerative may form once necrosis occurs keratitis (PUK) Recurrences are common Untreated ant blepharitis Significant MGD PEE Marginal Keratitis Rosacea Corneal Manifestations Stromal Keratitis Corneal scarring & KNV = Pannus  Pt’s with + cultures typically have infiltrates associated w/: Pain AC rxn Mucopurulent discharge Culture (+) ED overlying infiltrate K infiltrate that is large, central > 2 mm AND/OR Even in absence of ED, K edema surrounding infiltrate or associated with stromal involvement/melting= likely presence of an AC rxn suggests infection infectious Infectious Hypopyon Risk factors for infectious infiltrates: Whitish-yellowish layer of WBC Overnight CL wear, poor CL hygiene Corneal ulcer → iritis Smoking (via diffusion of bacterial toxins) Recent K compromise Document (+) or (-) hypopyon w/ any K ulcer Won’t necessarily aid in specific etiology Height of hypopyon can help monitor tx efficacy Is a hypopyon typically sterile? Yes When not? endophthalmitis Infiltrates Sterile immune hypersensitivity rxn Rxn to staph antigen from lid margin (marginal keratitis) Acute & Chronic Hypoxia (CL wear esp EW) Contact lens peripheral ulcer (CLPU) Auto-immune disease (e.g. RA, Crohn’s) *A large # of pts with “sterile” ulcers are actually culture + and Post corneal cross-linking for KCN should be treated with antibiotics No epi defect CL wear→ K hypoxia Blepharitis Can be severe/diffuse (provided no overlying ED) Contact lens peripheral corneal ulcer (CLPU) Treat as infectious given significant noticeable ED 4th gen FQ Q1H then taper pending response Typically= single small infiltrate Minimal or no overlying ED Sterile infiltrate? Mild discomfort without frank pain (-) AC rxn Patching Risk: Bacterial Keratitis Cooler climates: Abrasions should never be patched (esp in a CL wearer!!) Gram + predominate ~70 % Can become a serious infection (e.g. Pseudomonas) overnight Tropical climates: Patching prevents topical antibiotic use Gram (-) bacteria more frequently cultured Symptoms/signs: May ↑ surface temp Conj injection & chemosis Allows bacterial growth Contact lens related infections Decreased vision, pain Relatively static post-CL tear environment Photophobia, tearing Most common risk factor for bacterial keratitis in Purulent discharge urbanized pop. No consensus of characteristics that identify infectious keratitis Mini-abrasions, hypoxia, changes to ocular surface as bacterial in origin microbiota 40% of culture proven cases associated with sleeping or swimming in CL’s  Case Hx General: Blurred vision? Pain? Discharge? Light sensitivity? Pace of disease evolution Acanthamoeba and Fungal = slowly Nocardia , Moraxella , Haemophilus , and Mycobacterium = slowly Corneal Ulcer documentation Pseudomonas, staph and strep = quickly Ulcer severity described in terms of dimensions of the lesion Drops: Antibiotics, Steroids or other started? Express degree of K thinning Homeopathic remedies? Abuse of topical eye gtts? Topical anesthetics? Indicate location of maximum thinning Corneal Ulcer Topical steroid use? = fungal risk Hypopyon expressed as maximum vertical height Contact lens wear? EW? Extent of K edema Acanthamoeba RF: Tap water? Swimming in fresh water? Trauma? Photograph if possible; if not sketch diagrammatic representation Vegetative matter (e.g. branch) = fungal Recent eye Surgery? Sutures? Medical history: Perioral cold sores? H/o facial shingles? Prior Dx herpes simplex or zoster? RA? SLE? Granulomatosis with polyangiitis? Corneal Culturing for Bacterial Keratitis When in doubt, culture (or refer for culture) Culturing with scrape Viable bacteria found at peripheral edge of the Apply proparacaine 0.5% gtt infiltrate or deep within the ulcer Do not collect only purulent material Perform separate corneal scrape for each plate Potential K culturing tools: *sterilized instrument each time B= Kimura spatula Apply enough pressure to indent cornea slightly C= blade Suspect fungal? D= culturette swab Scrape needs to be deep E= calcium alginate swab Significant K thinning? *can sterilize spatula over flame of alcohol lamp bt/w Avoid point of thinning each separate culture or slide; ensure tip temp has Apply less pressure to avoid perf returned to normal before touching K Refer Antibiotic Susceptibility Testing (in vitro) Culture Bacterial K isolates should be tested for susceptibility Use C streak pattern to Ciprofloxacin, ofloxacin, moxifloxacin, cefazolin, Why? Non-diminishing culture returns = likely contamination vancomycin, gentamicin, tobramycin, sulfacetamide, polymyxin B, bacitracin Sterile cotton tipped applicator Minimum Inhibitory Concentration (MIC): Thioglycolate broth Lowest concentration of a drug that prevents the Quick culture visible growth of bacteria (or fungi) Place directly into vial/broth Broth or agar dilution Do not touch eyelids Disc Diffusion: Only handle portion not going into vial Paper discs impregnated with set amount of antibiotics on lawn of bacteria 24 hrs of incubation, zones of inhibition are measured and compared to standards Susceptibility, intermediate susceptibility, resistance **Corresponds to serum/blood levels instead of ocular levels** Culturing Result: medication susceptibility E-swab Susceptible Flocked swab Intermediate Short Nylon fibers with brush like texture to dislodge & collect cells Only susceptible at high doses Capillary action facilitates strong hydraulic uptake of liquid samples Resistant Sample stays close to surface Organism not susceptible Allows for fast and complete elution **Culturing may yield a + Only in ~50% of cases Even worse chance if pt already on an antibiotic. May After culturing... need 24 hr med washout. Swab placed in 1 mL of modified Amies medium Maintains bacterial sample viability for 48 hrs (24 hrs for Neisseria) Inoculated Amies medium aliquoted in lab into ten 100uL samples  Bacterial Keratitis Stages Bacterial Adherence Pili or fimbriae Damaged K epithelium ↑↑↑ adherence of pseudomonas, S. pneumonia & S. aureus A. Progressive Infiltration i. Adherence & Entry of organism → neutrophils arrive Bacterial Invasion into Stroma & Cytotoxic effects shortly after Proteases, exotoxins degrade epi extracellular matrix and BM ii. Diffusion of toxins & enzymes Causes cells to lyse iii. Resultant tissue destruction Stimulation of immune response results in further damage B. Active Ulceration Release of ROS intermediates & host proteases, which further i. Tissue necrosis→ ulceration (epithelium degrade extracellular matrix and BM desquamation) ii. Phagocytosis of organisms and cellular debris Stromal Necrosis iii. Vascularization can occur if ulceration is of long Bacterial exotoxins and proteases continually released duration Persist in K for a prolonged time→ Continued stromal C. Regression destruction i. Improvement in signs and symptoms Can attract PMN leukocytes via complement pathway ii. Relatively smooth and transparent ulcer area D. Cicatricization Stromal Ring Ulcer/Infiltrate i. Replacement with fibrotic/scarred tissue Can occur with ii. Re-epitheliziation Pseudomonas Bacillus Cereous Post trauma or wound contamination Acanthamoeba Nocardia Fungus Bacterial Keratitis Subtypes  Culture of Staph Aureus Staph aureus K ulcers: Pearly white growth on blood agar Gram (+) Bacterial Keratitis Round, well circumscribed infiltrates What do ↓ing #s of colonies on consecutive C streaks tell us? No contamination of the plate (+) suppuration Deep stromal abscess possible Type of hemolytic rxn on blood agar→ used to classify streptococci Hemolysis= breakdown of RBC Strep. pneumoniae: β-Hemolysis= is associated with complete lysis of RBC surrounding the colony, whereas Associations: α-hemolysis=partial or “greening” hemolysis (reduction of RBC hemoglobin) Post trauma Dacryocystitis Staph , Strep, Corny constitute > 70% of reported Filtering bleb infection ulcers worldwide Ulcer appearance: Coagulase (-) Staph (e.g. epidermidis) Deep stromal abscess Currently more than 30 species Marked AC rxn major nosocomial pathogen + hypopyon Older pt’s, BCL wearers, pts with Acute Course: compromised oc. surface Rapid progression Staph aureus Perforation= common Coagulase + Methicillin sensitive (MSSA) & Methicillin Ulcus Serpens Resistant (MRSA) Hypopyon + corneal ulcer caused by s. pneumococci both frequently recovered from tendency to creep over K healthcare exposure (K transpl, CL wear, CE/IOL) Strep pneumoniae (less common) Infective Crystalline Keratopathy→ Strep viridians Strep viridians (less common) inflammatory response = minimal encased in biofilm Risk Factors: Corticosteroid use CL wear (e.g. extended wear) Previous K surgery Topical anesthetic abuse Chemical burns Do these have a suppurative infiltrate? No. Gram Negative (-) Bacterial Keratitis Pseudomonas Gram (-) bacilli. Still grows on blood agar. Aerobic- facultatively anerobic. Infection more often associated with CL, surgery and/or trauma Ability to survive in the lens, storage case & eye Surrounding stroma= ground glass appearance Large arsenal of virulence factors: Pseudomonas aeruginosa antibiotic resistance Resistance genes, proteases (breakdown cornea), Topical FQ’s well tolerated, but.... increasingly resistant to FQ exotoxins, forms biofilms to protect itself monotherapy (2/2 its widespread use) Stromal necrosis & adherent mucopurulent exudate Along with S. aureus, Methicillin sensitive Staph. aureus, Greenish-yellow pus discharge Strep. Species Most common cause of CL related K infection 4th gen FQs (e.g. moxi, gati, besi)= expanded antimicrobial Trauma with contaminated water, soil, and/or spectrum to combat resistant strains, but.... MRSA and some vegetation exposure pseudomonas strains resistant to 4th gen Resistant to antibiotics→ Intrinsic and acquired mechanisms Very common in Southern US & in hospitals Gram negative bacilli Gram Negative (-) Bacterial Keratitis Contact lens wearers Serratia Marcescens Temperate>>tropical areas  Post-trauma or surgery Atypical Mycobacterium (non-TB) Contaminated sharp instruments Acid fast + bacteria Knife, blade relatively fast growing Vs slow growing M. sutures tuberculosis Most common: Slowly progressive keratitis Mycobacterium fortuitum Margins have spoke like or Frosted glass appearance Mycobacterium chelonae Diagnosis: Acid-fast stain Culture on Löwenstein-Jensen medium Suspect if lack of response to conventional antibiotic therapy Submitting lone CTA for mycobacteria testing without previously notifying lab will result in delay→ likely false negative Nocardia Indolent (slow) course Waxes and wanes Minor trauma Topical Amikacin= current standard of care for Nocardia keratitis Nocardia in S. Florida Exposure to contaminated soil Aminoglycoside CL wear = major risk factor in S. Florida Decaying vegetable matter, aquatic environments Active against many gentamycin and tobramycin resistant strains of Gram (-) bacilli 6 x more likely than trauma Raised, superficial, pinhead like infiltrates 64% (16/25) of all Nocardia isolates were resistant Wreath like config. 100% susceptible to either sulfamethoxazole-trimethoprim or linezolid (compounded for topical) Brush fire like border with multifocal lesions May simulate fungal keratitis Besifloxacin Antibiotic Choice Initial therapy No systemic equivalent= ↓ resistance 2 choices for empiric therapy (empiric meaning based Empiric, broad spectrum topical antibiotics activity against Gr -, + (incl MRSA) on experience and observation, but not on the culture) Routine, small corneal ulcers: Safe, good [tear film] + [conj] FQ monotherapy: 4th gen inhibit DNA gyrase and Topical FQ monotherapy q30-60 min initially; taper MIC discs to test for sensitivity not routinely done topoisomerase IV accordingly Dual agents still commonly used Combo therapy of fortified antibiotics excellent penetration Cost? May not be very available Aminoglycosides (tobramycin & gentamicin)→ commercially available Excellent Gram – coverage; also active against Staph outcomes equivalent to combo therapy Recommended Fortified Antibiotic Combo for Bacterial Keratitis while awaiting culture results/antibiotic susceptibility testing and some Strep loading dose q5 min for 1st half hr prn severity Cefazolin 50 mg/mL + [Gentamycin OR Tobramcyin 14 mg/mL] Cephalosporin (cefazolin) OR vancomycin depending Initially q1h each (alternate every 30 min) round the clock Requires knowledge of compounding pharmacy to direct pt to Features suggesting positive response to antibiotic Antibiotic Administration Store in fridge therapy: Q30 or 60 min for first 48 hrs Discard Cefazolin if yellow discoloration develops or after 1 week ↓’d: Loading dose q5 min for 1st 30 min Stinging pain To overcome poor penetration of the drug into the corneal Toxic to K epi cells discharge stroma lid edema Therapy gradually tapered off based on clinical response Vancomycin conjunctival injection Typically decreased with re-epitheliziation Significant pain on instillation; toxicity to ocular surface AC rxn Should be reserved for cephalosporin resistant organisms stromal edema Cases of vancomycin resistant keratitis emerging stromal infiltrate density Increasing minimum inhibitory concentrations over time progressive stromal thinning methicillin-resistant S aureus (MRSA): Consolidation and sharper demarcation of infiltrate Vancomycin 50 mg/mL perimeter Glycopeptide antibiotic with Gram + (staph and strep) coverage re-epithelialization  re-epithelialization Oxazolidinone antibiotic 1st introduced in 2000 Antibiotic resistant Gram + infections Bacterial Keratitis Tx vancomycin-resistant Enterococcus faecalis (VRE) MRSA Inhibits bacterial protein synthesis Low rate of resistance development over time Topical corticosteroid use in Bacterial Keratitis Controversial- why? Slows wound healing, can help microbes proliferate Steroids for Corneal Ulcers (SCUT) trial 500 pts with culture (+) bacterial K ulcers ≥ 48 hours of topical moxifloxacin q1h (awake) Randomized to pred phosphate 1% or sodium chloride 0.9% placebo Q.I.D. x 1 week  B.I.D. x 1 week  Q.D. x 1 week Antibiotic continued q2h until re-epithelialization; 4x/day thereafter Corticosteroid use associated with 1 line BSCVA improvement at 12 months Including Pseudomonas invasive species Corticosteroids= worse outcomes in Nocardia ulcers? Larger scar size Erythromycin ung 1 of best tolerated, least toxic topicals Not indicated in G(-) bacterial keratitis Does not penetrate cell membrane penetration into K is suboptimal Relative lack of solubility and bioavailability Topical Cycloplegic Reduces discomfort Prevents pupillary block related to inflammation Pts will then be light sensitive Acute use: Atropine 1% QD or Cyclopentolate 1% BID-TID  Cicatricizing Conjunctivitis Condition Definition/ Characteristics/Eitiology Signs/Symptoms/ Manifestations Treatment Tx: PF AT’s q1-2h Antibiotic coverage?? If abrasion is >1-2mm or pt has risk factors. BCL Improves comfort/pain. W/ antibiotic and RTC 1-2 days Should heal within a few days to a week Corneal Abrasion When not? If the abrasion is from vegetative material Risk of recurrance Air Optix indicated for longest wear Acuvue Oasys is 2nd choice (approved for about 6 days) Cyclopentolate 1% in office drop Helps with pain and discomfort Should give a numbing drop before instillation Causes: Cicatricial pemphigoid (aka mucus membrane pemphigoid- MMP) Stevens-Johnson Syndrome Toxic epidermal necrolysis Rosacea Atopic Keratoconjunctivitis Sjogren Syndrome Progressive systemic sclerosis Sarcoidosis Cicatricial Conjunctivitis Trachoma Epidemic keratoconjunctivitis Diptheria conjunctivitis "Pseudopemphigoid" Graft vs Host disease Neisseria gonorrhea Adenovirus Pilocarpine Burns, mechanical trauma, radiation damage Pemphigus vulgaris Predominantly secondary to conditions inducing conjunctival scarring. Secondary Obstructive Cicatricial: Duct orifices dragged posteriorly into conjunctival tarsal Cicatrizing MGD Trachoma mucosa Ocular pemphigoid (MMP) Erythema Multiforme Atopy Loss of limbal palisades of vogt Limbus= barrier preventing migration of conj epi cells over K Causes: SJS Limbal Stem Cell Deficiency (LCSD) MMP Akali burns AKC >>>VKC Trachoma Graft vs Host CL wear  Auto-antibodies against basement membrane at epi- Poor prognosis Mucus Membrane Pemphigoid (MMP) subepi junction of mucus membranes→ Subepithelial scarring of mucosal surfaces & skin There are still many ophthalmologists [and optometrists] who have the mistaken belief that MMP affecting the conjunctiva can be treated Avg age of diagnosis = 65 yrs (symptoms typically with drops (steroid, vitamin A, cyclosporine) or with subconjunctival injections (steroid, mitomycin C). It may take the disease 10–30 years begin about 2 years before this) or more to reach end stage, with bilateral blindness as the result. Systemic immuno-supression is needed - refer out! BUT: conj involvement can occur 10-20 yrs earlier before other sites: MMP Testing Type 2 HS rxn (B cell antibodies) Conj Biopsy = gold standard Double Hit Hypothesis Obtained from superior conj near scar. Inferior is usually worse and we don't want to create more scarring there. Ocular MMP: Affects conj > oral/ nasal/ esophageal > Direct immunofluorescent microscopy anus/genitalia Pemphigus= histological DDx intra-epithelial blistering disease Auto-Abs against desmosomes connections  Stage 1 Foster Stage 2 Foster Stage 3 Chronic conjunctivitis Subepithelial fibrosis process has progressed & contracted Further forniceal foreshortening Subepithelial fibrosis Forniceal foreshortening (white arrow) Symblepharon formation + CSEF Foster Stage 4 Complete loss of fornices MMP Ankyloblepharon Foster Stages Adhesion of UL to LL Surface keratinization Frequent Epilation Bandage (soft) CL or Scleral CL Trichiasis & entropion occur d/t conjunctival Trichiasis Permanent destruction of lash follicle subepithelial fibrosis (CSEF) Associated with MMP E.g. cryotherapy; radiofrequency (Ellman unit) Distichiasis also frequent Entropion repair If OCP/MMP well-controlled. Will worsen if not well controlled first  Severe Dry Eye with MMP Dry Eye Tx for MMP Anti-inflammatory antibiotics for meibomitis E.g. 50 mg Doxycycline QD-BID p.o. ; Azithromycin p.o. Topical azithromycin gtts Autologous Serum or Octaplas Platelet rich plasma (PRP) Topical steroid E.g. PF compounded methylprednisolone 1% Topical cyclosporine Cequa (topical cyclosporine 0.09%) Erythromycin 5mg/g ung Or Vitamin A containing ointment Punctal plugs?? Maybe not considered such a great approach anymore. Can scar over the plugs. Medically necessary CL Loss of goblet cells Vitamin A Conj scarring= occlusion of main & accessory ↑’s conj mucin expression lacrimal ducts Promotes correct K and conj wound healing Aqueous deficiency ↓’s apoptosis & epithelial metaplasia/keratinization Cicatricial obstructive MGD Squamous metaplasia= non- keratinized stratified epithelial cell replaced by non-secretory cutaneous keratinocyte-like cells Systemic supplement? Not sure there is evidence for this unless the pt is Vit A deficient Topical suppl. in pt’s w/ severe DED All-trans retinoic acid ung from compounding pharmacy 20-50% Autologous Serum Tears (AST) Contains epidermal growth factors (EGF), Vit A (&C), albumin, fibronectin, lysozyme 30-100 mL blood draw (specify red cap tubes) compounding pharmacy → specify [serum] Platelet rich plasma eye gtts compared to serum tears: More growth factors No inflammatory cytokines 4-6 x/day x 3 months; repeat prn Steven Johnson Syndrome (SJS) Acute blistering disorder affecting skin & mucus membranes CD8 T cells At least 2 mucus membranes involved Assoc w/ certain HLA alleles conjunctiva & oropharynx most frequently E.g. Life threatening HLA-B*58:01→ allopurinol Dry Eye Tx for (chronic?) SJS (same as MMP) Etiology: HLA-B15:02*→ carbamazepine and phenytoin Anti-inflammatory antibiotics for meibomitis E.g. 50 mg Doxycycline QD-BID p.o. ; Azithromycin p.o. drugs>>infection>> idiopathic HLA-A*02:06:01→cold medicine Topical azithromycin gtts Autologous Serum or Octaplas Pathophys Platelet rich plasma (PRP) NK cells & CD 8+ T lymphocytes Topical steroid Interval of 4–28 days between initiation of med and Kill keratinocyte & mucosal cells E.g. PF compounded methylprednisolone 1% onset of SJS/TEN suggests association Skin sloughing, necrosis Topical cyclosporine Antibiotics= faster reaction onset vs antiepileptic Infiltrate into skin forming blisters Cequa (topical cyclosporine 0.09%) and allopurinol' Erythromycin 5mg/g ung Skin lesions Or Vitamin A containing ointment Drugs with a high risk to induce SJS/TEN: Nomenclature based on skin involvement Punctal plugs?? Could leave inflam mediators on the ocular surface Allopurinol SJS: 30% Sulfa drugs  Non-specific bilateral conjunctivitis (75%) Daily exams Punctate epithelial erosions Rinse eyes (saline) & stain with NaFl Hemorrhagic lid crusting Old tx= sweeping of fornices Papillary conjunctivitis Topical steroid? Catch 22 with the epithelial defect Sometimes precedes skin/mucosal lesions Grittiness, photophobia, epiphora, visual blur Acute SJS Ophthalmic Disease symblepharon ring = prevent conj from adhering Resolves in 2-8 weeks Iritis & panophthalmitis reported Why are amniotic membranes helpful? Anti scar, anti inflam, anti microbe Is a sutureless cryopreserved or dehydrated amniotic membrane enough? Won't help areas it can't cover Conjunctival hyperemia & sloughing → madarosis, symblepharon Sutured amniotic membrane transplant required within 1 week → sooner means better prognosis Corneal epithelial defect Treatment: Dry eye tx like described for MMP Additional considerations Trichiasis Management Cryotherapy for trichiasis. -80 F, Significant swelling and pain afterwards, can damage nearby structures Radiofrequency (Ellman) unit: coagulation setting for trichiasis tx Trichiasis & Distichiasis Tarsorrhaphy Abrade K = scarring, LCSD Partial or full (small opening for meds and monitoring). May also be used for persistent epithelial defect Cicatricial entropion & epidermalization of conjunctiva 1. Mucus membrane graft Mechanical trauma to oc. Surface 2. Limbal stem cell transplant Cicatricial MGD ^will discuss at end of oGVHD portion but will apply to both SJS and MMP as well Nasolacrimal Duct Obstruction (NLDO) Prose Lens Chronic SJS/TEN Scarring beginning acutely= progressive Prosthetic replacement of the ocular surface ecosystem Chronic Manifestations: Not our only option, but sometimes pts think it is because that's what ophthamologists use Lid margin keratinization Caveats Conjunctival scarring Front surface non wetting Corneal keratinization Posterior surface fogging Limbal stem cell deficiency Do not fit overly tight→ tight lens syndrome Many fit/Rx changes likely required Be very careful around symblepharon (don't want to rupture it) Mucus membrane graft (MMG) Lid margin keratinizatoin = blink related microtrauma to oc. surf. Tissue harvested from upper or lower lip Doesn't replace lost goblet cells, but does ↓ friction & ↑ lid closure Etiology= HSV 2 forms Minor- mouth erythema multiforme (EM) Major= ≥ 2 mucosa’s Skin lesions= extremities Eyes are less commonly involved historically w/ SJS/TENS continuous spectrum of vesiculobullous disease  Indications: Poor K healing/LCSD Poor candidates for Limbal stem cell transplants *Prognosis for SJS= worse than other pre-op indications Keratoprosthesis "Be able to recognize type and know indications"  Bone Marrow Transplant Acute GVHD Ocular Graft vs Host Disease (oGVHD) Hematopoietic Stem Cell Transplant Skin: erythematous, maculopapular eruption Allogenic also upper back, neck, ears Yellow barrier filter another individual Liver: ↑ bilirubin, alkaline phosphatase if placed in front of oculars: Human Leukocyte Antigen (HLA) matched GI tract: Cramping, diarrhea, esophageal narrowing absorbs reflected blue light donors Kodak wratten filter #12 or 15 =most popular Conjunctival (acute) oGVHD grading Useful for conj. Staining Indications for BMT: Stage I = hyperemia only Leukemia Stage II = serosanguineous discharge, chemosis, hyperemia Acute GVHD Tx: oral pred Lymphoma Stage III = Stage III conjunctival oGVHD- pseudomembranes Multiple Myeloma Stage IV = Near complete epi sloughing oGVHD Tx Myelodysplasia Combination therapy Aplastic Anemia Systemic Graft vs Host Dis. (Chronic) Topical steroid Hemoglobinopathies Systemic GVHD ↑ risk of ocular Topical cyclosporine (Restasis; Cequa) or lifitegrast (Xiidra) Immunodeficiency disorders Ocular signs can manifest 1st Topical tacrolimus (compounded) Congenital blood disorders GI tract = esophogeal web, strictures, or stenosis Azithromycin or doxycycline p.o. Lung = Bronchiolitis obliterans Erythromycin ung qhs Graft vs Host Disease Pathophysiology Muscles, joints, fascia = fascitis, stiffness Serum Tears or autologous platelet derived gtts Donor derived T cells recognize host antigens as platelet derived drops compared to serum tears foreign Chronic oGVHD More growth factors Attack host tissues Superior limbic keratoconjunctivitis No inflammatory cytokines Acute oGVHD: donor T cell activation→ target cell Trichiasis (cicatricial entropion → trichiasis also possible 4-6 x/day x 3 months; repeat prn apoptosis Conjunctiva subepithelial fibrosis Pooled Ig- eye drops (flebogamma) → under study → Ocular surface immunomodulation e ect similar to IVIG Hallmark histological finding SPK/PEE PF AT’s Chronic oGVHD: Contact lenses CD8+ and CD4+ T cells BCL B cells & auto-antibodies Scleral CL ↓Tregs Systemic Immunosuppression for GVHD? Chronic oGVHD Balancing act-why? Donor-derived immune cells attack periductal & Graft-versus-tumor effect. Don't want leukemia for example to come back. secretory apparatus of lacrimal system and Want to limit susceptibility to infection meibomian glands Manage side effect load can progress to Organ specific treatments ideal cicatrizing conjunctivitis E.g. limbal stem cell deficiency (LCSD) Topical corticosteroid cream→mild skin GVHD corneal perforation Corticosteroid inhalers→ chronic lung GVHD Topical steroids, cyclosporine, serum/platelet tears→ chronic oGVHD But, higher grade GVHD with multi-organ involvement: High dose systemic corticosteroids + tacrolimus OR cyclosporine GVHD steroid sparing systemic immune suppression options ruxolitinib (Jakafi)= (JAK inhibitor; p.o. admin) ↓’s pro-inflammatory cytokines ↓’s T cell proliferation ↑’s Tregs Only drug that is FDA approved for chronic GVHD Cyclosporine (calcineurin inhibitors in T cells, suppress IL-2 trans