Viral Conjunctivitis (Pharyngoconjunctival Fever & Epidemic Keratoconjunctivitis) A Pseudomembrane in EKC Severe Follicular Reaction SIGNS AND SYMPTOMS

Most viral infections produce a mild, self-limiting conjunctivitis, but some have the potential to produce severe, disabling visual difficulties. The two most common selflimiting forms of viral conjunctivitis are epidemic keratoconjunctivitis and pharyngoconjunctival fever. Pharyngoconjunc-tival fever (PCF) is characterized by fever, sore throat and follicular conjunctivitis. It may be unilateral or bilateral. It is caused regularly by adenovirus 3 and occasionally 4 or 7. Corneal infiltrates are rare. The disorder varies in severity but usually persists for four days to two weeks. While the virus is shed from the conjunctiva within 14 days, it remains in fecal matter for 30 days. Epidemic Keratoconjunctivitis (EKC) often presents as a bilateral, inferior, palpebral, follicular conjunctivitis, with epithelial and stromal keratitis. Subepithelial corneal infiltrates are much more common in EKC than in PCF and are typically concentrated in the central cornea. EKC is regularly caused by adenovirus types 8 and 19. The key clinical signs of both conditions include: conjunctival injection, tearing, serous discharge, edematous eyelids, pinpoint subconjunctival hemorrhages, pseudomembrane formation and palpable preauricular lymph nodes. In severe cases, conjunctival desiccation causes scarring and symblepharon formation (adherence of the bulbar and palpebral conjunctivas). Both conditions are highly contagious. Patients will usually report recent contact with someone who had either red eyes or an upper respiratory infection. Both forms tend to start in one eye, then spread to the other eye within a few days. In rare cases, the focal subconjunctival hemorrhages can evolve into acute hemorrhagic conjunctivitis. PATHOPHYSIOLOGY Viral conjunctival infections are thought to be caused by airborne respiratory droplets or direct transfer from ones fingers to the conjunctival surface of the eyelids. After an incubation period of five to 12 days, the disease enters the acute phase, causing watery discharge, conjunctival hyperemia and follicle formation. Lymphoid follicles are elevated, with avascular lesions ranging from 0.2 to 2mm in size. They have lymphoid germinal centers that have responded to an infectious agent. Adenovirus type 8 can proliferate in the corneal epithelial tissues, producing the characteristic keratitis and subepithelial infiltrates. This, along with the immune response to viral antigens, causes lymphocytes to collect in the shallow anterior stroma, just beneath the epithelium. Sometimes, a conjunctival membrane will form. These are made

up of fibrin and leukocytes, and in prolonged cases, of fibroblast and collagen deposits. Pseudomembranes are much easier to remove than true membranes. MANAGEMENT Because EKC and PCF are contagious and self-limiting, the primary treatment once again is patient education. Instruct patients to stay home from work or school until there is absolutely no discharge. Also instruct them not to share utensils, glasses, linens or wash cloths with others. Medical management can range from cold compresses and artificial tears to topical vasoconstrictors (e.g., naphazoline) and steroids (Vexol, Flarex, Pred Forte) two to four times daily. If a membrane is present, peel it off with a wet, cotton-tipped applicator or forceps. After removal, prescribe a topical antibiotic-steroid combination such as Tobradex or Maxitrol q.i.d. Anti-viral drugs such as Viroptic are ineffective against adenovirus. Recently, there has been a breakthrough in the management of adenoviral keratoconjunctivitis. Cidofovir (Vistide), an anti-viral drug used intravenously to treat cytomegalovirus retinitis, appears to be effective in adenoviral keratoconjunctivitis. The topical form creates a faulty viral DNA structure. Twice daily instillation is recommended. This topical anti-viral is also possibly effective against herpes simplex and zoster, and Epstein-Barr virus. CLINICAL PEARLS Keep your equipment, instruments and chair area meticulously clean to avoid contaminating your patients and staff. Most practitioners reserve topical steroidal therapy for severe cases (if the infection is on the visual axis and affecting acuity, for example), or recalcitrant cases. EKC infiltrates resolve without scarring the cornea. Tell patients to expect the symptoms to get worse for about seven to 10 days before getting better, and that the infection wont completely go away for three to six weeks. Remember to always taper steroids slowly as the condition recedes. Allergic Conjunctivitis &Vernal Keratoconjunctivitis (VKC) SIGNS AND SYMPTOMS Itching and conjunctival injection are the two hallmarks of an allergic reaction. Also definitive is a lack of palpable preauricular lymph nodes, since palpable preauricular nodes signify viral infection. The eyelids may be swollen and red, and you may also see papillae of the palpebral conjunctiva. In most cases, patients will report a history of seasonal or other allergies. Seasonal allergies typically produce a thin, watery discharge and do not involve the cornea. If the patient exhibits thick, ropy discharge with severe itching and corneal involvement, it is most likely VKC rather than a seasonal allergy. VKCs prevalence is higher in the warmer climates. Onset is typically between the ages of three and 25 years. Males are typically more affected than females.

The important clinical signs of VKC include large conjunctival papillae on the back of the superior tarsus, Horner-Trantas dots (gelatinous, white clumps of degenerated eosinophils at the superior limbus), areas of superficial punctate keratitis (SPK) and, in severe cases, well demarcated, sterile, superiorly located corneal shield ulcers. PATHOPHYSIOLOGY An allergic response is an unwarranted over-reaction of the bodys immune system to foreign substances known as allergens, which the body wrongly perceives as a potential threat. The response can be innate or acquired. The presence of an allergen on the conjunctiva initiates two simultaneous immune responses, one caused by the release of so-called pre-formed inflammatory mediators such as histamine from mast cells, and the other by the production of arachidonic acid and its conversion into so-called newlyformed mediators such as prostaglandins (see Tracing the Complex Path of Allergic Reactions, on next page). Pre-formed mediators are released immediately upon exposure; newly-formed mediators are delayed roughly eight to 24 hours. In mast cell degranulation, the allergen attracts and binds to an antibody known as immunoglobulin E (abbreviated as IgE), then adheres to mast cells and causes them to degranulate, like a key opening a lock. This discharges the pre-formed mediators. Their effects can be either direct, indirect or a combination of the two. Two important mediators released from mast cells, histamine and bradykinin, immediately begin to stimulate nerve endings called nociceptors, creating the sensation of itching. Both also increase vascular permeability and vasodilation; this causes the clinical signs of redness and conjunctival injection. Meanwhile, other mediators released from mast cells send out chemical signals that attract both red and white blood cells to the area. Once these cells arrive, they easily reach the conjunctival surface by moving through the dilated and highly permeable capillaries. The bodys other defense mechanism, referred to as the arachidonic acid cascade, produces three newly-formed inflammatory mediatorsprostaglandins, thromboxanes and leukotrieneswhich are collectively known as eicosanoids. Virtually all cells contain a phospholipid layer within their cell walls. Any disruption or threat signals the cell to convert phospholipids into arachidonic acid. When arachidonic acid interacts with two enzymes known as cyclooxygenase and lipoxygenase, it is metabolized into eicosanoids. An allergens presence initiates the arachidonic acid cascade both within conjunctival epithelial cells and also within mast cells as they degranulate. Much like histamine and bradykinin, prostaglandins directly stimulate nerve endings to produce sensations of itching and pain, and also increase vascular permeability and vasodilation. Leukotrienes primarily attract macrophages (white blood cells).

MANAGEMENT Management of both allergic conjunctivitis and VKC is primarily aimed at alleviating symptoms. The most effective but least practical treatment is to prevent exposure to the allergen. Since this is not usually possible, instruct patients to frequently use cold compresses, artificial tears and ointments to soothe, lubricate and wash away the allergens. Also recommend that patients use a topical decongestant such as naphazoline or phenylephrine as needed. These drugs cause vasoconstriction, retarding the release of the chemical mediators into the tissues from the blood stream. This reduces hyperemia, chemosis and other symptoms. Mast cell stabilizers such as Alomide and Crolom help prevent the onset of allergic reactions by blocking the adherence of the IgE-allergen compound to the mast cell. Treat patients with a history of recurrent seasonal allergies using a mast cell stabilizer q.i.d. for four weeks in advance of allergy season. Patanol (olopatadine 0.1%) combines mast cell stabilization with an antihistamine to offer therapy that is for both acute and chronic symptoms. The effects last eight hours, allowing for b.i.d. rather than q.i.d. dosing. In moderate to severe cases, recommend one or more of the following, used from two to four times per day as needed: a topical medication such as Patanol or Livostin, oral antihistamines such as Benadryl, or a topical non-steroidal anti-inflammatory drug (Acular, Voltaren or Profenal). In extremely symptomatic cases, use a topical steroid such as Vexol, Flarex or Alrex q.i.d. Only prostaglandins and thromboxanes are produced when cyclooxygenase interacts with arachidonic acid. Leukotrienes, by contrast, are produced from the break-down of arachidonic by lipoxygenase. This leads to an interesting distinction in anti-inflammatory treatment. Non-steroidal drugs prevent the formation of cyclooxygenase but not lipoxygenase, thus they have virtually no effect on the production of leukotrienes. As a result, non-steroidals are useful in reducing itching and conjunctival injection but not very helpful in ridding the eye of excess immune cells. But because steroids inhibit the production of arachidonic acid itself, they reduce the production of all three eicosanoids. This is why we must use steroids to treat any inflammatory conditions characterized by a build-up of immune cells, such as chalazia, uveitis or corneal infiltrates. VKC patients who present with shield ulcers also need aggressive cycloplegia (atropine 1%, homatropine 5% or scopolamine 0.25%, b.i.d.) and a topical antibiotic (Tobrex, Ciloxan Ocuflox or Polytrim) q4-6h. To reduce the interaction between the lid and cornea, provide a low-water content soft lens as a bandage lens. When the corneal lesion has re-epithelialized, begin topical steroid therapy. Newer anti-histamines, such as dual-action olopatadine hydrochloride 0.1% (Patanol) b.i.d. as well as emedastine difumarate 0.5% (Emadine) q.i.d. have been seen to be very effective. A recently developed steroid, loteprednol etabonate (Alrex) q.i.d. is specifically marketed for the management of allergic conjunctivitis. CLINICAL PEARLS

Educate patients with a history of seasonal allergic conjunctivitis about how to avoid exposure to substances that precipitate symptoms, and recommend prophylactic treatment with a mast cell stabilizer. If effective, maintain this therapy for the duration of the season. Follow-up with patients on non-steroidal medicines in one to two weeks after the start of therapy. See patients on topical steroids no later than one week after the start of therapy, and monitor their IOP routinely for the duration of the therapy. Re-examine patients treated for shield ulceration every one to three days. Mast cell degranulation only occurs in allergic reactions, but the arachidonic acid cascade occurs after any threatening event, such as bacterial infection, surgery or accidental trauma. Follow up with patients placed on topical medications after one week, with close monitoring thereafter. Bacterial Conjunctivitis SIGNS AND SYMPTOMS Patients with bacterial conjunctival infections present with injection of the bulbar conjunctiva, episcleral vessels and perhaps papillae of the palpebral conjunctiva. The infection often starts in one eye, then soon spreads to the other. There will be thick mucopurulent discharge, and patients usually say that their eyelids and eyelashes are matted shut upon awakening. There may be mild photophobia and discomfort, but usually no pain. Visual function is normal in most cases. PATHOPHYSIOLOGY The eye has a battery of defenses to prevent bacterial invasion. These include bacteriostatic lysozymes and immunoglobulins in the tear film, the shearing force of the blink, the immune system in general, and non-pathogenic bacteria that colonize the eye and compete against external organisms that try to enter. When any of these defense mechanisms break down, pathogenic bacterial infection is possible. Invading bacteria, and the exotoxins they produce, are considered foreign antigens. This induces an antigen-antibody immune reaction and subsequently causes inflammation. In a normal, healthy person the eye will fight to return to homeostasis, and the bacteria will eventually be eradicated. However, an extra heavy load of external organisms can be too difficult to fight off, causing a conjunctival infection and setting the eye up for potential corneal infection. The most commonly encountered organisms are Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa. In cases of hyperacute bacterial conjunctivitis, the patient will present with similar signs and symptoms, albeit much more severe. The most common infectious organisms in hyperacute conjunctivitis are Neisseria gonorrhoeae and Corynebacterium diptheroides. There is more danger in hyperacute bacterial conjunctivitis as these organisms can penetrate an intact cornea.

MANAGEMENT Ordering cultures and sensitivity tests is ideal for diagnosis but usually impractical and expensive. Most clinicians immediately begin treatment with a broad spectrum antibiotic and reserve culturing for hyperacute conditions or those that fail to respond to the initial therapy. There are many antibacterial options. Excellent initial broad spectrum antibiotics include Polytrim (polymixin B sulfate and trimethoprim sulfate), gentamicin 0.3%, and tobramycin 0.3%. These will give good coverage of gram-positive and gram-negative organisms, though the aminoglycosides (gentamicin and tobramycin) have weak activity against Staphylococcal species; there are also resistant strains of Pseudomonas. Fluoroquinolones such as Ciloxan, Ocuflox and Chibroxin are also excellent options. Therapy should be aggressive, with administration from QID to Q1H for the first few days. Although antibiotics will eradicate the bacteria, they will do nothing to suppress the concurrent inflammation. If there is no significant corneal disruption, prescribe a steroid such as Pred Forte, Vexol or Flarex along with your antibiotic of choice, or a steroidantibiotic combination such as Maxitrol (neomycin, polymyxin B, dexamethasone 0.1%), Pred-G (gentamicin 0.3%, prednisolone acetate 0.1%), or Tobradex (tobramycin 0.3%, dexamethasone 0.1%). CLINICAL PEARLS Like patients with bacterial conjunctivitis, those suffering from viral and allergic conjunctivitis will often report that their lids are matted shut in the morning with mucopurulent material. However, these patients actually have crusting of the lashes due to drying of tears and serous secretions, not the wet, sticky, mucopurulent matting characteristic of bacterial conjunctivitis. Too often, clinicians will consider the crusting of the lashes to be the same as the mucopurulent matting and misdiagnose the condition. Remember, due to the excellent defense systems of the eye, acute bacterial conjunctivitis is uncommon. Chlamydial & Gonococcal Conjunctivitis SIGNS AND SYMPTOMS Chlamydial (inclusion) conjunctivitis typically affects sexually active teens and young adults and is the most frequent infectious cause of neonatal conjunctivitis in the U.S. The Centers for Disease Control (CDC) recognizes chlamydia as one of the major sexually transmitted pathogens, estimating approximately three million new cases per year. Women seem to be more susceptible than men. The incidence of infection seems to be directly related to sexual activity and geography, with urban populations having higher incidences. The incidence in pregnant women overall is 4 to 10 percent. Diagnosis of inclusion conjunctivitis is often difficult. Many times there are little, if any, symptoms. Infants whose mothers have untreated chlamydial infection have a 30 to 40

percent chance of developing neonatal chlamydial conjunctivitis. Systemic signs and symptoms may include a history of vaginitis, pelvic inflammatory disease or urethritis. Ocular signs and symptoms include the chief complaint that an eye infection has persisted for over three weeks despite treatment with topical antibiotics. Conjunctival injection, superficial punctate keratitis, superior corneal pannus, peripheral subepithelial infiltrates, iritis and follicles (most dense in the inferior cul-de-sac) may all be present. Mucopurulent, stringy or mucus discharge is common. A palpable preauricular node is almost always present. Gonococcal conjunctivitis, sometimes referred to as hyperacute conjunctivitis, is also a sexually transmitted ocular disease. While sexual contact is the customary route of transmission, even casual interaction with infected individuals has been reported as a cause. Newborn infants may acquire the infection by passing through an infected birth canal. Systemically, gonococcal infections are associated with infection of the urethra, cervix and rectum. Symptoms vary from nothing to discharge and irritation. This unusually contagious ocular disease typically presents as a hyperacute red eye of less than four weeks duration with foreign body sensation; the eye may be glued shut with severe purulent discharge. The conjunctivitis has an incubation period of two to seven days. Conjunctival papillae, superficial punctate keratitis and marked chemosis are almost always present. Subconjunctival hemorrhage (hemorrhagic conjunctivitis), pseudomembrane or true membrane formation and preauricular lymph nodes are usually present. In chronic, recalcitrant or severe cases, peripheral subepithelial corneal infiltrates may occur, leading to marginal ulceration with anterior uveitis. PATHOPHYSIOLOGY Chlamydia trachomatis is an intracellular parasite that contains its own DNA and RNA. The sub-group A causes chlamydial infections, the serotypes A, B, Ba and C cause trachoma, and serotypes D through K produce adult inclusion conjunctivitis. The mode of ocular transmission may be hand contact from a site of genital infection to the eye, laboratory accidents, a mother infecting the newborn, shared cosmetics and occasionally an improperly chlorinated hot tub. Diagnostic testing for chlamydia is expensive and difficult to interpret. The preferred method of identification is to culture the organism. Conjunctival scrapings for Giemsa staining will show intracytoplasmic inclusion bodies in epithelial cells, polymorphonuclear leukocytes and lymphocytes. The infectious organism in gonococcal conjunctivitis is Neisseria gonorrhoeae, a gramnegative, intracellular diplococcus capable of invading an intact mucosal membrane. Transmission is generally by direct or indirect sexual contact or contact with an infected individual. N. gonorrhoeaes ability to penetrate an intact corneal epithelium makes the risk of corneal infection and ulceration high. MANAGEMENT

In treating chlamydial conjunctivitis, many doctors consider oral tetracycline 250 to 500mg q.i.d. for three weeks the treatment of first choice. But since tetracycline must be administered one hour before or after meals to avoid gastrointestinal side effects and interference of dairy products with its efficacy, other oral medications may be more appropriate. Amoxacillin and erythromycin 250 to 500mg q.i.d. for three weeks or doxycycline 100mg b.i.d. for one week are acceptable alternatives. Currently, the drug of choice is azithromycin (Zithromax). Taken as a 1 gram dose, by mouth, one time, it has been documented as being as effective for the treatment of genital chlamydial infection as doxycycline. Topical therapy is adjunctive and includes erythromicin, tetracycline or sulfacetamide t.i.d. for three weeks as well. Patients with gonococcal conjunctivitis require immediate conjunctival scrapings for culture and sensitivity testing. Medical management of gonococcal infection begins with an intramuscular loading dose of ceftriaxone 1g. Ideally, the patient should be hospitalized and given one gram of ceftriaxone intravenously within 12 to 24 hours. Following discharge, resume treatment with either erythromicin 250 to 500mg p.o. q.i.d., tetracycline 250 to 500mg p.o. q.i.d. or doxycycline 100mg p.o. b.i.d. Begin ocular management with saline lavage to clear the mucopurulent debris from the lids and conjunctiva. A topical fluoroquinolone (ofloxacin or ciprofloxacin) is appropriate if corneal infection occurs. However, because gonococcal conjunctivitis does not respond to topical antibiotics, topical therapy is usually not indicated. CLINICAL PEARLS Inclusion conjunctivitis should be one of the differential diagnoses any time a patient presents with a chief complaint of chronically red eyes or follicular conjunctivitis that is recalcitrant to topical therapies. Follow up should be weekly. Educate patients that the disease is contagious and that partners are at risk and should be examined. Follow up with gonococcal conjunctivitis patients every day until you see consistent improvement. Educate the patients regarding the circumstances surrounding the disease and that partners at risk should be informed about the possibility of infection. Finally, contact the Centers for Disease Control for instructions and recommendations. Conjunctival Laceration SIGNS AND SYMPTOMS Because the conjunctiva is far less innervated than the cornea, conjunctival abrasions and lacerations are less symptomatic than corneal abrasions of the same severity. Patients will present with a history of ocular trauma and complain of mild pain or a scratchy, foreignbody sensation in the affected eye. There may be some tearing and photophobia; vision is rarely impaired. The adjacent vessels will be dilated, and there will often be a subconjunctival hemorrhage. With the slit lamp, the affected region of the conjunctiva will appear torn and the edges may be retracted, revealing the underlying sclera. Fluorescein will pool in the area of the laceration under the cobalt filter. Eventually, stain will seep underneath the conjunctiva and produce a generalized "glow" to that part of the

eye. Be careful to differentiate this pattern of staining from simple accumulation of fluorescein within the physiologic folds of the conjunctiva. PATHOPHYSIOLOGY Although the conjunctiva is normally a tough, resilient tissue, it may be lacerated in cases of ocular trauma with sharp or pointed objects such as fingernails, tree branches or the edge of a piece of paper. In these cases, the trauma itself acts as an antigen and sets off an inflammatory cascade resulting in vasodilation and edema of the involved and surrounding tissues. Rarely is there significant white cell proliferation to the point of causing an anterior chamber reaction. MANAGEMENT As with any case of ocular trauma, it is important to rule out global perforation. We recommend using the Seidel test, in which you apply fluorescein to the laceration and look carefully for external leakage of aqueous. Also meticulously inspect the surrounding area to look for subconjunctival foreign bodies. Once you are certain that there are no perforations or other complications, begin treatment. If the involved area of conjunctiva is small, use a broad spectrum antibiotic (Polytrim solution Q3-4H, gentamicin solution or ointment QID, or Polysporin ointment QID) and examine the patient again in three to five days. Patching is generally not necessary for smaller lesions. If the laceration is larger, first apply topical anesthesia and use a forceps or moistened cotton-tipped applicator to manipulate any ragged areas of conjunctiva back into position. Then instill an antibiotic ointment and pressure-patch the eye for 24 hours. While most conjunctival lacerations resolve without surgical repair, significantly large (i.e., greater than 2cm) wounds may require suturing. This should only be performed by a qualified optometrist or ophthalmologist. CLINICAL PEARLS Conjunctival lacerations are a minor problem that typically resolve with minimal intervention, yet patients often present with great anxiety. The fact that the eye is very red and often hemorrhaging may be cause for great concern on the patient's part, even though there is little pain or other symptoms. While it's important to rule out a penetrating injury, you can safely reassure most patients that they have a simple "cut" on their eye, and that it will heal in a few days.