Ocular therapeutics - Part 15

MICROBIAL KERATITIS
Microbial keratitis can result from a broad spectrum of pathogens (bacteria, viruses, fungi and amoebae) which give rise to a diverse range of host responses. Microbial keratitis is a sight-threatening disease that requires prompt diagnosis and treatment.

Bacterial keratitis
Bacterial keratitis rarely occurs in the normal eye because of the cornea's natural resistance to infection. However, predisposing factors including contact lens wear, trauma, corneal surgery, ocular surface disease, including tear deficiencies, systemic diseases and immunosuppression may alter the defence mechanisms of the ocular surface and permit bacteria to invade the cornea.
Corneal ulceration, stromal abscess formation, surrounding corneal oedema and anterior segment inflammation are characteristic of bacterial keratitis. The most common groups of bacteria responsible include: Streptococcus, Pseudomonas, Enterobacteriaceae (including Klebsiella, Enterobacter, Serratia and Proteus), and Staphylococcus species.
Patients with bacterial keratitis usually complain of rapid onset of pain, profuse tearing, photophobia, and decreased vision. There will often be a focal stromal infiltrate with an overlying area of epithelial excavation. There may also be associated conjunctival hyperaemia, anterior chamber reaction with or without hypopyon, folds in Descemet's membrane and upper eyelid oedema. The collagen of the corneal stroma is poorly tolerant of the bacterial and leukocyte-derived enzymes, and undergoes degradation, necrosis and thinning (see optician, September 24, 2004, Part 9). This leads to scarring of the cornea. As thinning advances, the cornea may perforate, thus introducing bacteria into the eye with ensuing endophthalmitis.
Cases of suspected bacterial keratitis should be sent immediately to the hospital eye service (contact lens wearers should be instructed to take their lenses and case with them for culture). Corneal scraping from the base and margins of an ulcer is always indicated whenever bacterial keratitis is suspected. It not only provides material for a microbiological diagnosis and sensitivity, but also debrides necrotic tissue and enhances antibiotic penetration.
If the corneal ulcer is small, peripheral and no impending perforation is present, intensive monotherapy with topical fluoroquinolones may be effective. If the ulcer is more severe, hourly broad-spectrum antibiotics such as cefuroxime and gentamycin may be indicated. Strong cycloplegia is also mandatory in order to increase patient comfort and minimise inflammation. The patient should be followed daily until the infection is well controlled. If the results of cultures and sensitivities show that the initially prescribed antibiotic is appropriate for the infective organism, while steroids have historically been avoided in the management of infectious keratitis, judicious use can be beneficial. Antibiotics can suppress the infective organism, while corticosteroids can inhibit the corneotoxic inflammatory response. Steroids should not be employed until the antibiotic has been given enough time to sterilise the ulcer, minimally 24 hours. One also must be certain that there is not a simplex viral, fungal, or protozoan infection prior to the initiation of topical steroids.
Marginal keratitis is associated with staphylococcal lid disease, and patients exhibit, as well as signs of chronic blepharitis (see optician, March 25, 2005, Part 14), marginal infiltrates. These are small focal white cell infiltrates in the corneal stroma, usually adjacent to the limbus, but with a clear margin between the ulcer and the limbus. There is associated adjacent conjunctival injection, and the epithelium over the ulcer may be intact or may stain slightly with fluorescein. This immune-mediated keratitis responds to topical steroid, and most patients are also given broad-spectrum antibiotic to reduce the bacterial load. The main differential diagnosis is acute microbial keratitis, and if in doubt the patient may need referral. However, patients with multiple small ulcers, or a previous history of marginal keratitis, or where the diagnosis is certain, may be managed to resolution by their optometrist.

Viral keratitis
Virus particles are able to cause disease, even in the presence of a healthy intact corneal epithelium. The common causative organisms are Herpes simplex, Herpes zoster, Epstein Barr, cytomegalovirus and adenovirus.

Herpes simplex keratitis
Herpes simplex is a DNA virus with humans as the only host. Infection is spread by direct contact of infectious secretions with epidermis or mucous membrane. Herpes simplex virus type 1 (HSV-1) is primarily responsible for orofacial and ocular infections, and HSV type 2 (HSV-2) generally is transmitted sexually and causes genital infections. Very occasionally HSV-2 may be transmitted to the eye from infected genital secretions. Primary infections occur most often in children between the ages of six months and five years. It typically manifests as a vesicular rash, sometimes affecting the skin of the lids but more commonly resulting in a 'fever blister' or 'cold sore' in or around the mouth, and a follicular blepharoconjunctivitis. After resolution, the virus remains dormant in the nerves in the body of the host and can be reactivated in as many as 25 per cent of cases by fever, trauma, stress, immunosuppressive agents or exposure to ultraviolet radiation.
In recurrent HSK, the virus invades and replicates within the corneal epithelium. Ocular HSV tends to be a unilateral disease with only one eye affected by the primary disease in 80-90 per cent of cases. The keratitis caused by the herpes simplex virus typically presents as a unilateral 'red eye' with a variable degree of pain or ocular irritation. Photophobia and epiphora are common; however, vision may or may not be affected, depending upon the location and extent of the corneal lesion. There may be a secondary uveitis. A history of prior episodes in patients with recurrent disease may exist. A dendritic corneal ulcer is the hallmark sign of HSV infection (Figure 1), accompanied by stromal keratitis in more severe presentations. These ulcers may begin as nondescript punctate keratopathies, but quickly coalesce to form the familiar branching patterns, which stain brightly with sodium fluorescein dye. Because the virus invades and compromises the epithelial cells surrounding the ulcer, the leading edges (the so-called 'terminal end-bulbs') will stain with rose bengal (or lissamine green). Most cases of HSV epithelial keratitis resolve spontaneously within three weeks, the rationale for treatment is to minimise stromal damage and scarring, and to ease symptoms. Corneal epithelial disease secondary to HSV infection must be managed aggressively and quickly to prevent deeper penetration. Treatment is with topical antivirals: aciclovir or ganciclovir drops. Some authors advocate gentle epithelial debridement to remove infectious virus and viral antigens that may induce stromal keratitis.
Herpes zoster ophthalmicus (HZO) is an infection caused by the varicella-zoster virus (VZV). VZV is a member of the Herpes viridae family. It is the aetiologic agent of varicella (chickenpox), the primary infection, and Herpes zoster, the reactivation. After primary infection, VZV enters the dorsal root ganglia (trigeminal) where it remains latent for the lifetime of the individual. Although the exact precipitants that result in viral reactivation are not known for certain, decreased cellular immunity appears to increase the risk of reactivation. Immunocompromised individuals with decreased cell-mediated immunity from HIV, carcinoma, chemotherapy, or radiation therapy are at greater risk of reactivation of latent VZV than immunocompetent individuals. Approximately 90 per cent of the adult population is seropositive for VZV. By the age of 80 years, as many as 50 per cent of persons who have had chickenpox develop zoster. Herpes zoster ophthalmicus (HZO) typically presents with nondescript facial pain, fever and general malaise. About four days after onset, a vesicular skin rash appears along the distribution of the fifth cranial nerve, characteristically respecting the vertical midline. Patients may also experience eye pain, red eye (usually unilateral), decreased vision, and tearing. The vesicles will discharge fluid and begin to scab over after about one week. The pain is extreme during the inflammatory stage, and patients are tremendously symptomatic.
Ocular involvement may include follicular conjunctivitis, epithelial and/or interstitial keratitis, dendritic keratitis, hypertensive uveitis, scleritis or episcleritis, chorioretinitis, optic neuropathy, and even neurogenic motility disorders (especially a fourth cranial nerve (trochlear) palsy). If vesicles are present at the tip of the nose (known as Hutchinson's sign), there is a 75 per cent likelihood of ocular sequelae. Goals of therapy in herpes zoster infection are to (1) shorten the clinical course, (2) provide analgesia, (3) prevent complications, and (4) decrease incidence of post-herpetic neuralgia. Antivirals prevent replication of viral particles. These medications are important to use in treating Herpes zoster and should be started within 72 hours of onset for maximal effectiveness. Acyclovir is the agent that has been used most widely. Newer agents (eg famciclovir, valaciclovir) may be more effective and have more convenient dosing. Topical steroids may be used later on to reduce inflammation, but are often needed for months or years. Oral analgesia is often required for the control of pain from facial lesions as is cycloplegia for ocular pain.

Acanthamoeba keratitis
Acanthamoeba species are free-living protozoa, found in air, soil and water. They exist in two forms, trophozoite (active) and cystic (dormant) forms. The cystic form is highly resilient, and can survive in chlorinated pools, hot tubs and frozen lakes. Acanthamoeba infection occurs after damage to the corneal epithelium such as a corneal abrasion. The trophozoite form releases enzymes that aid tissue penetration and destruction. Soft contact lens wearers are at particular risk. Contamination of contact lens care systems is often the source of infection <2212> most commonly reported in patients using tap water to clean their lenses. Acanthamoeba may also co-exist with other pathogens such as herpes simplex. Patients present with blurred vision and severe ocular pain disproportionate to ocular findings. Examination reveals limbitis, patchy anterior stromal and perineural infiltrates. The epithelium may be intact or manifest punctate epitheliopathy or pseudodendritic keratitis. The infiltrates may gradually coalesce to form a central ring abscess. Differential diagnoses include herpetic and fungal keratitis. Treatment is topical amoebicides (chlorhexidine, propamidine isetionate and polyhexamethylene biguanide), topical steroids to reduce inflammation and severe cases may need a corneal graft to preserve the globe or for persistent stromal opacity.

CONJUNCTIVITIS
Conjunctivitis is defined as an inflammatory process involving the conjunctiva. It is often classified according to its more common causes into bacterial, viral and allergic. Other more rare causes include fungal, parasitic, toxic, and chemical. The cause of conjunctivitis is usually a clinical diagnosis - occasionally swabs may be required to identify pathogens and check sensitivity to chosen treatment in severe or non-responsive cases. Cellular infiltration and exudation characterise conjunctivitis on a cellular level. The symptoms of conjunctivitis are dependant on the cause.

Bacterial conjunctivitis
The surface tissues of the eye and the ocular adnexa are colonised by normal flora such as Streptococci, Staphylococci, and Corynebacterium strains. Alterations in the host defence or in the species of bacteria can lead to clinical infection. An alteration in the flora can occur by external contamination, by spread from adjacent sites, or via a blood-borne pathway. The primary defence against infection is the epithelial layer covering the conjunctiva. Disruption of this barrier can lead to infection. Secondary defences include haematologic immune mechanisms carried by the conjunctival vasculature; tear film immunoglobulin and lysozyme; and the rinsing action of lacrimation and blinking. Bacterial conjunctivitis is common worldwide. Age is a relevant factor in the significance of bacterial conjunctivitis. Patients at a sexually active age should be considered for sexually-transmitted diseases caused by Neisseria gonorrhoeae and Chlamydia as well as in newborns that may have been exposed during birth.
Patients with bacterial conjunctivitis complain of an acute onset of conjunctival hyperaemia, purulent discharge (Figure 2), ocular irritation, and eyelids that are stuck together on awakening. Pain is rarely a symptom, though the eye may feel sore or gritty. Symptoms are more often unilateral. There may also be moderate lid swelling. Ocular surface disease (eg, keratitis sicca, trichiasis, chronic blepharitis) predisposes the patient to bacterial conjunctivitis. Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae are common causes of bacterial conjunctivitis. The mainstay of medical treatment for bacterial conjunctivitis is topical antibiotic therapy. Systemic antibiotics are indicated for N gonorrhoeae and chlamydial infections. Practice patterns for prescribing topical antibiotics vary. Most practitioners prescribe a broad-spectrum agent (eg chloramphenicol) on an empirical basis without culture, for a routine, mild-to-moderate case of bacterial conjunctivitis. Most patients require a 4X per day (qds) regime for around five days, but severe cases may need the topical antibiotic two-hourly to start.

Viral conjunctivitis
A variety of viruses can be responsible for conjunctival infection; however, adenovirus is the most common cause. Most viral infections produce a mild, self-limiting conjunctivitis, but some have the potential to produce severe, disabling visual difficulties. Viral conjunctivitis is highly contagious. Patients will usually report recent contact with someone who had either red eyes or an upper respiratory tract infection. Both forms tend to start in one eye, and then spread to the other eye within a few days. Symptoms include moderate to marked conjunctival hyperaemia, watery discharge, ocular irritation and itching. Occasionally, severe photophobia and foreign-body sensation occurs, usually caused by adenovirus (epidemic keratoconjunctivitis [EKC]), when associated with keratitis. Pre-auricular lymph nodes are commonly involved, and are often swollen and tender. If follicles are present on the palpebral conjunctiva in conjunction with lymphadenopathy, then EKC is the most likely diagnosis. Herpes simplex and chlamydia may also cause follicular conjunctivitis and pre-auricular adenopathy. EKC may be associated with a keratitis, in which small round (coin-like or 'nummular') subepithelial infiltrates are seen. These are probably immune-mediated, and may persist for months or years. These corneal changes will occasionally result in decreased vision and significant glare, and respond to topical steroids, but it is often difficult to subsequently withdraw the steroid without recurrence. Most cases of viral keratitis are self-limiting (within two to three weeks). Patients should be advised of the highly contagious nature of the condition and practitioners should apply appropriate aseptic technique during and after examination to prevent cross-infection. Anti-viral drugs are ineffective, although tear supplements and unmedicated ointment at night may give symptomatic relief. Patients should be reviewed to monitor for corneal signs. Referral is indicated in severe cases, particularly those with corneal involvement.
Allergic conjunctivitis
Pruritis (itching) and chemosis of the conjunctiva and lids are the hallmark signs and symptoms of this form of conjunctivitis. The eyes are usually bilaterally affected, discharge may also be present, but is sparse to moderate, ropy and clear. It is usually acute in onset with the precipitant unknown. This conjunctivitis is due to a Type I anaphylactic hypersensitivity reaction to a specific antigen (allergen) usually airborne pollen of trees or grasses (see Part 8). The first stage in the sensitisation of mast cells is the production of an allergen-specific IgE response, following the initial exposure to the allergen. The IgE then binds to specific receptors on the surface of mast cells. Subsequent cross-linking of these IgE molecules by the same allergen causes mast-cell degranulation. This discharges the pre-formed mediators. 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 and this causes the clinical signs of redness and conjunctival injection. Other mediators released from mast cells send out chemical signals that attract 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.
A second wave of mediators are synthesised from plasma membrane phospholipids via arachidonic acid. An allergen's presence initiates the 'arachidonic acid cascade' both within conjunctival epithelial cells and also within mast cells as they degranulate. The arachidonic acid cascade, produces three newly-formed inflammatory mediators; prostaglandins, thromboxanes and leukotriene. Prostaglandins directly stimulate nerve endings to produce sensations of itching and pain, and with thromboxane also increase vascular permeability and vasodilation. Leukotrienes primarily attract macrophages.
Allergic conjunctivitis may be divided into five major subcategories:

Seasonal allergic conjunctivitis (SAC)
Perennial allergic conjunctivitis (PAC)
Vernal keratoconjunctivitis (VKC)
Atopic keratoconjunctivitis (AKC)
Giant papillary conjunctivitis (GPC).

Seasonal allergic conjunctivitis and perennial allergic conjunctivitis are often grouped together differing mainly in the time of occurrence. SAC occurs mainly in spring and summer, while perennial occurs throughout the year. In SAC, tree and grass pollens are thought to be the main antigens stimulating the hypersensitivity response. In PAC, though pollen may also be implicated, household allergens such as dust mite and pet dander may also trigger the conjunctival reaction. The allergens that trigger allergic rhinitis may be involved in the pathogenesis of allergic conjunctivitis given the similarities in nasal and conjunctival mucosa. The symptoms the patient experiences are those of acute allergic conjunctivitis such as ocular itching, redness, burning, and tearing. A personal or family history of atopic disease, such as allergic rhinitis, bronchial asthma, and/or atopic dermatitis (eczema) is often present. Classic signs of allergic conjunctivitis include injection of conjunctival vessels as well as varying degrees of chemosis and eyelid oedema. Treatment is with topical antihistamines (eg antazoline, levocabastine) for rapid relief (in conjunction with oral antihistamines where there is an associated rhinitis).
Topical mast-cell stabilisers such as sodium cromoglicate or lodoxamide are valuable for long-term control. Newer anti-histamines, such as olopatadine (Opatanol), combine mast cell stabilising properties with histamine-receptor blockade to offer therapy that is for both acute and chronic symptoms.
Vernal keratoconjunctivitis is a recurrent chronic bilateral inflammatory condition typically affecting children and young adults (males more than females). More than three quarters of these patients have associated atopic disease and two thirds, a close family history of atopy. Most children outgrow the condition by early adulthood. VKC may be subdivided into two varieties - palpebral and limbal. Itching is the most common symptom, although patients may also experience photophobia, foreign body sensation, tearing, and blepharospasm. The important clinical sign of palpebral VKC is giant papillae on the superior tarsal conjunctiva. These papillae give the conjunctiva a cobblestone appearance (Figure 3). A ropy mucous discharge is often present. Horner-Trantas dots (gelatinous, white clumps of degenerated eosinophils at the superior limbus) are characteristic of limbal VKC. Limbal VKC is more common in black patients and is the less severe of the two forms. Both forms of VKC are often accompanied by corneal changes such as superficial punctate erosions (SPE), macroerosions, plaque and, in severe cases, well demarcated, sterile, superiorly located corneal shield ulcers. Sub-epithelial scarring may occur at sites of previous ulcers. Treatment options (generally under ophthalmologists' control) include topical steroids, mast cell stabilisers (especially useful for weaning patients off topical steroids) and the mucolytic, acetylcysteine.
Atopic keratoconjunctivitis (AKC) is associated with a 95 per cent prevalence of concomitant eczema and an 87 per cent prevalence of asthma. Atopy refers to hypersensitivity in patients with familial histories of allergic disease. Individuals with atopy often have environmental allergies, allergic asthma, rhinitis, and atopic dermatitis or eczema. Immunoglobulin E (IgE) is the serum mediator of the exuberant responses.
AKC may affect eyelid skin and lid margin, conjunctiva, cornea, and lens. Skin of the eyelids may exhibit eczematoid dermatitis with dry, scaly, and inflamed skin. Lid margins may show meibomian gland dysfunction and keratinisation. Staphylococcal colonisation of eyelid margins is very common and may result in blepharitis. The conjunctiva may show chemosis and typically a papillary reaction, which is more prominent in the inferior tarsal conjunctiva, in contrast to that seen in vernal keratoconjunctivitis. Untreated, AKC can progress to ulceration, scarring, cataracts, keratoconus, and corneal vascularisation. Conjunctival biopsy can help differentiate AKC from cicatricial pemphigoid by the presence of basement membrane antibodies or complement components in cicatricial pemphigoid. Although mild cases can be managed with mast-cell stabilisers, since topical steroids and other immunosuppressives (eg ciclosporine) are frequently required, AKC is most appropriately managed by an ophthalmologist.
Giant papillary conjunctivitis (GPC) is a common condition frequently seen in soft contact lens patients, patients with exposed suture knots, and patients with prostheses. Patients with asthma, hay fever or animal allergies may be at greater risk. The aetiology of GPC may be immunological, where contact lens deposits act as allergens. The initiating event is believed to be mechanical irritation of the tarsal conjunctiva of the upper lid(s), followed by histological changes in the tissue (mast-cell degranulation and the typical secondary inflammatory cascade). Poor fitting, poor cleaning, rough CL edges, and extended wearing times favour development of GPC. Rigorous cleaning (particularly with enzymes), peroxide disinfection, decreased wear times, using lens material of a lower modulus and increased rates of contact lens replacement (perhaps daily) appear to reduce the prevalence of GPC among soft contact lens users. Patients often report decreasing contact lens tolerance and mechanical stability, ocular itching, and mucous discharge in the tears, as well as blurred vision and conjunctival injection. With eversion of the lids, inflammation of the vasculature (hyperaemia) and papillary hypertrophy are noted. Mucous strands are seen both in the tears and between the papillae. Papillae can range from small, uniform lesions (uniform cobblestone appearance) to irregular changes (non-uniform cobblestone appearance) to clusters of giant lesions with whitish centres that can ulcerate and stain with sodium fluorescein dye. The GPC response has no seasonal variation. Management is primarily aimed at reducing symptoms. In more serious cases, aggressive management may be required to prevent ocular tissue damage. Topical supportive therapies (ie lubricants) act to supplement the biological tears, to wash away debris and environmental allergies. Once significant GPC is diagnosed, patients who wear contact lenses purely for cosmesis should discontinue contact lens wear for at least three to four weeks (the interval during which symptoms may begin to reverse and signs improve). When contact lens wear is resumed, try to dispense new contact lenses. Patients who wish to return to soft contact lenses should use peroxide disinfection systems or daily disposable soft lenses. Topical mast-cell stabilisers are a tested and proven modality for treating GPC. However, given that GPC is a non-sight threatening condition, it is difficult to justify the use of topical corticosteroids (except in the case of a prosthesis).

EPISCLERITIS
Episcleritis is an inflammatory condition affecting the episcleral tissue that lies between the conjunctiva and the sclera. Episcleritis is usually a mild, self-limiting, recurrent disease. Most cases are idiopathic; although up to one-third have an underlying systemic condition. Episcleritis occurs in young adults and affects women more often than men. Episcleritis presents as a relatively asymptomatic, acute-onset redness in one or both eyes. Some patients complain of mild pain or tenderness to the affected region. Typically, there is sectoral injection of the episcleral and overlying conjunctival vessels (Figure 4), although the redness may be diffuse throughout these tissues. A hyperaemic, oedematous, raised nodule may also be present (nodular episcleritis). The palpebral conjunctiva is normal. Patients with nodular episcleritis have prolonged attacks of inflammation that are typically more painful than simple episcleritis. Some patients with nodular episcleritis have an associated systemic disease, most notably systemic connective tissue disease (rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, seronegative spondyloarthropathies, such as ankylosing spondylitis, inflammatory bowel disease, Reiter syndrome, psoriatic arthritis) and gout. Differential diagnoses include viral conjunctivitis, scleritis and superior limbic keratoconjunctivitis.
Simple episcleritis often requires no treatment apart from reassurance to the patient. Artificial tears are useful for patients with mild-to-moderate symptoms. Patients with severe or prolonged episodes may require artificial tears and/or topical corticosteroids. Nodular episcleritis is more indolent and may require local corticosteroid drops or anti-inflammatory agents. Most patients with episcleritis can be managed to resolution by their optometrist. Further investigation is usually not required, as the condition does not cause ocular damage, and only if the patient has other symptoms are systemic investigations by their GP or rheumatologist needed.

SCLERITIS
Scleritis is a chronic, painful, and potentially blinding inflammatory disease that is characterised by oedema and cellular infiltration of the scleral and episcleral tissues. It is (in over 50 per cent of cases) associated with systemic disease. Among the most common related disorders are rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, polyarteritis nodosa, Wegener's granulomatosis, Herpes zoster virus, gout and syphilis. Scleritis is most common in the fourth to sixth decades and affects women more often than men. Scleritis may be classified into anterior and posterior. Anterior scleritis can subdivided into:

Diffuse - anterior scleritis is characterised by widespread inflammation of the anterior portion of the sclera. This is the most common form of anterior scleritis, as well as the most benign.
Nodular - erythematous, immovable, and tender, inflamed nodules on the anterior sclera characterise nodular anterior scleritis. Approximately 20 per cent of cases progress to necrotising scleritis.
Necrotising (with inflammation) - frequently accompanies serious systemic collagen vascular disorders, in particular Wegener's. Pain with this condition is usually extreme, and damage to the sclera is often marked.
Necrotising (without inflammation) - also known as scleromalacia perforans most frequently occurs in patients with long-standing rheumatoid arthritis and is notable for an absence of symptoms.
Posterior scleritis is characterised by flattening of the posterior aspect of the globe, thickening of the choroid and sclera, and retrobulbar oedema. It may extend into the anterior segment of the eye.

The immunology of scleritis has been described in optician (July 30, 2004, Part 8). Patients complain of a pain (most often characterised as a deep ache) so extreme that it often interferes with sleep and appetite. Pain may be referred to the eyebrow, temple, or jaw. Occasionally, the configuration of the pain pattern corresponds to the course of the trigeminal nerve. Patients also complain of tenderness, photophobia, lacrimation, and localised or generalised conjunctival hyperemia. Onset of scleritis is more gradual than is seen in episcleritis. Both eyes are affected in slightly over half of cases. Widespread injection of the conjunctival and deep episcleral/scleral vessels is characteristic of diffuse anterior scleritis. Localised elevation of the sclera is representative of nodular anterior scleritis. Nodules in anterior scleritis differ from those occurring in episcleritis, in that the nodule is immobile with scleritis. A black, grey, or brown area that is surrounded by active scleral inflammation indicates a necrotising process. If tissue necrosis progresses, the scleral area may become avascular, producing a white sequestrum in the centre that is surrounded by a well-defined black or dark brown circle. External findings associated with posterior scleritis include restriction of eye movements, sensitivity to palpation, and proptosis. Dilation of the fundus may be necessary to identify posterior scleritis. Funduscopy of the patient with posterior scleritis may also reveal papilloedema, choroidal folds, and retinal haemorrhage or detachment.
To differentiate mild scleritis from episcleritis, topical application of 2.5 per cent or 10 per cent phenylephrine may be used: it only blanches the superficial episcleral network without significant effect on the deep episcleral/scleral network. Ocular complications occur in 80 to 90 per cent of patients with necrotising or posterior scleritis, compared with approximately 50 per cent of patients with diffuse or nodular scleritis. Ocular complications of scleritis are as a result of the extending scleral inflammation and include peripheral ulcerative keratitis, uveitis, glaucoma, cataract and fundus abnormalities. The goals of treatment are to reduce morbidity and to prevent complications. Scleritis is a condition requiring multi-disciplinary management, involving rheumatologists, general physicians and ophthalmologists. Treatment almost always requires systemic therapy with steroids and immunosuppressive drugs. Topical steroids are rarely effective as a single therapy in treating scleritis. Therefore any patient with suspected scleritis should be referred urgently.

KERATOCONJUCTIVITIS SICCA (DRY EYE)
Keratoconjunctivitis sicca (KCS) is caused by problems with the tear film, which constitutes three layers: (1) a lipid layer produced by the meibomian glands; (2) an aqueous layer produced by the main and accessory lacrimal glands and (3) a hydrophilic mucin layer produced primarily by the conjunctival goblet cells. Abnormality of any of these layers produces an unstable tear film and symptoms of KCS. The commonest cause of KCS is inadequate tear volume (aqueous tear-deficient KCS), followed by excessive loss of tears due to accelerated evaporation because of poor tear quality (evaporative KCS). Decreased tearing is associated with increased age. In addition, irregularities in the blink mechanism or conditions affecting the regularity of the ocular surface (eg, pterygia, keratoconus) may further interfere with proper wetting of the cornea. Many drugs can also temporarily decrease lacrimal gland secretions, such as antihistamines, phenothiazine anti-anxiety medications, oral contraceptives and atropine derivatives. Collagen vascular disorders such as rheumatoid arthritis and Sjgren's syndrome are also commonly associated with dry-eye syndrome.
Typically, patients present with complaints of dry, burning eyes and a 'sandy' or 'gritty' foreign-body sensation. Occasionally, patients will report excess tearing (epiphora). Often, the symptoms are exacerbated by poor air quality and low humidity, and are more prominent later in the day. Upon inspection, most patients demonstrate a relatively white and quiet eye. Key slit lamp findings include a negligible tear meniscus at the lower lid and a reduced tear break-up time (TBUT), generally less than 10 seconds. Fluorescein staining may reveal punctate epithelial keratopathy in the interpalpebral region. In severe cases, the cornea and/or conjunctiva may also stain with rose bengal, and filaments (tags of mucus, epithelial cells and tear debris) may also stain with fluorescein and rose Bengal. This filamentary keratitis is an extreme sequela of KCS. There is a wide range of KCS patients, from mild or barely symptomatic to moderate and severe cases.
Supplemental lubrication is the mainstay of treatment for mild and moderate KCS. Mild cases can be treated with tear replacement drops a few times a day, or as required, such as hypromellose, or polyvinyl alcohol. More severe cases require more frequent application of drops, such as every one to two hours, but always remember that as soon as drops are being used at this frequency, there is a risk of preservative toxicity, and always look out for signs- such as a punctate keratitis affecting the whole cornea rather than the inferior half usually associated with KCS. When more frequent application is required, the tear gels may be appropriate to recommend to patients. These gels (eg, carbomers such as Viscotears or carmellose sodium preparations such as Celluvisc) last longer and may only be required two to four times a day. However, remember that these are significantly more expensive, and the majority of patients with mild KCS will be treatable with drops. Ointments can be used during the day, but they generally are reserved for bedtime use because of the blurred vision they cause - but as they last many hours, they are often essential for nocturnal comfort in KCS patients. As a general rule, preservative-free preparations should be used where frequent or prolonged application of lubricants is required.
Treatment of very severe KCS (especially associated with connective tissue disorders such as Sjgren's syndrome) may require coordination with a rheumatologist. Insertion of temporary punctal occlusion with collagen (dissolvable) or silicone (permanent) plugs may provide relief, but may cause epiphora in some patients. Some patients may benefit from humidifying goggles. There is some evidence that patients with moderate or severe KCS show inflammatory damage in the lacrimal gland and may benefit from topical immunosuppressant drugs such as ciclosporine.
Exposure keratitis may occur after a facial nerve palsy - occasionally lid surgery, such as a temporary partial tarsorrhaphy, or a canthal sling, or upper lid weights, may be required. A trigeminal nerve palsy may give rise to keratitis sicca secondary to loss of corneal sensation.

ANTERIOR SEGMENT TRAUMA
Foreign body
Foreign bodies such as glass, metal or organic material may lodge on or in the conjunctiva, sub-tarsus or cornea. They are usually superficial, but may adhere to the corneal epithelium (for example, a hot fragment of metal during grinding), or may be lodged in the stroma if projected with considerable force. The foreign object may set off an inflammatory cascade, resulting in dilation of the surrounding vessels and subsequent oedema of the lids, conjunctiva, and cornea. White blood cells also may be liberated, resulting in an anterior chamber reaction and/or corneal infiltration. If not removed, a foreign body can cause infection and/or tissue necrosis. Patients may complain of pain (typically relieved significantly with topical anaesthesia), foreign body sensation, photophobia and tearing. Visual acuity is normal or slightly depressed, the conjunctiva may be hyperaemic or ciliary injection may be present if an anterior chamber reaction occurs. There may be a visible foreign body, a rust ring (if metallic) and an epithelial defect that stains with fluorescein. Treatment is by removal of the foreign body after topical anaesthetic. Practitioners can attempt removal with a cotton bud, or even a needle if they have been taught to do so, followed by topical antibiotics and sometimes lubricants.
Remember always to evert the upper lid in a patient complaining of a foreign-body sensation. If an anterior uveitis develops topical steroids may be needed.

Corneal abrasion
Corneal abrasions are a common cause of Accident and Emergency department visits and can be managed in optometric practice. Patients usually present with a history of trauma, often related to gardening or a child's fingernail, and have eye pain (occasionally severe), tearing, photophobia, blepharospasm and a foreign body sensation often reported as being in the upper lid. This is because pain fibres are stimulated when the upper lid comes down over the area of corneal damage when blinking. Visual acuity is usually normal or slightly reduced. The reduction in acuity may result from excessive tearing, or if the abrasion lies within the central visual axis or is large. A topical anaesthetic such as proxymetacaine or benoxinate may facilitate the examination. Examination reveals bulbar conjunctival hyperaemia, and an area of epithelial loss of the cornea, staining with fluorescein (Figure 5). Superficial abrasions often heal completely and quickly (48-72 hours) without scarring. Deeper abrasions which extend below Bowman's membrane possess an increased risk for leaving a permanent opacity. Always remember to evert the upper lid to look for subtarsal foreign bodies (Figure 6).
Management includes broad-spectrum topical antibiotics until complete epithelial healing has occurred: ointment such as 1.0 per cent chloramphenicol is useful as it also lubricates the eye. As abrasions are very painful, topical cycloplegics may also reduce the ciliary spasm - cyclopentolate 1 per cent drops for the duration of pain, or a longer acting drop such as homatropine 2 per cent as a single dose is helpful. Patients may also benefit from topical non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac sodium (Voltarol), or if the practitioner does not have these, oral NSAIDs can be recommended for over the counter purchase. Daily review is recommended until the epithelial defect has closed (or has almost completely resolved), to exclude infectious keratitis. Remember in contact lens-associated abrasions to exclude microbial keratitis, and in particular to consider the possible diagnosis of Acanthamoeba keratitis. Practitioner should not attempt to manage bacterial keratitis in practice, as corneal scraping to determine which bacteria are involved and specialised antibiotic regimes may be required.
Hyphaema
A hyphaema is the accumulation of blood in the anterior chamber (AC), normally after trauma, although it may occur spontaneously with neovascularisation (eg diabetes mellitus) or vascular anomalies (eg, juvenile xanthogranuloma). Blood in the AC is not by itself necessarily harmful, but it may obstruct the outflow of aqueous humor, resulting in glaucoma. As it signifies significant trauma, and other ocular structures may be damaged, patients with a hyphaema after trauma require urgent referral to the hospital eye service.

Recurrent corneal erosion
Recurrent corneal erosion (RCE) is characterised by repeated, spontaneous disruption of the corneal epithelium. In most cases, RCE follows mechanical trauma, such as a corneal abrasion caused by a fingernail, and patients usually present with a history (lasting months or even years following the injury) with recurrent episodes of ocular pain that may also include foreign body sensation, photophobia, blepharospasm, decreased vision or lacrimation. The key to diagnosis is the history: these episodes, which may last for seconds or minutes, or more rarely hours, occur on waking during the night or in the morning, or they may follow eye rubbing.
Patients may describe difficulty opening their eye, because they sense that sudden opening may result in pain, and symptoms are usually on the side of the injury. There may be very little to see on examination once the symptoms have gone, with a clear cornea, but sometimes irregularity of the corneal epithelium, or epithelial microcysts, or some fluorescein staining may be seen (Figure 7). However, the diagnosis is made on the history, rarely on the signs. RCE occur because the epithelial cells have not fully attached to the underlying basement membrane and anterior stroma, and the drying of the eye at night causes disruption of the epithelial layer, with consequent symptoms similar to an abrasion. When symptoms are bilateral, they may signify a corneal epithelial dystrophy, with abnormal epithelial basement membrane adherence.
Patients with RCE can often be managed to resolution by the optometrist, as the mainstay of treatment is education of the patients and topical lubricants at night to try to prevent drying <2212> a greasy ointment such as Simple Eye Ointment or Lacrilube is best. Patients need to continue treatment for at least three months after the last symptoms to ensure that the epithelium is fully attached to the deeper layers of the cornea <2212> and warned that it may be many months or even years before full resolution. Some patients respond to lubricants plus taping the lids at night to try to prevent sudden opening of the eyes on waking. It has been shown that a significant number of patients with RCE have an abnormal tear film due to blepharitis/meibomian gland dysfunction, and so patients with recurrent symptoms despite lubrication and/or taping should be referred for a long course of oral tetracycline (eg doxycycline 100mg od for three months, or oxytetracycline 250mg bd) which has been shown to facilitate healing. A few patients have symptoms despite this, and may benefit from bandage contact lenses, excimer laser corneal keratectomy, or corneal debridement.

FURTHER READING
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Mfazo Hove is senior house officer and Christopher Hammond is consultant ophthalmologist at West Kent Eye Centre, Princess Royal University Hospital, Bromley