Ординатура / Офтальмология / Английские материалы / Clinical Ophthalmology A Systematic Approach 7th Edition_Kanski, Bowling_2011

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Allergic conjunctivitis

Atopy is a genetically determined predisposition to hypersensitivity reactions upon exposure to specific environmental antigens. Clinical manifestations include the various forms of allergic conjunctivitis, as well as hay fever (seasonal allergic rhinitis), asthma and eczema. Allergic conjunctivitis is a Type I (immediate) hypersensitivity reaction, mediated by degranulation of mast cells in response to the action of IgE; there is evidence of an element of Type IV hypersensitivity in at least some forms.

Acute allergic conjunctivitis

Acute allergic conjunctivitis is a common condition caused by an acute conjunctival reaction to an environmental allergen, usually pollen. It is typically seen in younger children after playing outside in spring or summer.

1Presentation is with acute itching and watering, associated with severe chemosis (Fig. 5.11).

2Treatment is not usually required and the conjunctival swelling settles within hours as the acute increase in vascular permeability resolves. Cool compresses can be used and a single drop of adrenaline 0.1% may reduce extreme chemosis.

Fig. 5.11 Severe chemosis in acute allergic conjunctivitis

Seasonal and perennial allergic conjunctivitis

Seasonal and perennial allergic conjunctivitis are subacute conditions that differ from each other by the timing of exacerbations because of different stimulating allergens in each.

1Seasonal allergic conjunctivitis (‘hay fever eyes’), worse during the spring and summer, is the more common. The most frequent allergens are tree and grass pollens, although the specific allergen varies with geographic location.

2Perennial allergic conjunctivitis causes symptoms throughout the year, generally worse in the autumn when exposure to house dust mites, animal dander and fungal allergens is greatest. It is less common and tends to be milder than the seasonal form.

Diagnosis

1Presentation is with transient acute or subacute attacks of redness, watering and itching, associated with sneezing and nasal discharge.

2Signs, which typically resolve completely between episodes, consist of conjunctival hyperaemia and a relatively mild papillary reaction, variable chemosis and lid oedema.

3Investigations are generally not performed although conjunctival scraping in more active cases may demonstrate the presence of eosinophils.

Treatment

1Artificial tears for mild symptoms.

2Mast cell stabilizers (sodium cromoglicate, nedocromil sodium, lodoxamide) need to be used for a few days before exerting maximal effect, but are suitable (except lodoxamide) for long-term use if required.

3Antihistamines (emedastine, epinastine, levocabastine, bepotastine) can be used for symptomatic exacerbations and are as effective as mast cell stabilizers.

4Combined preparation of an antihistamine and a vasoconstrictor (antazoline with xylometazoline – Otrivin-Antistin®).

5 Dual action antihistamine and mast cell stabilizers (azelastine, ketotifen, olopatadine) are often very effective for exacerbations. 6 Topical steroids are effective but rarely necessary.

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7Oral antihistamines may be indicated for severe symptoms. Some, such as diphenhydramine, cause significant drowsiness and may be useful in aiding sleep; others such as loratadine have less sedative action.

Vernal keratoconjunctivitis

Pathogenesis

Vernal keratoconjunctivitis (VKC) is a recurrent bilateral disorder in which both IgEand cell-mediated immune mechanisms play important roles. It primarily affects boys and onset is generally from about the age of 5 years onwards (mean age 7 years). Ninety-five per cent of cases remit by the late teens although many of the remainder develop atopic keratoconjunctivitis. VKC is rare in temperate regions but relatively common in warm dry climates such as the Mediterranean, sub-Saharan Africa, and the Middle East. In temperate regions over 90% of patients have other atopic conditions such as asthma and eczema and two-thirds of cases have a family history of atopy. VKC often occurs on a seasonal basis, with a peak incidence over late spring and summer, although there may be mild perennial symptoms.

Classification

1Palpebral VKC primary involves the upper tarsal conjunctiva. It may be associated with significant corneal disease as a result of the close apposition between the inflamed conjunctiva and the corneal epithelium.

2Limbal disease typically affects black and Asian patients.

3Mixed VKC has features of both palpebral and limbal disease.

Diagnosis

The diagnosis is clinical and investigations are generally not indicated.

1Symptoms consist of intense itching, which may be associated with lacrimation, photophobia, a foreign body sensation, burning and thick mucoid discharge. Increased blinking is common.

2Palpebral disease

•Early-mild disease is characterized by conjunctival hyperaemia and diffuse papillary hypertrophy on the superior tarsus (Fig. 5.12A).

•Macropapillae (<1 mm) have a flat-topped polygonal appearance reminiscent of cobblestones (Fig. 5.12B).

•Progression to giant papillae (>1 mm) can occur, as adjacent smaller lesions amalgamate when dividing septa rupture.

•Mucus deposition between giant papillae (Fig. 5.12C).

•Decreased disease activity is characterized by milder conjunctival injection and decreased mucus production (Fig. 5.12D).

3Limbal disease

•Gelatinous limbal conjunctiva papillae that may be associated with transient apically-located white cellular collections (Horner-Trantas dots – Fig. 5.13A-C).

•In tropical regions limbal disease may be very severe (Fig. 5.13D).

4Keratopathy is more frequent in palpebral disease and may take the following forms:

aSuperior punctate epithelial erosions associated with sheets of mucus on the superior cornea (Fig. 5.14A).

bEpithelial macroerosions (Fig. 5.14B) caused by a combination of epithelial toxicity from inflammatory mediators and a direct mechanical effect from papillae.

cPlaques (Fig. 5.14C) and ‘shield’ ulcers (Fig. 5.14D) may develop in palpebral or mixed disease when the exposed Bowman membrane becomes coated with mucus and calcium phosphate, leading to inadequate wetting and delayed reepithelialization. This development is serious and warrants urgent attention to prevent secondary bacterial infection.

dSubepithelial scars that are typically grey and oval, and may affect vision (Fig. 5.14E).

ePseudogerontoxon can develop in recurrent limbal disease. It is characterized by a paralimbal band of superficial scarring resembling arcus senilis, adjacent to a previously inflamed segment of the limbus (Fig. 5.14F).

fOther manifestations

•Vascularization does not tend to be prominent, though some peripheral superficial vessel ingrowth is common, especially superiorly.

•Keratoconus and other forms of corneal ectasia are more common in VKC.

•Herpes simplex keratitis is more common than average, though less so than in atopic keratoconjunctivitis (AKC). It can be aggressive and is occasionally bilateral.

5 Eyelid disease is usually mild, in contrast to AKC.

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Fig. 5.12 Palpebral vernal disease. (A) Diffuse papillary hypertrophy; (B) macropapillae; (C) giant papillae and mucus; (D) relatively inactive disease

(Courtesy of S Tuft – figs B and D)

Fig. 5.13 Limbal vernal disease. (A) Sparse limbal papillae; (B) papillae with Horner–Trantas dots; (C) extensive papillae; (D) extremely severe involvement

(Courtesy of S Tuft – fig. B)

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Fig. 5.14 Keratopathy in vernal disease. (A) Superior punctate erosions and sheets of mucus; (B) macroerosion; (C) early plaque formation; (D) plaque and ‘shield’ ulcer; (E) oval subepithelial scarring; (F) pseudogerontoxon and limbal papillae

(Courtesy of S Tuft – figs A, B, C and F)

Atopic keratoconjunctivitis

Pathogenesis

AKC is a rare bilateral disease that typically develops in adulthood (peak incidence 30–50 years) following a long history of eczema. Asthma is also extremely common in these patients. About 5% have suffered from childhood VKC. There is little or no gender preponderance. AKC tends to be chronic and unremitting with a relatively low expectation of eventual resolution, and is associated with significant visual morbidity. Whereas VKC is more frequently seasonal, AKC tends to be perennial, although it is often worse in the winter. Patients are sensitive to a wide range of airborne environmental allergens.

Diagnosis

The distinction between AKC and VKC is clinical.

1Symptoms are similar to those in VKC, but are frequently more severe and unremitting.

2Eyelids

•Skin changes (Fig. 5.15A) consist of erythema, dryness, scaliness and thickening, sometimes with fissuring, and scratches (‘excoriation’) due to intense itching.

•Associated chronic staphylococcal blepharitis and madarosis are common.

•Keratinization of the lid margin.

•Hertoghe sign is characterized by absence of the lateral portion of the eyebrows.

•Tightening of the facial skin may cause lower lid ectropion and epiphora.

3Conjunctival involvement is preferentially inferior palpebral, whereas in VKC it is worse superiorly.

•Discharge is generally more watery than the stringy mucoid discharge in VKC.

•Papillae are initially smaller than in VKC although larger lesions may develop later.

•Diffuse conjunctival infiltration and scarring may give a whitish, featureless appearance (Fig. 5.15B).

•Cicatricial changes can lead to moderate symblepharon formation, forniceal shortening (Fig. 5.15C) and keratinization of the caruncle (Fig. 5.15D).

•Limbal involvement similar to that of limbal VKC can be seen, including Horner–Trantas dots.

4Keratopathy

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aPunctate epithelial erosions over the inferior third of the cornea are common (Fig. 5.15E).

bPersistent epithelial defects (Fig. 5.15F), sometimes with associated focal thinning, can occasionally progress to perforation.

cPlaque formation may occur.

dPeripheral vascularization (see Fig. 5.15F) and stromal scarring are more common than in VKC.

eOther manifestations

•Predisposition to secondary bacterial and fungal infection, and to aggressive herpes simplex keratitis.

•Keratoconus is common (about 15%) and as with VKC it is thought to be secondary to chronic ocular rubbing.

5Cataract

•Presenile shield-like anterior or posterior subcapsular cataracts are common and may be exacerbated by long-term steroid therapy.

•Because of the high lid margin carriage of S. aureus, cataract surgery carries an increased risk of endophthalmitis.

6Retinal detachment is more common than in the general population.

Fig. 5.15 Atopic disease. (A) Severe eyelid involvement; (B) infiltration and scarring of the tarsal conjunctiva; (C) forniceal shortening; (D) keratinization of the caruncle; (E) punctate epithelial erosions; (F) persistent epithelial defect and peripheral corneal vascularization

(Courtesy of S Tuft)

Treatment of VKC and AKC

The management of VKC does not differ substantially from that of AKC, although the latter is generally less responsive and requires more intensive and prolonged treatment.

General measures

1Allergen avoidance, if possible. An allergy specialist opinion can be requested if appropriate; allergen patch testing is sometimes useful, but often gives non-specific findings.

2Cool compresses may be helpful.

3Lid hygiene should be used for associated staphylococcal blepharitis. Moisturizing cream such as E45 can be applied to dry fissured skin.

Local treatment

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1Mast cell stabilizers may reduce the frequency of acute exacerbations and the need for steroids and so form the basis of most regimens, although they are seldom effective in isolation. Several days of treatment are needed for a reasonable response and in some cases long-term therapy may be needed (lodoxamide is not licensed for long-term use). In some patients adding a NSAID (ketorolac, diclofenac) may give added benefit.

2Antihistamines are suitable for acute exacerbations but generally not for long-term use. A trial of several different agents may be worthwhile.

3Combined preparations of an antihistamine and a vasoconstrictor usually offer only limited relief whereas dual action antihistamine/mast cell stabilizers are often effective.

4Steroids are used for (a) severe exacerbations of conjunctivitis and (b) significant keratopathy in which reducing conjunctival activity leads to corneal improvement.

•Steroids (fluorometholone 0.1%, rimexolone 1%, prednisolone 0.5% or loteprednol etabonate 0.2% or 0.5%) are usually prescribed in short but intensive courses, aiming for prompt tapering. Although the risk of elevation of intraocular pressure is low, monitoring is advisable if long-term medication is necessary, particularly in AKC.

•Stronger preparations such as prednisolone 1% can be used but carry a higher risk of steroid-induced glaucoma.

•Supratarsal steroid injection may be considered in severe palpebral disease, for non-compliance or for patients resistant to conventional therapy. The injection is given into the conjunctival surface of the anaesthetized everted upper eyelid; 0.1 mL of betamethasone sodium phosphate 4 mg/mL (Betnesol), dexamethasone 4 mg/mL or triamcinolone 40 mg/mL is given.

5Immune modulators

aCiclosporin 0.05% b.d. may be indicated if steroids are ineffective, inadequate or poorly tolerated, or as a steroid-sparing agent in patients with severe disease. The drug may cause ocular irritation and blurred vision when used for several weeks and relapses may occur if it is stopped suddenly. Its efficacy as a first line agent for long-term therapy requires further study.

bTacrolimus 0.03% ointment can be effective in AKC for severe eyelid disease. Instillation into the fornices has been effective in modulating conjunctival inflammation in refractory cases.

6Other measures

aAntibiotics are used in conjunction with steroids in severe keratopathy to prevent or treat bacterial infection.

bAcetylcysteine is a mucolytic agent that is useful in VKC for dissolving mucus filaments and deposits, and addressing early plaque formation.

Systemic treatment

1Antihistamines help itching, promote sleep and reduce nocturnal eye rubbing. Because other inflammatory mediators are involved besides histamines, effectiveness is not assured.

2Antibiotics (doxycycline 50–100 mg daily for 6 weeks or azithromycin 500 mg once daily for 3 days) to reduce blepharitisaggravated inflammation, usually in AKC.

3Immunosuppressive agents (e.g. steroids, ciclosporin, tacrolimus, azathioprine) may be effective at relatively low doses in AKC unresponsive to other measures. Short courses of high-dose steroids may be necessary to achieve rapid control in severe disease. Monoclonal antibodies against T cells have shown some promise in refractory cases.

4Aspirin may be useful in VKC, although the risk of Reye's syndrome means it should be avoided in children and adolescents (the group predominantly affected by VKC).

Surgery

1Bandage contact lens wear may be appropriate to aid the healing of persistent epithelial defects.

2Superficial keratectomy may be required to remove plaques or debride shield ulcers and allow epithelialization. Medical treatment must be maintained until the cornea has re-epithelialized in order to prevent recurrences. Excimer laser phototherapeutic keratectomy is an alternative.

3Surface maintenance-restoration surgery such as amniotic membrane overlay grafting or lamellar keratoplasty, or eyelid procedures such as botulinum toxin-induced ptosis or lateral tarsorrhaphy, may be required for severe persistent epithelial defects or ulceration. Gluing may be appropriate for focal (‘punched-out’) corneal perforations.

Giant (mechanically-induced) papillary conjunctivitis

Pathogenesis

Mechanically-induced papillary conjunctivitis, the severe form of which is known as giant papillary conjunctivitis (GPC), can occur secondary to a variety of mechanical stimuli of the tarsal conjunctiva. It is most frequently seen with contact lens (CL) wear, when it is termed contact lens-associated papillary conjunctivitis (CLPC). The risk is increased by the build-up of proteinaceous deposits and cellular debris on the contact lens surface (Fig. 5.16). Ocular prostheses (Fig. 5.17), exposed sutures and scleral buckles, corneal surface irregularity and filtering blebs can all be responsible. A related phenomenon is the so-called ‘mucus fishing syndrome’, when, in a variety of underlying anterior segment disorders, patients develop or exacerbate a chronic papillary reaction due to repetitive manual removal of mucus.

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Fig. 5.16 Contact lens deposits

Fig. 5.17 Ocular prosthesis causing giant papillary conjunctivitis

Diagnosis

1Symptoms consist of a foreign body sensation, redness, itching, increased mucus production, blurring and loss of CL tolerance. Symptoms may be worse after lens removal. Patients should be questioned about CL cleaning and maintenance.

2Signs

•Variable mucous discharge.

•Protein deposits on the CL.

•Excessive CL mobility due to upper lid capture.

•Superior tarsal hyperaemia and initially fine-medium size papillae (>0.3 mm).

•Focal apical ulceration and whitish scarring may develop on larger papillae in advanced cases.

•Keratopathy is rare because of the relatively subdued secretion of inflammatory cytokines.

•Ptosis may occur mainly as a result of irritative spasm and tissue laxity secondary to chronic inflammation.

Treatment

Other causes of conjunctival papillae should be excluded, as well as CL intolerance due to other causes such as solutions and dry eyes.

1Remove the stimulus

•CL wear should be discontinued for several weeks and the current lenses replaced.

•For mild–moderate disease, this may be adequate for resolution, sometimes in conjunction with reduced wearing time.

•In severe disease a longer interval without lens wear may be needed.

•Removal of other underlying causes such as exposed sutures or scleral buckle.

•Assessment of the status and fit of ocular prosthesis.

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•Refashioning of filtering blebs or glaucoma drainage devices.

2Ensure effective cleaning of CL or prosthesis

•Changing the type of CL solution, particularly preservative-containing preparations.

•Switching to monthly then daily disposable CL if the condition persists after renewing non-disposable lenses.

•Rigid lenses carry a lesser risk of CLPC (5%) because they are easier to clean effectively.

•Cessation of CL wear and substituting spectacles or refractive surgery for severe or refractory disease.

•Regular (at least weekly) use of contact lens protein removal tablets.

•Prostheses should be cleaned and polished.

3Topical

•Mast cell stabilizers should be non-preserved in patients wearing soft contact lenses, or can be instilled when the lenses are not in the eye, with a delay of perhaps half an hour after drop instillation prior to lens insertion. Most can be continued long-term if necessary.

•Antihistamines, non-steroidal anti-inflammatory agents and combined antihistamines/mast cell stabilizers may each be of benefit.

•Topical steroids can be used for the acute phase of resistant cases, particularly those where effective removal of the stimulus is difficult, as in bleb-related disease.

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Conjunctivitis in blistering mucocutaneous disease

Mucous membrane pemphigoid

Definition

Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), comprises a group of chronic autoimmune mucocutaneous blistering diseases characterized by linear antibody and complement deposition at epithelial basement membranes. A wide range of epithelial tissues can be involved including the skin and mucous membranes of the mouth, nasopharynx, upper airways, genitalia, and upper and lower gastrointestinal tract, as well as the conjunctiva. Particular clinical forms of MMP tend preferentially to involve specific target tissues or body regions such as bullous pemphigoid (BP) that shows a predilection for skin, although frequently also affects the mouth and other tissues. Ocular cicatricial pemphigoid (OCP) involves the conjunctiva in the majority of cases and causes progressive scarring (cicatrization). The disease typically presents in old age and affects females more commonly than males by a 2 : 1 ratio. Other causes of cicatrizing conjunctivitis are set out in Table 5.2.

Table 5.2 -- Causes of conjunctival cicatrization

•Mucous membrane pemphigoid

•Stevens–Johnson syndrome-toxic epidermal necrolysis (Lyell syndrome)

•Atopic (and less commonly vernal) keratoconjunctivitis

•Conjunctival chemical and thermal burns

•Severe bacterial or viral conjunctivitis

•Trachoma

•Drug-induced (‘pseudopemphigoid’)

•Other: epidermolysis bullosa, pemphigus vulgaris, linear IgA disease, dermatitis herpetiformis, lichen planus, porphyria cutanea tarda, xeroderma pigmentosum, scleroderma, xerophthalmia (vitamin A deficiency)

Pathogenesis

An unknown trigger (possibly contact with a particular micro-organism) in genetically predisposed individuals leads to a Type II hypersensitivity response with antibodies binding at the basement membrane zone (BMZ), the activation of complement and recruitment of inflammatory cells. A characteristic of the acute phase of the inflammatory process is localized separation of the epidermis from the dermis at the BMZ. The release of cytokines causes fibroblast activation with consequent progression to scarring. Different clinical forms of MMP tend to be associated with differing target antigens. In bullous pemphigoid, it is one or more hemidesmosomal glycoproteins, and in many cases of OCP, a component of an integrin (a protein mediating cell–cell and cell–matrix interaction) is responsible.

Ocular features

1Presentation is with the insidious onset of non-specific conjunctivitis which is bilateral, but frequently asymmetrical. Because of its rarity, the diagnosis is often overlooked or there may be misdiagnosis, with specific treatment being delayed.

2Conjunctiva

•Papillary conjunctivitis, diffuse hyperaemia and oedema, and necrosis in severe cases (Fig. 5.18A).

•Fine lines of subconjunctival fibrosis and shortening of the inferior fornices (Fig. 5.18B).

•Flattening of the plica and keratinization of the caruncle (Fig. 5.18C).

•Symblepharon (plural symblephara) is an adhesion between the bulbar and palpebral conjunctiva (Fig. 5.18D).

•Dry eye is caused by a combination of destruction of goblet cells and accessory lacrimal glands as well as occlusion of the main lacrimal ductules.

•The chronically progressive course of the disease may be punctuated by exacerbations.

•Disease progression should be regularly monitored by measuring the depth of the fornices and noting the position of adhesions.

3Cornea

•Epithelial defects associated with drying and exposure (Fig. 5.19A).

•Infiltration and peripheral vascularization (Fig. 5.19B).

•Keratinization and ‘conjunctivalization’ of the corneal surface following damage to the limbus and consequent epithelial stem cell failure (Fig. 5.19C).

•End-stage disease is characterized by total symblepharon and corneal opacification (Fig. 5.19D).

4Eyelids

•Aberrant (dysplastic) lashes, chronic blepharitis and keratinization of the lid margin.

•Ankyloblepharon, in which there are adhesions at the outer canthus between the upper and lower lids.

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(Courtesy of S Tuft)

Fig. 5.19 Keratopathy in ocular cicatricial pemphigoid. (A) Epithelial defect; (B) peripheral vascularization and infiltration; (C) keratinization and ankyloblepharon; (D) end-stage disease

(Courtesy of S Tuft)

Systemic features

1Mucosal involvement is very common and is characterized by subepidermal blisters, most frequently oral (Fig. 5.20A). The blisters rupture within a day or two leaving erosions and ulcers that heal without significant scarring. Ulcers in other sites typically heal with scarring which may result in stricture formation. Stricture of the oesophagus can result in regurgitation and aspiration of food.

Laryngeal or tracheal stenosis may be life-threatening.

2Skin lesions are less common (25%) and present as tense blisters and erosions. They may involve the head and neck (Fig. 5.20B),

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