ALLERGIC EYE DISEASE

Allergic eye disease in its various forms is a common cause of ocular morbidity in both primary care and specialist practice. The external eye is under constant immunological challenge from a wide variety of substances; this may lead to the development of one of many conditions that can be loosely grouped as ‘allergic eye disease’. The chief factors determining the outcome of such challenges are the severity and duration of the antigenic load and the immunological status of the individual. Local or systemic immune mechanisms may be involved to produce immediate hypersensitivity, complement-mediated or delayed hypersensitivity reactions. The spectrum of allergic conjunctivitis (Table 5.1) ranges from mild self-limiting seasonal conjunctivitis to atopic keratoconjunctivis in which vision is threatened by corneal vascularization, herpetic epithelial infection and the long-term complications of topical corticosteroid therapy. Although patients complain of red, sore and discharging eyes, itchiness is the characteristic symptom of allergic eye disease. Patients also have an increased risk of keratoconus and atopic cataract. Increased levels of IgE and eosinophils are found in the conjunctiva and a wide range of inflammatory mediators have been shown to be involved in the pathogenesis.

Treatment involves identification and avoidance of the offending antigen and the administration of antihistamines, mast cell stabilizers or steroids. Mild disease responds to topical antihistamine or mast cell-stabilizing agents alone but corneal involvement requires topical steroids, often over prolonged periods with surveillance for steroid side-effects.

IMMEDIATE HYPERSENSITIVITY REACTIONS

Fig. 5.1 Acute periorbital oedema is a common manifestation of immediate hypersensitivity and appears within minutes of exposure. It may follow the systemic administration of antigen in a sensitized individual such as the ingestion of foods or drugs. The reaction is frequently associated with high titres of circulating IgE antibody, being mediated by the release of histamine and other pharmacologically active substances from mast cells in the skin and mucosal tissues. It usually produces symmetrical bilateral lid oedema which may also be accompanied by conjunctival chemosis and urticarial skin rashes. The onset is rapid but the signs usually improve within a few hours. Acute unilateral signs may result from local inoculation and histamine release in the skin, as in this patient where the reaction followed an insect bite.

Fig. 5.2 Acute conjunctival chemosis may occur in the absence of lid swelling as an immediate hypersensitivity response to local inoculation of antigenic substances (frequently pollens) directly on to the conjunctiva of a sensitized individual. The level of response depends on the degree of previous sensitization and the dose of antigen. In this patient, although both conjunctiva are chemotic and slightly hyperaemic, the signs are more pronounced in the left eye.

Fig. 5.3 Phlyctens are inflammatory nodules usually seen on the nasal limbus with an associated hyperaemia. They are bilateral and are usually seen in children and young adults. Phlyctens represent a lymphocyte cell-mediated response in a previously sensitized individual. They are associated with a variety of antigens; staphlococci are now the commonest cause, but in the past the main cause was tuberculosis.

ALLERGIC CONJUNCTIVITIS

Fig. 5.4 Atopic blepharoconjunctivitis is typified by thickening of eyelid and periocular skin. Conjunctival inflammation is moderate and keratopathy is absent.

Fig. 5.5 Atopic keratoconjunctivitis is uncommon and is usually seen in young men with atopic dermatitis and a history of childhood eczema. The ocular changes are seen in early adult life; they are bilateral, symmetrical and persistent for many years. The conjunctival changes carry a significant risk of sight-threatening complications which include corneal vascularization, herpes simplex viral keratitis and steroid-induced glaucoma. Cicatrizing conjunctivitis and fornix shortening results from progressive subepithelial scarring.

VERNAL KERATOCONJUNCTIVITIS

Vernal keratoconjunctivitis (VKC) is an ocular manifestation of atopy. There is frequently a history of eczema, hayfever and asthma which characteristically starts early in life. The disease is bilateral and chronic with seasonal exacerbations and remissions and predominates in young males. It is common in the hot dry climate of the Middle East. Patients are usually allergic to multiple antigens and have seasonal exacerbations, often improving around puberty. Itching and ocular discomfort with mucoid discharge are the predominant symptoms.

The aim of treatment during acute exacerbations is to control symptoms by reducing conjunctival inflammation. In less severe forms of the disease single agents may be successful in controlling the disease but in severe cases intensive topical steroids are usually needed. Mucolytic preparations such as acetylcysteine drops can be useful in removing excess mucus. It is important to reduce topical steroids as soon as possible to avoid ocular complications such as glaucoma and this may be facilitated by the additional use of a mast cell-stabilizing drop for its steroid-sparing effect.

Fig. 5.6 This boy, who suffers from VKC, shows a typical eczematous rash on his forehead and cheeks. There is an associated slight bilateral ptosis reflecting the chronic inflammation on the upper tarsal conjunctiva.

Fig. 5.7 Giant papillae on the upper tarsus, typically described as having a ‘cobblestone’ appearance, are the hallmark of VKC. Although these papillae persist during quiescent phases they become swollen and infiltrated by oedema and inflammatory cells with abundant abnormal mucus both on the surface and in the crevices between the papillae when the disease becomes active, as in this example.

Fig. 5.8 This eye shows less conjunctival swelling and mucus discharge, indicating inactive VKC.

Fig. 5.9 A histological section of VKC shows typical papillae with epithelial downgrowth to form tubules and cysts. The papillae have a loose stroma in which inflammatory cells are seen. Eosinophils and basophils are present in large numbers during the active phase of the disease.

Fig. 5.10 Limbal follicles may occur in VKC and are seen more commonly in black patients in the absence of marked tarsal papillae. This is sometimes known as the ‘limbal’ form of the disease. These limbal lesions are heavily infiltrated with inflammatory cells and appear as greyish, gelatinous swellings, especially around the superior limbus. The blood vessels are not unduly prominent and no mucus is visible.

Fig. 5.11 Trantas’ dots are a feature of VKC. They are small, white, elevated, epithelial lesions seen on the limbal lesions at the superior limbus and contain eosinophils. In this example they are associated with a greyish corneal infiltrate.

By courtesy of Professor R J Buckley.

Fig. 5.12 This patient illustrates the early corneal changes seen in vernal disease. There is a fine punctate epithelial keratopathy consisting of fine grey dots which has become confluent in some areas. Eosinophilic major basic protein from disrupted eosinophils is cytotoxic and thought to play a major role in vernal keratopathy.

By courtesy of Professor R J Buckley.

Fig. 5.13 A vernal ulcer characteristically develops in the upper half of the cornea during active phases of tarsal disease and is shown here stained with fluorescein. The edge of the ulcer is surrounded by whitish, heaped-up epithelium. The base is composed of abnormal mucus that is deposited with fibrin and other serum constituents as a grey plaque. When established, this plaque prevents healing from occurring. An area of superficial corneal infiltration can be seen nearer the limbus on the nasal side of the cornea.

By courtesy of Professor R J Buckley.

Fig. 5.14 This is a more severe example of a vernal ulcer showing a large area of central ulceration with established plaque formation. This image illustrates the nonwetting properties of the plaque and the raised epithelial edge, which is indicative of poor healing in the presence of plaque. Peripheral to the ulcer, the cornea is relatively clear although corneal vascularization from the limbus has commenced. The conjunctiva is hyperaemic and a strand of typically ‘stringy’ mucus lies on the surface of the eye.

GIANT PAPILLARY CONJUNCTIVITIS

Fig. 5.15 Giant papillary conjunctivitis is a chronic condition affecting the upper tarsal conjunctiva; it is caused by mechanical irritation. The condition is seen, for example, in patients wearing contact lenses, ocular prostheses or in association with protruding nylon suture ends following corneal or cataract surgery. Patients complain of itching, ocular discomfort and a stringy discharge. The aetiology appears to be mast cell degranulation initiated by mechanical trauma. In this example, a hard contact lens has produced giant papillae at the medial end of the upper border of the tarsus with a fine papillary reaction elsewhere. The condition is clinically distinguishable from vernal conjunctivitis by the lack of changes elsewhere in the conjunctiva, absence of an atopic history, and the presence of an associated foreign body. The conjunctival changes resolve with removal of the irritating stimulus.

OCULOCUTANEOUS CICATRICIAL DISORDERS

This is a heterogenous group of conditions in which the skin, eye and mucous membranes are damaged through immune reactions giving rise to, amongst other effects, a cicatrizing conjunctivitis. Included in this group are cicatricial pemphigoid, erythema multiforme or Stevens–Johnson syndrome, linear IgA disease, dermatitis herpetiformis and some drug-induced disorders. The diagnosis, which involves the cooperation of ophthalmologist and dermatologist, may depend on tissue biopsy and immunohistochemistry. Bulbar conjunctival biopsies can be taken without risking disease exacerbation and biopsy of skin or other mucosal lesions may also be useful to support a diagnosis.

OCULAR CICATRICIAL PEMPHIGOID

This autoimmune disorder is caused by autoantibodies to mucosal basement membrane. About 70 per cent of patients presenting with cutaneous pemphigoid have ocular changes, whereas in those presenting with ocular disease about 20 per cent have cutaneous disease. The condition usually presents to the ophthalmologist in elderly women as bilateral chronic conjunctival inflammation; the presentation is acute in a minority, and in some follows conjunctival or lid surgery. The clinical diagnosis of pemphigoid is suggested by the presence of one or more of the other features of the disease, which include scalp lesions and oesophageal, buccal and genital ulceration. Not all features may be present, nor are they necessarily all active simultaneously, but it may be possible to find scarring as evidence of earlier activity.

The clinical course is of progressive conjunctival shrinkage with acute inflammatory exacerbations. Patients need to be assessed for the degree of conjunctival fibrosis and the amount of active inflammation. In the early stages there is symblepharon formation in the lower fornix, with loss of the caruncle. With active disease, areas of conjunctival ulceration stain with fluorescein and resolve with further scarring. Progressive conjunctival scarring leads to increasing symblepharon formation, entropion and tear film instability, which in turn causes corneal opacification. In mild, slowly progressive disease, therapy may not be justified. First-line treatment is with dapsone or sulfapyridine, but severe progressive disease may require more potent systemic immunosuppressive drugs.

Fig. 5.16 Ulceration of the conjunctiva in active mucous membrane pemphigoid is clearly delineated in this case following instillation of fluorescein.

Fig. 5.17 Extensive palatal ulceration is visible in this edentulous patient (left). The painful mouth ulcers had been erroneously attributed by the patient to poorly fitting dentures. Buccal mucous membrane pemphigoid (right) is also characterized by tongue involvement, as in this patient in whom blisters are seen alongside sloughing ulcers, which indicate the site of a previous blister.

By courtesy of Dr F M Tatnall.

Fig. 5.18 In early pemphigoid, conjunctival cicatrization usually obliterates the caruncle (top left), producing progressive loss of the fornices and symblepharon formation. This example (top right) shows symblepharon formation in early disease which has been arrested by therapy. Inexorable progression to late disease is associated with scarring that almost obliterates the inferior fornix (bottom left).

Fig. 5.19 This example illustrates a late stage of ocular cicatricial pemphigoid with gross symblepharon formation, corneal scarring and vascularization resulting from corneal drying. This is associated with loss of tears and mucus-producing cells in the conjunctiva. The lashes have been removed during the course of the disease to prevent further corneal trauma from trichiasis and cicatricial entropion.

Fig. 5.20 Histological examination of the conjunctiva in mucous membrane pemphigoid.

ERYTHEMA MULTIFORME

Erythema multiforme is an immunologically mediated vasculitis that produces focal lesions in the skin and, in its variant known as Stevens–Johnson syndrome, in the mucous membranes. The condition frequently follows the administration of drugs, such as sulfonamides or phenobarbitone, or bacterial and viral infections, such as herpes simplex. The disease is characterized by its acute onset and lasts 2–3 weeks, during which time complete resolution occurs. In some cases, serious complications (e.g. renal failure) may develop.

Fig. 5.21 The rash of erythema multiforme starts on the extensor surfaces of the arms and legs, and spreads to involve the trunk. The skin lesions consist of an area of erythema surrounding a paler centre, which may ulcerate to give a ‘target’ appearance. The lesions heal without scarring.

Fig. 5.22 In its more severe form, with mucous membrane involvement, erythema multiforme is known as Stevens–Johnson syndrome. This patient shows extensive oral ulceration involving the upper and lower lips. Patients are acutely ill, losing serum and protein through their skin; they are unable to eat and at grave risk of secondary infection. Systemic steroids, fluid replacement and prophylactic antibiotics are the basis of treatment.

Fig. 5.23 Stevens–Johnson syndrome produces focal ulcerative changes in the conjunctiva where a severe pseudomembranous conjunctivitis may also occur in the acute stages. In the resolving phase healing is accompanied by scar formation which is typically focal, as seen here on the lower tarsus. The ocular surface is affected as a secondary phenomenon due to tear film changes.

Fig. 5.24 Symblepharon formation is a frequent result of conjunctival involvement in erythema multiforme. In this example a fibrous band is seen at the medial canthus, stretching from the lower punctum across to the bulbar conjunctiva. These symblephara are narrow, in contrast to the broad bands of ocular pemphigoid.

Fig. 5.25 Histological changes in end-stage erythema multiforme may be similar to those seen in mucous membrane pemphigoid. Patchy epidermidalization of the conjunctiva has taken place as evidenced by rete ridge formation, thickened epithelium with a prickle cell layer, and keratin formation giving the histological appearance of skin without hair follicles or other appendages. The underlying stroma shows marked fibrosis. In the acute phase of the disorder a mononuclear cell infiltrate in the stroma would be characteristic.

GRAFT VERSUS HOST DISEASE

Chronic graft versus host (GVH) disease occurs following bone marrow transplantation for conditions such as acute myeloid leukaemia and may cause inflammatory lesions of various mucous membranes including the mouth, oesophagus and conjunctiva that progress to cicatrization. Patients usually present with dry eye symptoms.

Fig. 5.26 This patient developed GVH disease that was treated successfully by immunosuppressive therapy 12 months after bone marrow transplantation. The scarring on the upper tarsus shown in this picture has persisted unchanged for 10 years, punctal occlusion and intensive artificial tear supplements were required to maintain the corneal surface.

EPIDERMOLYSIS BULLOSA

This is a group of rare, recessively inherited disorders in which basement membrane defects in the skin and mucous membranes are associated with severe scarring in relationship to minor trauma.

Fig. 5.27 Scarring of the hands is severe in children with epidermolysis bullosa. They also develop oral, oesophageal and anal strictures. Great care is required during both examination and anaesthesia to prevent further skin damage from minor trauma.

Fig. 5.28 Children develop symblepharon, particularly at the medial and lateral canthi. Recurrent corneal erosions are common and are associated with a fine subepithelial scarring.

OCULAR SURFACE DISORDERS

A healthy ocular surface is an essential requirement for precise corneal refraction and transparency and for the protection of the globe from disease. It is maintained by the total environment provided by the eyelids, conjunctiva and adnexal secretory glands; the malfunction of any element can lead to secondary ocular surface disease. The tear film consists of an inner film of mucus secreted by the goblet cells, a middle layer of watery tears secreted by accessory lacrimal glands in the conjunctiva and an oily superficial layer secreted by the meibomian glands along the lid margin. Recent studies have shown that the mucous layer is the major constituent. It maintains even wetting of the ocular surface; the watery layer provides oxygen and nutrition to the conjunctiva and corneal epithelium and the oily film retards evaporation and maintains the optical integrity.

The examination of patients with ocular surface disease includes an assessment of dynamic lid function—lagophthalmos (defective lid closure), eyelid blinking or abnormal lid architecture—and an inspection of the whole conjunctival and corneal surface should be carried out. Frothy tears indicate excessive meibomian gland secretion, which may destabilize the tear film.

Fig. 5.29 The adequacy of the precorneal tear film may be judged qualitatively by the presence of excess debris or mucus, a decrease in the marginal tear meniscus and a shortened break-up time of the fluorescein-stained tear film.

Fig. 5.30 Schirmer’s test is useful in documenting tear production, although the results cannot always be correlated to symptoms. In the absence of local anaesthesia, a normal value is greater than 6 mm at 5 min.

Fig. 5.31 Dessicated epithelium stains with Bengal Rose dye; the degree of staining can be used to grade the severity of epithelial disturbance on the medial and lateral conjunctiva and cornea.

Adapted from A J Bron, Doyne Lecture. Reflections on the tears. 1997; 11:583–602.

KERATOCONJUNCTIVITIS SICCA

Tear film deficiency is a balance between the relationship of deficient secretion and evaporation. Keratoconjunctivitis sicca is a common cause of chronically irritable sore eyes that usually occurs in late middle-aged and elderly women owing to a gradual reduction in lacrimal secretion. Similar symptomatology and findings may be present in other conditions in which other components of the normal tear film, such as mucus and meibomian lipid, are reduced or absent. Dry eyes have a deficient or unstable tear film which contains mucus and debris and has a poor or absent meniscus at the lid margins. In severe cases, filaments of mucus can be seen attached to the cornea; these exacerbate the symptoms. Apart from idiopathic keratoconjunctivitis sicca, similar changes are seen with rheumatoid arthritis, Sjögren’s syndrome, sarcoidosis and localized conjunctival disease caused by trauma, infection or drugs. A particular feature of dry eye disease is the disparity between the severity of symptoms and the apparent lack of abnormal signs.

Fig. 5.32 The clinical picture of keratoconjunctivitis sicca shows diffuse punctate epithelial erosions over the lower one-third of the corneal epithelium that stain as red spots with Bengal Rose. The staining usually extends on to the lower bulbar conjunctiva in the exposure area. In this patient there is some associated conjunctival hyperaemia.

Fig. 5.33 In severe keratoconjunctivitis sicca, threads of dried mucus and epithelial cell debris become attached to the corneal epithelium. This condition is known as filamentary keratitis. Bengal rose stains mucus and devitalized cells; in this example it is seen staining the filaments more avidly than fluorescein, which has also been instilled. Filamentary keratitis produces severe discomfort and photophobia. Treatment lies in tear film augmentation and topical mucolytic agents.

By courtesy of Professor R J Buckley.

Fig. 5.34 The commonest association of keratoconjunctivitis sicca is rheumatoid arthritis. Among sufferers of the disease, 15 per cent may be expected to develop dry eyes, although usually not severely. This example shows the changes associated with advanced rheumatoid arthritis of the hands including the swollen metacarpophalangeal joints, ulnar deviation, swan-neck deformities of the fingers and the skin changes associated with vasculitis and steroid therapy.

SJÖGREN’S SYNDROME

Sjögren’s syndrome is typically seen in elderly women and is characterized by a combination of dry eyes, dry mouth and, frequently, rheumatoid arthritis. Patients should also have a serum autoantibody screen which is positive for the extractable nuclear antigens SS-A and SS-B.

Fig. 5.35 This patient illustrates the typical changes of dry eyes and mouth associated with Sjögren’s syndrome. Patients also have a small but statistically significant risk of developing a lymphoma. Mild cases respond to treatment with wetting agents. Occlusion of the lacrimal puncta by plugs or cautery alleviates symptoms in the more severe cases.

Fig. 5.36 A biopsy of the lip mucosa confirms the diagnosis of Sjögren’s syndrome by demonstrating a chronic inflammatory infiltration of the labial accessory salivary glands.

By courtesy of Dr P H McKee.

SUPERIOR LIMBIC KERATOCONJUNCTIVITIS

Superior limbic keratoconjunctivitis is an ocular surface disorder in which the predominant changes occur in the superior limbus and tarsal conjunctiva. Most cases are associated with a history of dysthyroid eye disease although the precise pathogenesis remains uncertain as some patients have no other associated pathology. It is possible that changes in intraorbital pressure or defective blinking due, for example, to upper lid retraction produce a mechanical alteration in the normal lid–globe interaction leading to surface cell damage of the conjunctiva and upper cornea that is best demonstrated by staining with Bengal Rose. The symptoms of ocular discomfort can usually be relieved by wetting agents.

Fig. 5.37 This patient, who had previously been treated for thyrotoxicosis, presented with a history of sore eyes for many months. There is some lid oedema and lid retraction.

Fig. 5.38 Rose bengal drops have been instilled into both eyes, which demonstrate the characteristic upper limbal staining from the 10 o’clock to the 2 o’clock positions in each eye. Typically, there is bilateral involvement which is best seen in the position of downgaze. The changes are more marked in the left eye, where a diffuse limbal infiltration extends on to the cornea and upwards on to the bulbar conjunctiva.

Fig. 5.39 This patient demonstrates a less severe example in which the changes are limited to scattered punctate staining of the limbus associated with mild hyperaemia. Examination of the superior tarsal conjunctiva shows mild hyperaemia and some papillae.

NEUROTROPHIC KERATITIS

Fig. 5.40 Neurotrophic keratitis results from partial or complete corneal denervation. Soon after denervation the surface epithelial cells of the cornea and conjunctiva lose their microvillae which hold the mucin layer of the tear film. The tear film becomes unstable because of the nonwetting surface and the eye is very vulnerable to infection and minor trauma. In this example there is a shallow ulcer due to loss of epithelium and the surrounding epithelium is grey and unstable. Botulin toxin-induced ptosis, a gold weight in the upper lid or a permanent tarsorrhaphy may prove necessary for corneal protection.

Fig. 5.41 Neurotrophic keratitis is a particularly severe problem when sensory V nerve lesions are combined with the motor deficit from a lower motor neurone VII palsy. A common cause is a cerebellar pontine angle tumour such as an acoustic neuroma.

SOLAR AND CLIMATIC EXPOSURE

Excessive exposure to outdoor conditions, and especially ultraviolet radiation, is associated with degenerative conjunctival changes that produce an irritable eye from tear film disturbance and localized inflammation. Translucent deposits can be seen in the corneal stroma. (See also Fig. 6.44.)

Fig. 5.42 Pingueculae are raised yellowish patches that enlarge gradually until they abut the cornea but do not encroach upon it. Histologically they are formed by elastotic degeneration of collagen within the substantia propria.

Fig. 5.43 A pterygium is a raised triangular area of bulbar conjunctiva that grows over the superficial cornea and produces visual symptoms either from direct encroachment on the pupil or from irregular astigmatism. Pterygia normally occur on the nasal bulbar conjunctiva. This is thought to be caused by the cornea focusing on lateral light from the temporal side on the nasal limbus damaging the nasal limbal stem cells. In temperate climates pterygia progress only very slowly and rarely cause visual symptoms but in sunny, hot, dusty regions of the world they can represent a serious threat to vision. Examination of the leading edge and body of the lesion shows whether the pterygium is active by the degree of vascular engorgement in the bulk of the lesion. These pterygia are quiescent: the eye is white, they are not inflamed and the vessels in the lesion are not engorged. Surgical removal is indicated if visual impairment is threatened or if the lesion causes discomfort but the recurrence rate is high, particularly if solar exposure continues. Postoperative recurrence can be reduced by using a conjunctival graft.

Fig. 5.44 Histological examination shows that the pterygium consists of hyalinized subepithelial collagen with elastotic degeneration. At the apex of the pterygium on the cornea there is fragmentation and destruction of Bowman’s layer. Similar, but less vascular, changes are seen in a pinguecula (which probably represents the initial stage of the disease).

NUTRITIONAL XEROPHTHALMIA

Nutritional xerophthalmia is one of the two main clinical manifestations of vitamin A deficiency. Vitamin A is a fat-soluble vitamin found in eggs, heart and liver which in humans can also be synthesized from the carotenoids found in yellow and green vegetables. Night blindness is the first sign of deficiency. About five million children suffer from xerophthalmia due to vitamin A deficiency annually with 250000 becoming blind. Ironically, this condition is common in areas where vegetables containing carotenoids are plentiful but not eaten for social or economic reasons. It usually affects children below 4 years of age who have stopped breastfeeding. Protein and caloric deficiency and secondary systemic and ocular infections compound the vitamin deficiency leading to a high mortality rate from bowel and respiratory infections.

Fig. 5.45 In the vitamin A-deficient eye there is a drying and wrinkling of the conjunctiva associated with the development of Bitot’s spots. These spots are small, white, cheese-like patches which may have a foamy appearance and do not wet easily. At this stage a punctate keratopathy may also appear.

Fig. 5.46 This photograph shows a late stage in the development of vitamin A deficiency in which the corneal epithelium is lost over the lower nasal part of the exposed eye. Note the dry, wrinkled conjunctiva.

Fig. 5.47 In advanced keratomalacia the whole cornea becomes softened and opaque. At this stage, the clinical picture is often complicated by secondary infection; in this case, secondary infection has resulted in perforation of the globe and endophthalmitis.

By courtesy of Dr A Sommer.

Fig. 5.48 The histological appearance of the conjunctiva in advanced keratomalacia shows thickened keratinized epithelium. Goblet cells are lost

By courtesy of Dr A Sommer.

DISEASES OF THE SCLERA AND EPISCLERA

The most common and important forms of scleral disease are the inflammatory disorders of scleritis and episcleritis. The sclera is composed of collagen and elastic fibres, and is subject to the range of disease processes that affect connective tissue elsewhere in the body—hence its association with chronic inflammatory joint disease and the vasculitides such as rheumatoid arthritis, Wegener’s granuloma, SLE, polyarteritis nodosa and polychonditis. The episclera (Tenon’s capsule) acts analogous to a synovial membrane for smooth movement of the eye. It has a fibroelastic connective tissue structure covering the sclera and carries a vascular network that consists of a deep and a superficial plexus. Scleritis is always accompanied by overlying episcleritis.

Fig. 5.49 The vascular supply of the anterior episclera and sclera are best examined at the slit lamp. The importance of understanding the vascular anatomy lies in the clues that it provides in differentiating the clinical patterns of inflammation with episcleritis and scleritis. Three layers of vessels are visible. The conjunctival plexus is the most superficial layer and can be distinguished clinically by its ability to be moved over the underlying structures. The superficial episcleral plexus is a radially arranged series of vessels within Tenon’s capsule that anastomose at the limbus with the conjunctival vessels and the underlying deep episcleral plexus that is closely applied to the sclera. The vessels in this layer are arranged in an irregular, reticular, nonradial fashion and, unlike the conjunctival and superficial layers, are not blanched by a drop of 1:1000 epinephrine.

EPISCLERITIS

Episcleritis is a benign self-limiting inflammation that occurs in young adults. It may be bilateral. The presenting features are acute redness and mild discomfort with occasional watering. Severe pain and photophobia are not characteristic features and, if present, suggest scleritis. Episcleritis is transient, recurrent and nondestructive. Most patients have no associated systemic disease but episcleritis may be associated with allergic, infectious or drug-related diseases sometimes with seronegative arthropathies and vasculitic diseases. Episcleritis may be diffuse or nodular, the latter form tends to be more symptomatic. Treatment with topical steroids or nonsteroidal agents is effective in shortening the duration of the condition.

Fig. 5.50 Diffuse episcleritis may affect a sector or the whole anterior segment of the globe. In this example the radial superficial episcleral vessels are dilated and, although there is some associated engorgement of the conjunctival and deep episcleral plexus, there is no scleral swelling or oedema.

Fig. 5.51 In nodular episcleritis the oedema and infiltration of the episclera are localized to one or more sites with engorgement of episcleral vessels around a central pale nodule. The nodules are mobile over the underlying sclera, they are not really tender and there is no scleral oedema. Resolution of nodular episcleritis tends to occur more slowly than in diffuse episcleritis and topical steroids or nonsteroidal anti-inflammatory drugs may help.

Fig. 5.52 The conjunctival vessels and superficial episcleral vessels can be blanched by a drop of 10% phenylnephrine or 1:1000 epinephrine, which is useful in differentiating scleritis from episcleritis as the deep episcleral plexus and the scleral oedema are seen more easily. The superficial episcleral plexus has a radial distribution; this is helpful in distinguishing the vascular changes of episcleritis from the more net-like deep episcleral plexus.

SCLERITIS

Scleritis, unlike episcleritis in which resolution takes place without damage, is a potentially destructive disease. Four clinical types are recognized: diffuse anterior, nodular anterior, necrotizing anterior with or without inflammation (scleromalacia perforans), and posterior scleritis. Scleritis causes redness, watering and photophobia but is distinguished from episcleritis by pain which may be severe. There is dilatation and engorgement of the deep episcleral plexus which is displaced forwards by scleral oedema. The lesions are tender to touch and usually have a purplish tinge because of venous engorgement. Deep episcleral biopsies (which are not without risk) show scleritis to be an immune-mediated vasculitis; necrotizing vasculitis is the result of fibrinoid necrosis of the vessel wall, thrombotic vascular occlusion and chronic inflammation. All scleritic lesions need to be examined for areas of capillary closure which is the earliest sign of necrosis. The majority of patients with necrotizing scleritis have an underlying identifiable causative systemic factor as do one-third of patients with the diffuse form of the disease. Necrotizing scleritis is associated with such diseases as rheumatoid arthritis, systemic lupus erythematosus, Wegener’s granuloma, polyarteritis nodosa, relapsing polychronditis and Crohn’s disease.

Diffuse and nodular anterior scleritis usually responds to systemic therapy with nonsteroidal anti-inflammatory agents such as flurbiprofen, although systemic steroids may be required for severe cases. Topical steroids may provide symptomatic relief but do not affect the underlying disease process. After resolution, increased transparency of the sclera and thinning of the collagen network can be seen.

Fig. 5.53 Diffuse anterior scleritis is the commonest and least severe form of scleritis accounting for up to 50 per cent of cases. It can be widespread or confined to one quadrant.

Fig. 5.54 A small number of patients may progress to necrotizing changes with repeated attacks. This patient with rheumatoid arthritis shows active scleritis with scleral thinning. The eye is dry with mucus in the tear film and a small area of central corneal ulceration stained with fluorescein.

Fig. 5.55 Nodular anterior scleritis is the second most common type of scleritis. It may appear to be similar to nodular episcleritis on superficial examination but the nodules are tender, associated with scleral swelling and cannot be moved over the tissues. Initial attacks resolve without scleral destruction but about 20% of patients progress to necrotizing disease with repeated attacks.

Fig. 5.56 Histological examination of an enucleated eye showing a granulomatous nodule in the equatorial sclera.

Fig. 5.57 Necrotizing anterior scleritis is the most serious form of scleritis and is usually very painful. The first indication of necrotizing change is vaso-occlusion or venular shutdown in areas of scleral inflammation. These areas are pale, even though the eye still appears congested. Vascular closure is followed by scleral thinning and bluish changes or scleral infarction when the affected area becomes white and sloughs. Unless the scleritis is adequately and promptly treated the condition will progress with increasing tissue destruction and potential loss of the eye. The management of these patients is difficult as they are often ill from systemic disease and the side-effects of treatment. High-dose oral or intravenous steroids are needed and cyclosporin, methotrexate or cyclophosphamide can be effective in recalcitrant cases. This patient shows an area of vascular closure that progressed to necrosis and ulceration 10 days later.

Fig. 5.58 Necrotizing anterior scleritis without inflammation, also known as scleromalacia perforans, is characterized by painless progressive thinning of the sclera in the absence of symptoms and with minimal inflammatory signs as a result of arteriolar occlusion of the deep episcleral vascular network. Pathologically there is infarction and sequestration of the affected area. It is nearly always associated with severe long-standing seropositive rheumatoid arthritis. In this example, the scleritis has resulted in conjunctival ulceration and guttering of the adjacent cornea, possibly as a dellen.

Fig. 5.59 Patients with scleromalacia perforans usually have severe long-standing rheumatoid arthrits. This patient (the same one as in Fig. 5.58) has a left 12 th nerve palsy from cervical arthritis.

Fig. 5.60 After resolution of an anterior diffuse necrotizing scleritis in a patient with Wegener’s granulomatosis, the eye shows scleral thinning. On slit-lamp examination, rearrangement of the remaining collagen bundles can be seen with changes in the vascular pattern over the lesion and at the limbus.

Fig. 5.61 Scleral thinning allows the dark choroidal pigmentation to be seen. Staphylomas usually result from raised intraocular pressure in the presence of scleral thinning. Perforation of the globe is rare in the absence of trauma.

Fig. 5.62 In this patient keratitis involves the whole circumference of the peripheral cornea (top left). Corneal stromal melting can be seen on lateral gaze (top right). With resolution of inflammation following systemic immunosuppression, an epithelialized peripheral corneal gutter persists (left).

Fig. 5.63 Sclerokeratitis may complicate an anterior scleritis when a diffuse peripheral opacity can be seen in the adjoining corneal stroma. In active disease, the whole thickness of the corneal stroma adjacent to a patch of scleritis may melt and ulcerate. Impending perforation may require a tectonic peripheral corneal transplant. This type of active limbitis is often accompanied by an acute rise in intraocular pressure and KP on the adjacent corneal endothelium.

Fig. 5.64 The diagnosis of posterior scleritis is frequently overlooked. The patient presents with ocular pain and visual loss from exudative retinal detachment, macular oedema or disc swelling. Although some patients have anterior involvement, inflammatory signs may be minimal and apparent only if the posterior sclera is examined by getting the patient to look in extreme gaze. With severe inflammation, there may also be proptosis and extraocular muscle involvement and the differentiation from orbital myositis or pseudo-tumour becomes difficult and perhaps academic. Fundus examination of a relatively mild case here shows slight optic disc swelling and subretinal fluid producing macular folds.

Fig. 5.65 B-scan ultrasonography is the most effective way of diagnosing the condition by demonstrating thickening of the sclera and separation of the episclera as a result of the inflammation. Exudative retinal detachment can also be detected by this method.