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Continuing Education & Training<br />

Roger J. Buckley MA, FRCS, FRCOphth, HonFCOptom<br />

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Module 8 Part 5<br />

Therapeutics in<br />

clinical practice<br />

About <strong>the</strong> author<br />

Roger Buckley is Professor of<br />

Ocular Medicine, Department of<br />

Optometry and Visual Science,<br />

City University, and Honorary<br />

Consultant Ophthalmologist at<br />

Moorfields Eye Hospital, London.<br />

Therapeutics in practice<br />

Disorders of <strong>the</strong> conjunctiva – Part 1<br />

The conjunctiva is a mucous membrane, which in its normal state,<br />

is difficult to visualise as it is thin and transparent.<br />

Conjunctivitis is an inflammation of <strong>the</strong> conjunctivae, which<br />

usually affects both eyes at <strong>the</strong> same time – although it may start in<br />

one eye and spread to <strong>the</strong> o<strong>the</strong>r after a day or two. It may be<br />

asymmetrical, affecting one eye more than <strong>the</strong> o<strong>the</strong>r.<br />

There are many causes of conjunctivitis and<br />

<strong>the</strong> management will depend on <strong>the</strong> cause.<br />

The most frequent are bacterial or viral<br />

infection, and allergic or toxic reactions.<br />

However, it is important to note that <strong>the</strong>re<br />

are many o<strong>the</strong>r causes (Table 1).<br />

Fur<strong>the</strong>rmore, it is important to distinguish<br />

secondary conjunctivitis (e.g. secondary to<br />

a disorder to <strong>the</strong> surrounding tissue, or<br />

o<strong>the</strong>r causes of red eye, Table 2) from<br />

primary conjunctivitis. The most frequent<br />

causes of red eye include subconjunctival<br />

haemorrhage, blepharitis, dry eye and<br />

minor ocular trauma. Appropriate<br />

history taking and clinical examination<br />

will enable <strong>the</strong> practitioner to differentiate<br />

between <strong>the</strong>se and more serious disease and<br />

secondary conjunctivitis.<br />

1 CET point Infective Bacterial<br />

Viral (adenoviral & o<strong>the</strong>rs, herpes simplex and herpes zoster)<br />

Chlamydial<br />

Allergic and toxic Seasonal (hayfever) and perennial<br />

allergic conjunctivitis<br />

Vernal keratoconjunctivitis<br />

Atopic keratoconjunctivitis<br />

Giant papillary conjunctivitis (CL related)<br />

Contact sensitivity and toxicity<br />

Inflammatory Reiter’s syndrome<br />

Oculocutaneous<br />

- Pemphigoid<br />

- Stevens-Johnson syndrome<br />

Parinaud’s oculoglandular syndrome<br />

Superior limbic keratoconjunctivitis<br />

O<strong>the</strong>r<br />

Conjunctiva<br />

Cornea<br />

Eyelids<br />

Lacrimal<br />

Tear film<br />

Intraocular<br />

Sclera and episclera<br />

Orbital<br />

Artefacta (self-induced)<br />

Idiopathic (unknown cause)<br />

Subconjunctival haemorrhage<br />

Foreign body (e.g. subtarsal)<br />

Conjunctival neoplasm (cancer)<br />

Corneal foreign body<br />

Corneal abrasion<br />

Marginal keratitis<br />

Microbial keratitis<br />

Herpes simplex keratitis<br />

Table 1<br />

Causes and types of primary conjunctivitis<br />

Blepharitis<br />

Trichiasis (in-turning lashes)<br />

Entropion and ectropion<br />

Abnormal lid closure (exposure) e.g. lid paralysis<br />

Molluscum contagiosum (sheds irritant virus into tear film)<br />

Chronic infection of a blocked nasolacrimal system<br />

Dry eye<br />

Iritis, uveitis<br />

Acute glaucoma<br />

Scleritis<br />

Episcleritis<br />

Orbital cellulitis<br />

Dysthyroid eye disease<br />

Table 2<br />

O<strong>the</strong>r causes of a red eye<br />

30 | May 6 | 2005 OT

Continuing Education & Training<br />

Mechanisms of<br />

conjunctival inflammation<br />

Inflammation is <strong>the</strong> pathological process by<br />

which white blood cells and fluid<br />

accumulate within a tissue. It is<br />

characterised by pain, redness, swelling,<br />

heat and resulting loss of function. These<br />

features, which are regarded as classic and<br />

cardinal, are mediated by specific<br />

pathophysiological reactions, each of which<br />

is characterised by complex interactions<br />

between cellular effectors and chemical<br />

mediators.<br />

Pain is produced by <strong>the</strong> stimulation of<br />

nerve endings. Redness and heat result from<br />

dilatation of small blood vessels and<br />

accelerated metabolism. Swelling is caused<br />

by <strong>the</strong> accumulation of extracellular fluid,<br />

fibrin and inflammatory cells. All of <strong>the</strong>se<br />

changes toge<strong>the</strong>r impair <strong>the</strong> normal<br />

functions of <strong>the</strong> inflamed tissue.<br />

Three mechanisms that can initiate<br />

inflammation are infection, immune<br />

response and trauma.<br />

Infection<br />

Most infections, of <strong>the</strong> eye as well as of<br />

o<strong>the</strong>r tissues, cause inflammation. However,<br />

a few do not, for example, latent infection<br />

of <strong>the</strong> trigeminal ganglion by herpes<br />

simplex virus. In bacterial infection, cell<br />

wall components (endotoxins) of both<br />

gram-positive and gram-negative organisms<br />

trigger inflammatory reactions. A<br />

particularly powerful agent is bacterial<br />

lipopolysaccharide (LPS), a component of<br />

gram-negative bacterial cell walls. It activates<br />

<strong>the</strong> white blood cells, known as monocytes<br />

and polymorphonuclear leucocytes<br />

(‘polymorphs’) and causes <strong>the</strong>m to<br />

degranulate with resulting tissue damage.<br />

LPS also upregulates <strong>the</strong> activity of cellstimulating<br />

chemical mediators, known as<br />

cytokines, activates <strong>the</strong> complement cascade<br />

(a group of proteins present in blood<br />

plasma and tissue fluid which combine with<br />

an antigen/antibody complex to bring about<br />

<strong>the</strong> lysis of foreign cells), and injures <strong>the</strong><br />

endo<strong>the</strong>lium of small blood vessels so that<br />

<strong>the</strong>ir contents leak into <strong>the</strong> tissues.<br />

In addition to <strong>the</strong> harmful effects of<br />

<strong>the</strong>se endotoxins, bacteria can cause tissue<br />

damage via secretions known as exotoxins.<br />

Many of <strong>the</strong>se are enzymes, which cause<br />

damage to cell membranes, <strong>the</strong>reby<br />

initiating inflammation.<br />

Immune response<br />

Reactions between antigens and antibodies<br />

are powerful triggers to inflammation.<br />

Antigen-antibody complexes can ei<strong>the</strong>r be<br />

formed within <strong>the</strong> ocular tissues or<br />

deposited in <strong>the</strong>m from <strong>the</strong> general<br />

circulation. These immune complexes<br />

initiate inflammation by a number of<br />

mechanisms. They activate <strong>the</strong> complement<br />

pathway, which causes tissue damage by<br />

attracting white cells (chemotaxis). They<br />

also cause degranulation of specific cells,<br />

such as mast cells and basophils, with <strong>the</strong><br />

liberation of vasoactive substances which<br />

increase vascular permeability and obstruct<br />

blood flow by platelet aggregation. Some of<br />

<strong>the</strong>se products of degranulation, for<br />

example, eosinophilic major basic protein,<br />

are toxic to <strong>the</strong> ocular surface and are<br />

probably involved in <strong>the</strong> corneal epi<strong>the</strong>lial<br />

erosion that is typical of severe chronic<br />

allergic eye disease (vernal<br />

keratoconjunctivitis, VKC, and atopic<br />

keratoconjunctivitis, AKC).<br />

Ano<strong>the</strong>r type of immune mechanism<br />

involves T-lymphocytes, which mediate<br />

delayed hypersensitivity reactions. Some<br />

T-lymphocytes are cytotoxic; one of <strong>the</strong>se is<br />

<strong>the</strong> CD8 T-lymphocyte, which recognises<br />

infected host cells and destroys <strong>the</strong>m with<br />

minimal associated tissue damage. Viral<br />

infections are controlled in this way.<br />

Ano<strong>the</strong>r is <strong>the</strong> CD4 T-lymphocyte, which<br />

causes severe tissue damage in <strong>the</strong> course of<br />

eliminating <strong>the</strong> pathogen.<br />

Immediate hypersensitivity is ano<strong>the</strong>r<br />

cause of inflammation. In a sensitised<br />

individual, this process begins when an<br />

allergen (such as plant pollen or animal<br />

dander) enters <strong>the</strong> eye through <strong>the</strong> tear film<br />

and conjunctiva and bridges<br />

immunoglobulin E (IgE) receptors on mast<br />

cells. This causes degranulation of <strong>the</strong> mast<br />

cells with <strong>the</strong> release of vasoactive<br />

substances, including histamine, tryptase,<br />

and platelet activating factor. These<br />

substances initiate complex cellular and<br />

humoral mechanisms, which toge<strong>the</strong>r<br />

produce <strong>the</strong> symptoms and signs of allergic<br />

eye disease (for example, seasonal allergic<br />

conjunctivitis, SAC).<br />

Trauma<br />

Inflammation results from trauma of all<br />

kinds. Mechanical or chemical stimulation<br />

of sensory nerves produces vasodilatation<br />

and increased vascular permeability. Tissue<br />

damage, <strong>the</strong> introduction of infection and<br />

chemical injury all result in activation of<br />

cellular and humoral mechanisms, such as<br />

those already described. It should not be<br />

forgotten that surgery is a form of trauma<br />

and that <strong>the</strong> inflammation inevitably<br />

produced is potentially harmful, especially<br />

in <strong>the</strong> transparent ocular tissues where<br />

<strong>the</strong>re is a threat to vision. Such<br />

inflammation can be controlled by <strong>the</strong> use<br />

of steroidal or non-steroidal<br />

anti-inflammatory drugs.<br />

In <strong>the</strong> very rare condition of sympa<strong>the</strong>tic<br />

ophthalmitis, a perforating injury to one<br />

eye produces a granulomatous panuveitis<br />

in <strong>the</strong> fellow eye after a latent period. This<br />

is a predominantly T-lymphocyte<br />

modulated, delayed hypersensitivity<br />

reaction.<br />

Clinical signs of<br />

conjunctival inflammation<br />

The normal conjunctiva<br />

The conjunctiva is a mucous membrane.<br />

In its normal state, it is quite difficult to<br />

Figure 1<br />

Ciliary injection, that is, redness of <strong>the</strong> eye<br />

most marked around <strong>the</strong> limbus<br />

Figure 2<br />

Marked lid swelling, mild chemosis and a pink<br />

conjunctiva in seasonal allergic conjunctivitis<br />

(hayfever)<br />

visualise, being thin and transparent. Many<br />

of <strong>the</strong> blood vessels that are seen are, in<br />

fact, beneath it.<br />

Though <strong>the</strong> conjunctiva is a single<br />

continuous membrane, it is divided<br />

anatomically into three areas:<br />

• Bulbar (loosely covering <strong>the</strong> anterior<br />

part of <strong>the</strong> globe and fusing with <strong>the</strong><br />

cornea and sclera at <strong>the</strong> limbus)<br />

• Tarsal (tightly adherent to <strong>the</strong> upper and<br />

lower tarsal plates)<br />

• Forniceal (loosely lining <strong>the</strong> upper,<br />

lower, temporal and nasal fornices)<br />

In order to examine <strong>the</strong> lower tarsal and<br />

forniceal conjunctiva, <strong>the</strong> lower lid is<br />

pulled down and <strong>the</strong> patient is asked to<br />

look up. The upper tarsal conjunctiva is to<br />

be seen when <strong>the</strong> upper lid is everted.<br />

Double eversion of <strong>the</strong> upper lid brings <strong>the</strong><br />

upper forniceal conjunctiva into view.<br />

Hyperaemia<br />

Also called ‘injection’, this is redness of <strong>the</strong><br />

conjunctiva caused by dilatation of its<br />

capillaries. It may be generalised (‘diffuse’),<br />

as in viral or bacterial infection, or<br />

confined to <strong>the</strong> para-limbal area. This<br />

‘ciliary injection’ is seen in corneal<br />

infection and intraocular inflammation<br />

(e.g. uveitis), ra<strong>the</strong>r than in superficial<br />

infection (Figure 1). Localised hyperaemia<br />

may be caused by a patch of episcleritis or<br />

by <strong>the</strong> presence of an embedded foreign<br />

body.<br />

Chemosis<br />

Chemosis is visible oedema, or waterlogging,<br />

of <strong>the</strong> conjunctiva, which produces<br />

31 | May 6 | 2005 OT

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5<br />

Figure 3<br />

Gelatinous follicles in <strong>the</strong> interior fornix<br />

a blistered or ballooned appearance. It is<br />

due to <strong>the</strong> escape of serum from inflamed<br />

blood vessels into <strong>the</strong> conjunctiva and<br />

underlying tissues. It is seen in viral and<br />

bacterial infection and in allergic disease,<br />

such as SAC (Figure 2).<br />

Infiltration<br />

The term infiltration (or ‘cellular<br />

infiltration’) implies that inflammatory<br />

cells have been liberated into <strong>the</strong><br />

conjunctiva, and <strong>the</strong> result is loss of<br />

conjunctival transparency. In this situation,<br />

it is no longer possible to see <strong>the</strong> fine<br />

vessels underlying <strong>the</strong> tarsal conjunctival<br />

surfaces. Oedema, produced by <strong>the</strong> leakage<br />

of serum and protein, as well as<br />

inflammatory cells into <strong>the</strong> conjunctiva,<br />

contributes fur<strong>the</strong>r to <strong>the</strong> opacification.<br />

Sub-conjunctival haemorrhage<br />

A cause of ‘red eye’, this is usually a less<br />

dramatic event than its appearance<br />

suggests. Sub-conjunctival haemorrhage is<br />

usually spontaneous or <strong>the</strong> result of minor<br />

trauma and can happen in <strong>the</strong> normal eye.<br />

Occasionally, it results from hypertension<br />

or a bleeding disorder, and small patches of<br />

haemorrhage known as ‘petechial<br />

haemorrhages’ may be seen in viral and<br />

bacterial infection.<br />

Discharge<br />

Discharge commonly accompanies<br />

conjunctivitis. The discharge in allergic<br />

conjunctivitis and in viral infection is thin<br />

and watery. In chronic, severe allergic eye<br />

disease, <strong>the</strong> discharge is thick and stringy.<br />

In bacterial conjunctivitis, a purulent<br />

(pus-containing) discharge is common,<br />

which may have a yellow or greenish<br />

colour. This may dry on <strong>the</strong> lid<br />

margins and lashes overnight and<br />

cause <strong>the</strong> lids to be gummed toge<strong>the</strong>r on<br />

awaking.<br />

Follicles<br />

Follicles are typical of certain types of<br />

conjunctival inflammation. They are<br />

usually small, raised, whitish or pinkish<br />

lumps in <strong>the</strong> tarsal conjunctiva (Figure 3).<br />

There is normally no central blood vessel.<br />

Follicles consist of masses of lymphocytes,<br />

which have accumulated in response to an<br />

Figure 4<br />

Giant papillae, and a pale conjunctival<br />

scar under <strong>the</strong> upper lid in severe<br />

vernal keratoconjunctivitis<br />

immune reaction to viral or chlamydial<br />

infection. They are also seen in contact<br />

conjunctivitis and in staphylococcal<br />

blepharo-keratoconjunctivitis.<br />

Papillae<br />

Papillae are divisible into three types,<br />

according to <strong>the</strong>ir diameter (which can be<br />

measured using <strong>the</strong> length of <strong>the</strong> slit lamp<br />

beam):<br />

• 1mm: giant papillae (Figure 4)<br />

Micropapillae fall within <strong>the</strong> category of<br />

normality: a normal tarsal surface may be<br />

perfectly smooth or bear micropapillae.<br />

Macropapillae and giant papillae have<br />

similar histologies and pathogenesis and<br />

are <strong>the</strong> result of chronic inflammation,<br />

especially of allergic origin.<br />

Pseudomembrane<br />

Pseudomembrane is distinguished from<br />

true membrane (for example, that<br />

occurring in diph<strong>the</strong>rial infection) by <strong>the</strong><br />

fact that it can be wiped away from <strong>the</strong><br />

surface of <strong>the</strong> affected mucous membrane.<br />

Consisting of mucus, fibrin and<br />

inflammatory cells, it accumulates on <strong>the</strong><br />

tarsal surfaces in severe conjunctival<br />

infections, such as that sometimes<br />

produced by <strong>the</strong> adenovirus.<br />

Scarring<br />

Scarring can occur as a result of any chronic<br />

conjunctivitis. In trachoma, <strong>the</strong>re is<br />

cicatricial (shrinking) scarring which can<br />

produce entropion of <strong>the</strong> lid margins. In<br />

vernal keratoconjunctivitis, ano<strong>the</strong>r disease<br />

caused by chronic conjunctival<br />

inflammation, this process is not seen. At<br />

<strong>the</strong> slit lamp, scar tissue is sometimes more<br />

easily seen if <strong>the</strong> red-free (green) filter is<br />

used.<br />

Keratinisation<br />

This dysplasia of <strong>the</strong> conjunctiva is seen in<br />

a number of chronic inflammations, such<br />

as Stevens-Johnson syndrome and ocular<br />

cicatricial pemphigoid. The normally nonkeratinising<br />

conjunctiva begins to produce<br />

keratin, especially just inside <strong>the</strong> lid<br />

margins, and this comparatively rough,<br />

32 | May 6 | 2005 OT

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Figure 5<br />

Multiple small star-like subepi<strong>the</strong>lial corneal<br />

opacities in adenoviral infection<br />

Figure 6<br />

Molluscum contagiosum lesion on <strong>the</strong> lid margin<br />

skin-like, non-wetting surface can<br />

traumatise <strong>the</strong> ocular surface. Therapy with<br />

retinoic acid drops is sometimes prescribed<br />

for this condition.<br />

Bacterial infection<br />

Bacterial conjunctivitis is a common,<br />

usually self-limiting condition. The usual<br />

cause is a gram-positive infection<br />

(Staphylococcus epidermidis, Staphylococcus<br />

aureus, Streptococcus pneumoniae) but<br />

gram-negative infections (Haemophilus<br />

influenzae, Moraxella lacunata) are common<br />

also. Patients complain of a sudden onset<br />

of redness, watering and grittiness of <strong>the</strong><br />

eye, which may be sticky on waking. The<br />

condition causes discomfort but is not<br />

painful.<br />

Clinical signs:<br />

• Hyperaemic conjunctiva<br />

• Epiphora<br />

• Mucopurulent discharge<br />

• Vision is usually normal as <strong>the</strong> cornea is<br />

unaffected, though it may be<br />

temporarily obscured by discharge<br />

Management:<br />

• Topical antibiotic drops, e.g.<br />

chloramphenicol 0.5%, applied every<br />

two hours for two days, <strong>the</strong>n four times<br />

daily for ano<strong>the</strong>r three or four days<br />

• Topical antibiotic ointment, e.g.<br />

chloramphenicol 1%, can also be used,<br />

though it temporarily causes smeary<br />

vision if too much is instilled.<br />

Bacteriostatic tear levels are achieved<br />

more readily with <strong>the</strong> ointment than<br />

with <strong>the</strong> drops<br />

• O<strong>the</strong>r antibiotics that are commonly<br />

used include ofloxacin, gentamicin and<br />

fusidic acid<br />

Ophthalmia neonatorum can be contracted<br />

by <strong>the</strong> newborn during normal delivery<br />

when <strong>the</strong>re is infection of <strong>the</strong> birth canal.<br />

The usual agents are Chlamydia trachomatis<br />

and Neisseria gonorrhoeae. These can<br />

produce severe infections involving <strong>the</strong><br />

cornea as well as <strong>the</strong> conjunctiva, and<br />

require urgent management by an<br />

ophthalmologist.<br />

Viral infection<br />

Adenovirus<br />

Adenovirus infection is a common cause of<br />

acute epidemic keratoconjunctivitis,<br />

especially in <strong>the</strong> Summer months. It is<br />

highly contagious, being communicable for<br />

10 to 14 days with an incubation period of<br />

five to 12 days, and tends to proliferate in<br />

closed communities (e.g. schools, Summer<br />

camps, prisons) and in places where<br />

patients attend, such as eye out-patient<br />

departments and accident and emergency<br />

departments. Several strains of adenovirus<br />

may cause it; some are more virulent than<br />

o<strong>the</strong>rs and some produce a keratitis also.<br />

Though <strong>the</strong> portal of entry is <strong>the</strong><br />

conjunctiva, <strong>the</strong>re is commonly an<br />

associated upper respiratory tract infection,<br />

which may precede <strong>the</strong> conjunctivitis by a<br />

few days. Because <strong>the</strong> disease is so easily<br />

picked up, <strong>the</strong>re may be a history of o<strong>the</strong>rs<br />

in <strong>the</strong> family, class or workplace having<br />

been affected.<br />

Clinical signs:<br />

• Swelling of <strong>the</strong> lids<br />

• Follicular conjunctivitis, especially of<br />

lower fornix (easy to examine) and<br />

upper fornix (difficult to examine);<br />

usually one eye is earlier and more<br />

severely affected than <strong>the</strong> o<strong>the</strong>r<br />

• In severe cases, <strong>the</strong> tarsal<br />

surfaces may be covered by<br />

pseudomembrane<br />

• Swelling of pre-auricular and o<strong>the</strong>r<br />

local lymph nodes (lymphadenopathy)<br />

• Punctate epi<strong>the</strong>lial and sub-epi<strong>the</strong>lial<br />

keratopathy (requires slit lamp<br />

examination) (Figure 5)<br />

Management:<br />

• Specific anti-viral treatment<br />

is not yet available<br />

• Advise <strong>the</strong> patient that <strong>the</strong><br />

condition is highly contagious<br />

• Non-severe cases are best managed<br />

outside eye departments because<br />

of <strong>the</strong> infective danger to o<strong>the</strong>r<br />

patients and to staff<br />

• A topical steroid can be used in severe<br />

cases (pseudomembrane, sight-involving<br />

keratitis). Treatment should be initiated<br />

and monitored by an ophthalmologist.<br />

This may be required for weeks or<br />

months and steroid-related adverse<br />

effects may result<br />

Herpes simplex virus<br />

It is a common clinical impression that<br />

cases of herpes simplex keratitis are<br />

becoming less frequent. The primary<br />

infection may be a mild and transitory<br />

unilateral or bilateral blepharoconjuctivitis.<br />

Recurrent disease (usually unilateral) is<br />

more serious, as it involves <strong>the</strong> cornea. The<br />

virus resides in <strong>the</strong> trigeminal ganglion,<br />

from which it cannot be eradicated.<br />

Clinical signs:<br />

• Primary herpes: vesicles on lid margin,<br />

plus follicular conjunctivitis<br />

• Dendritic ulcer: a branching linear<br />

epi<strong>the</strong>lial ulcer of <strong>the</strong> cornea, easily seen<br />

if fluorescein is instilled into <strong>the</strong> tear film<br />

and <strong>the</strong> eye is examined with a blue light<br />

• ‘Amoeboid’ or ‘geographical’ ulceration<br />

involves <strong>the</strong> corneal stroma and is more<br />

severe. It may result from incorrect use<br />

of topical steroid<br />

• Scarring, vascularisation of <strong>the</strong> cornea<br />

with reduction of vision if <strong>the</strong> central<br />

area is involved (disciform keratitis)<br />

Management:<br />

• Topical <strong>the</strong>rapy with ophthalmic<br />

antivirals, such as aciclovir (Zovirax<br />

ophthalmic ointment)<br />

• Severe recurrent cases and bilateral cases<br />

may require systemic antivirals<br />

• If pseudomembrane is present, or if<br />

keratitis is severe or persistent, <strong>the</strong><br />

ophthalmologist may prescribe a topical<br />

steroid in conjunction with a topical<br />

antiviral<br />

• A low-dose topical steroid is required on<br />

a long-term basis in some cases, without<br />

antiviral cover. The lowest possible dose<br />

is always prescribed. Very low dilutions<br />

of prednisolone in drop form are<br />

available from some hospital pharmacies<br />

Herpes zoster virus<br />

Herpes zoster infection of <strong>the</strong> ophthalmic<br />

division of <strong>the</strong> trigeminal nerve (herpes<br />

zoster ophthalmicus) may involve <strong>the</strong><br />

anterior segment of <strong>the</strong> eye. Involvement of<br />

<strong>the</strong> nasociliary nerve, with skin lesions on<br />

<strong>the</strong> side or tip of <strong>the</strong> nose, makes this likely.<br />

Clinical signs:<br />

• Maculopapular rash over forehead<br />

• Conjunctivitis<br />

• Episcleritis<br />

• Punctate epi<strong>the</strong>lial keratitis<br />

• ‘Pseudodendrites’ of mucus (stain with<br />

rose bengal)<br />

• Nummular keratitis (cloudy stromal<br />

inflammation)<br />

• Disciform keratitis similar to herpes<br />

simplex keratitis<br />

• Associated with uveitis<br />

Management:<br />

• Systemic aciclovir<br />

• Systemic NSAID (e.g. flurbiprofen)<br />

for episcleritis<br />

• A topical steroid and antiviral (e.g.<br />

aciclovir ointment)<br />

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Molluscum contagiosum<br />

The characteristic small umbilicated skin<br />

lesions of molluscum contagiosum may<br />

occur on <strong>the</strong> lids (Figure 6). Viral particles<br />

shed from <strong>the</strong> surface of <strong>the</strong> lesions may fall<br />

into <strong>the</strong> tear film, causing a unilateral or<br />

bilateral follicular conjunctivitis.<br />

Management is by removal (incision and<br />

curettage) of <strong>the</strong> lesions. There may be<br />

lesions elsewhere on <strong>the</strong> body and it is<br />

important that all of <strong>the</strong>se be removed,<br />

o<strong>the</strong>rwise <strong>the</strong> condition will recur.<br />

Chlamydial infection<br />

Inclusion conjunctivitis<br />

In <strong>the</strong> West, chlamydial keratoconjunctivitis<br />

is most often seen as a sexually transmitted<br />

condition and as a cause of ophthalmia<br />

neonatorum. It is known as inclusion<br />

conjunctivitis because of <strong>the</strong> appearance of<br />

characteristic basophilic cytoplasmic<br />

inclusion bodies on Giemsa staining of<br />

conjunctival smears. The causative agent is<br />

Chlamydia trachomatis sub-group A,<br />

serotypes D–K.<br />

Clinical signs:<br />

• Follicular conjunctivitis<br />

• Punctate epi<strong>the</strong>lial keratitis<br />

• Urethritis, cervicitis<br />

Management:<br />

• Topical tetracycline ointment (currently<br />

difficult to obtain)<br />

• Systemic tetracycline, doxycycline or<br />

erythromycin, when genital infection is<br />

also present<br />

• Referral to <strong>the</strong> genito-urinary clinic or<br />

sexually-transmitted disease clinic<br />

Trachoma<br />

Trachoma, caused by Chlamydia trachomatis<br />

(sub-group A, serotypes A–C) is one of <strong>the</strong><br />

world’s most important causes of<br />

preventable blindness, and occurs in<br />

underprivileged populations, among whom<br />

it is spread by flies.<br />

Clinical signs:<br />

• Chronic follicular conjunctivitis<br />

• Conjunctival scarring leading to tear<br />

deficiency and entropion<br />

• Corneal scarring and vascularisation<br />

secondary to lid disease and tear<br />

deficiency (Figure 7)<br />

Management:<br />

• Avoidance of infection by improved<br />

personal hygiene<br />

• Drug <strong>the</strong>rapy as for inclusion<br />

conjunctivitis<br />

Recent experience in Tanzania has shown <strong>the</strong><br />

value of mass treatment of a population. The<br />

prevalence of trachoma before <strong>the</strong> start of<br />

<strong>the</strong> study was 9.5%. Systemic azithromycin<br />

was given to <strong>the</strong> population, followed by<br />

tetracycline eye ointment in persistent cases.<br />

Two months later, <strong>the</strong> prevalence was 2.1%<br />

and this had fallen to 0.1% at two years.<br />

Ocular allergic disease<br />

Because of its exposed nature, <strong>the</strong> mucous<br />

membrane of <strong>the</strong> eye comes into contact<br />

with a huge number and a wide variety of<br />

airborne particles. Allergic diseases of <strong>the</strong><br />

eye are responsible for a wide range of<br />

disorders, from <strong>the</strong> familiar and<br />

uncomfortable condition of SAC to rarer,<br />

life disrupting disorders, such as vernal<br />

keratoconjunctivitis.<br />

Six types of ocular allergic disease have<br />

been described:<br />

• Acute allergic conjunctivitis (AAC)<br />

• Seasonal allergic conjunctivitis (SAC)<br />

• Perennial allergic conjunctivitis (PAC)<br />

• Vernal keratoconjunctivitis (VKC)<br />

• Atopic keratoconjunctivitis (AKC)<br />

• Contact lens-associated papillary<br />

conjunctivitis (CLAPC) or giant<br />

papillary conjunctivitis (GPC)<br />

Table 3 shows <strong>the</strong> differences between <strong>the</strong><br />

six basic conditions in terms of age of<br />

onset, need of topical steroid medication<br />

and morbidity. An interesting feature is <strong>the</strong><br />

geographical variations between <strong>the</strong><br />

conditions; in Europe, mild conditions are<br />

common while severe sight-threatening<br />

conditions are rare.<br />

Acute allergic conjunctivitis (AAC)<br />

This urticarial reaction presents as<br />

conjunctival and lid oedema of sudden<br />

onset and can affect both atopes and nonatopes.<br />

It results from <strong>the</strong> introduction of a<br />

significant amount of allergen (e.g. pollen,<br />

animal dander) into <strong>the</strong> eyes. The eyes itch<br />

and <strong>the</strong> lids may swell to <strong>the</strong> extent that<br />

<strong>the</strong>y close.<br />

Clinical signs:<br />

• Oedema of bulbar conjunctiva<br />

• Swelling of lids, ptosis<br />

• No corneal involvement<br />

Management:<br />

• Self-limiting, usually requiring no<br />

treatment<br />

• If recurrent, attempt to identify <strong>the</strong><br />

allergen and counsel avoidance<br />

• If recurrent, consider treatment with<br />

topical mast cell stabilisers<br />

Seasonal allergic conjunctivitis (SAC)<br />

SAC is a common condition (also called<br />

hay fever conjunctivitis) affecting up to<br />

21% of <strong>the</strong> general population in <strong>the</strong> age<br />

group 10 to 40 years (peaking at 20 to 30<br />

years). It is <strong>the</strong> ocular component of hay<br />

Figure 7<br />

Progressive corneal scarring in AKC<br />

fever. The symptoms are itching, watering,<br />

stickiness and redness of <strong>the</strong> eyes, plus<br />

o<strong>the</strong>r symptoms of hay fever. It is<br />

important to ask <strong>the</strong> patient about his or<br />

her specific symptoms, as hay fever is<br />

variable in its manifestations.<br />

Clinical (ocular) signs:<br />

• Minimal conjunctival oedema and<br />

hyperaemia<br />

• Mild papillary hypertrophy of<br />

conjunctiva<br />

• No corneal involvement<br />

Management:<br />

• Allergen avoidance (which is difficult or<br />

impossible in <strong>the</strong> case of common<br />

allergens, such as grass pollen or house<br />

dust mite)<br />

• Topical mast cell stabilisers,<br />

e.g. sodium cromoglicate, lodoxamide,<br />

nedocromil sodium<br />

• Systemic anti-histamines, a number of<br />

which can be bought without<br />

prescription at pharmacies or even<br />

non-pharmaceutical retail outlets<br />

• Topical anti-histamines: guttae<br />

Otrivine-Antistin (a combination of<br />

vasoconstrictor and antihistamine) or<br />

modern H1-receptor antagonists, such<br />

as emedastine, azelastine, levocabastine<br />

and epinastine. Also mast cell<br />

stabiliser/antihistamine drugs such as<br />

olopatadine and ketotifen<br />

Perennial allergic conjunctivitis (PAC)<br />

PAC is less common than SAC; it occurs at<br />

any time of <strong>the</strong> year, with seasonal<br />

variation. In <strong>the</strong> UK, it is a response to <strong>the</strong><br />

presence of house dust mite (HDM). The<br />

symptoms are <strong>the</strong> same as for SAC and<br />

again <strong>the</strong> signs are minimal. Drug<br />

management follows <strong>the</strong> same principles.<br />

Patients need advice on <strong>the</strong> reduction of<br />

Table 3<br />

Summary of allergic eye disease – age presentation, need of steroid and morbidity<br />

Condition Age at presentation Need of steroid Morbidity<br />

AAC All ages although highest prevalence in children Nil Low<br />

SAC Between <strong>the</strong> ages of 10 and 40 years Nil Medium<br />

PAC As above Low Medium<br />

VKC Usually less than 10 years of age Very likely High<br />

AKC Young adults Very likely High<br />

GPC Any age group although highest Very low, except in Medium<br />

prevalence in contact lens wearers pros<strong>the</strong>sis wearers<br />

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Figure 8<br />

Epi<strong>the</strong>lial macro-erosion in VKC<br />

Figure 9<br />

Corneal plaque in VKC<br />

HDM levels in <strong>the</strong>ir environments,<br />

especially <strong>the</strong> bedroom. This will involve<br />

high levels of domestic cleaning, removing<br />

carpets and curtains where possible and<br />

covering mattresses and pillows with<br />

mite-proof covers. Syn<strong>the</strong>tic pillows<br />

that can be washed at 60˚C are to be<br />

preferred to pillows containing fea<strong>the</strong>r or<br />

down.<br />

Vernal keratoconjunctivitis (VKC)<br />

In <strong>the</strong> UK, this is a rare, serious disease of<br />

<strong>the</strong> young (incidence

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Module 8 Part 5 of Therapeutics in clinical practice – Disorders of <strong>the</strong> conjunctiva – Part 1<br />

Please note: There is only ONE correct answer<br />

1. Which one of <strong>the</strong> following<br />

statements is incorrect?<br />

Inflammation is:<br />

a. a process by which white blood cells<br />

and fluid accumulate within a tissue<br />

b. characterised by pain, redness, swelling,<br />

heat and resulting loss of function<br />

c. mediated by specific<br />

pathophysiological reactions<br />

d. initiated by infection only<br />

2. Which one of <strong>the</strong> following<br />

statements is incorrect regarding<br />

infection?<br />

a. Endotoxins trigger inflammatory<br />

reactions<br />

b. Lipopolysaccharide (LPS) is a<br />

component of gram-positive bacterial<br />

cell walls<br />

c. LPS activates white blood cells<br />

d. LPS upregulates <strong>the</strong> activity of<br />

cytokines<br />

3. Which one of <strong>the</strong> following<br />

statements is incorrect regarding<br />

<strong>the</strong> immune response?<br />

a. Immune complexes initiate<br />

inflammation by activating <strong>the</strong><br />

complement pathway<br />

b. Immune complexes cause<br />

degranulation of mast cells and<br />

basophils<br />

c. T-lymphocytes mediate delayed<br />

hypersensitivity reactions<br />

d. Immediate hypersensitivity<br />

involves IgG receptors<br />

4. Which one of <strong>the</strong> following<br />

statements is incorrect regarding<br />

hyperaemia?<br />

a. It is caused by constriction of<br />

capillaries<br />

b. It may be diffuse in viral or bacterial<br />

infection<br />

c. Ciliary injection is associated with<br />

corneal infection and intraocular<br />

inflammation<br />

d. Localised hyperaemia may be caused by<br />

a patch of episcleritis or an embedded<br />

foreign body<br />

5. Which one of <strong>the</strong> following statements<br />

is incorrect regarding sub-conjunctival<br />

haemorrhage?<br />

a. Occurrences are usually spontaneous<br />

b. It may result from hypertension or a<br />

bleeding disorder<br />

c. Petechial haemorrhages may be seen in<br />

viral and bacterial infection<br />

d. It is usually caused by major trauma<br />

6. Which one of <strong>the</strong> following statements<br />

is incorrect? Conjunctival discharge in:<br />

a. allergic conjunctivitis is thin and watery<br />

b. viral infection is thin and watery<br />

c. chronic severe allergic eye disease is<br />

thick and stringy<br />

d. bacterial conjunctivitis is thin and<br />

watery<br />

7. Which one of <strong>the</strong> following statements<br />

is incorrect regarding follicles?<br />

a. They are usually small, raised, whitish<br />

or pinkish lumps in <strong>the</strong> tarsal<br />

conjunctiva<br />

b. Usually <strong>the</strong>re is a central blood vessel<br />

c. Follicles consist of masses of<br />

lymphocytes<br />

d. They may be seen in staphylococcal<br />

blepharo-keratoconjuntivitis<br />

8. Which one of <strong>the</strong> following statements<br />

is incorrect regarding bacterial<br />

conjunctivitis?<br />

a. It is a common, usually self-limiting<br />

condition<br />

b. It is only caused by a gram-positive<br />

infection<br />

MCQs<br />

c. Patients complain of a sudden inset of<br />

redness, watering and grittiness of <strong>the</strong><br />

eye<br />

d. Vision is usually normal (occasionally<br />

obscured by discharge)<br />

9. Which one of <strong>the</strong> following statements<br />

is incorrect regarding adenovirus?<br />

a. It is highly contagious for 10 to 14 days<br />

b. Some strains may produce a keratitis<br />

c. An upper respiratory tract infection may<br />

precede <strong>the</strong> conjunctivitis<br />

d. Papillary conjunctivitis is an associated<br />

feature<br />

10. Which one of <strong>the</strong> following statements<br />

is incorrect regarding herpes simplex<br />

virus?<br />

a. The primary infection may be mild<br />

b. Recurrent disease may involve <strong>the</strong> cornea<br />

c. The virus resides in <strong>the</strong> trigeminal<br />

ganglion<br />

d. The virus can be easily eradicated from<br />

<strong>the</strong> body<br />

11. Which one of <strong>the</strong> following statements<br />

is incorrect regarding acute allergic<br />

conjunctivitis?<br />

a. It presents as conjunctival and lid<br />

oedema of sudden onset<br />

b. The eyes are itchy<br />

c. The cornea is usually involved<br />

d. The condition is usually self-limiting<br />

12. Approximately what proportion of<br />

vernal keratoconjunctivitis sufferers<br />

have a history of atopic disease?<br />

a. 15%<br />

b. 55%<br />

c. 75%<br />

d. 95%<br />

An answer return form is included in this issue. It should be completed and returned to:<br />

CET initiatives (c-133), OT, Victoria House, 178-180 Fleet Road,<br />

Fleet, Hampshire, GU51 4DA by June 4, 2005.<br />

Under no circumstances will forms received after this date be marked<br />

– <strong>the</strong> answers to <strong>the</strong> module will have been published in our June 6, 2005 issue.<br />

36 | May 6 | 2005 OT

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