Ординатура / Офтальмология / Английские материалы / Pediatric Opthalmology_Mukherjee_2005

Complication of corneal fistula are :

1.Endophthalmitis, panophthalmitis due to introduction of infection.

2.Phthisis due to persistent hypotony.

3.Epithelial down growth.

Summary of perforation of corneal ulcer :

1.Small perforation with mobile iris. Adherent leucoma.

2.Moderate perforation with miotic pupil and mobile iris—corneal staphyloma.

3.Large perforation not closed by iris - Extrusion of intraocular content, lens and vitreous resulting in phthisis bulbae.

4.Small central perforation not plugged by iris - Corneal fistula.

5.Small central perforation sealed without incarceration of iris—anterior polar cataract.

Corneal opacity45, 46. Most of disorders of cornea result in loss of corneal transparency that may be short lived or permanent. Latter are due to fibroblastic reaction of various layers of cornea during healing and cicatrisation. Corneal opacities vary in number from single to multiple, their size also range from pinpoint to covering whole of the cornea. They are of different shape, and depth. According to depth of opacity, they are graded as nebula, macula, leucoma and leucoma adherent. Corneal opacities may be localised to cornea only or may be associated with disorders of other structures like uvea, lens and sclera. Secondary glaucoma is very common associated disorder with large corneal opacities. Difficulty in measurement of tesion over a scarred cornea is difficult, hence glaucoma is invariably missed. Presence of circumciliary congestion with opacity denotes presence of active uveitis or secondary glaucoma.

Corneal opacities can be unilateral or bilateral. One eye may show denser or more numerous opacity than the other.

Causes of cornal opacity :

1.Commonest cause of corneal opacity is replacement of transparent keratocytes by opaque fibrocytes as seen following keratitis, corneal ulcer and trauma. Bowman’s membrane and Descemets membrane once destroyed do not regain transparency.

2.Edema of cornea. It could be epithelial, stromal, endothelial or combined.

3.Inflammatory infiltration.

4.Vascularisation. Superficial or deep vascularisation always leave scar of obliterated vessels.

5.Degeneration of cornea. Band keratopathy is more common in children than in adults.

6.Dystropies of cornea. Many of corneal dystrophies manifest in childhood.

7.Deposits on cornea. Tattoo, corneal mucus plaque.

8. Encroachment of conjunctiva on cornea :

(i) Epithelial surface. Pterygium, pseudo pterygium, conjunctival hood flap, dermoid.

(ii) Endothelial surface. Epithelial down growth.

9.Blood staining of cornea

10.Pigment deposit. Generally not seen in childhood.

11.Folds in Descemets membrane

12.Rupture and splitting of Descemets membrane.

Symptoms. Symptoms of corneal opacities depend upon their position in relation to pupil. Central opacities even of fainter density may produce pronounced diminished vision that may lead to intractable amblyopia, nystagmus, squint. Peripheral corneal opacities do not produce diminished vision. However a peripheral opacity may be associated with irregular astigmatism. Other symptom is cosmetic blemish, the parents become aware of the opacity and the child may be brought solely for it, not realising that the opacity is also causing diminished vision. Simple corneal opacities are painless and the eye is white.

Signs. Only sign of simple corneal opacity is loss of corneal transparency without any evidence of inflammation. Corneal opacities do not stain with fluorescein. However facets in corneal opacity may retain dye without staining. In leucoma adherent, iris is either incarcerated in the opacity or there is evidence that the iris was entrapped in the past in the form of iris pigment in the white opacity. Other signs of leucoma adherence are irregular pupil, key hole pupil, irregular AC, may have anterior polar cataract. Occasionally vessels may grow into an opacity. Corneal sensation is generally absent or very poor over the opacities.

Management :

1.Best management is prevention. This is better said than done. Small Pox used to be one of the commonest causes of ugly corneal opacities before the disease was eradicated. Children not immunised against small pox were always at risk of developing corneal complications and children who were immunised never developed small pox related corneal opacities.

However vitamin A deficiency remains a formidable cause of preventable corneal opacity in children in underdeveloped countries. Compulsory oral administration should form a part of immunisation in children. Moreover adequate vitamin A also reduces severity of measles and malaria which indirectly lead to malnutrition. All children with trauma should receive prompt local antibiotic drop. Early and proper management of corneal ulcer reduces severity of opacity. In fact aim of treatment of corneal ulcer should be to give a transparent cornea as far as possible.

2.Definitive treatment for corneal opacity is keratoplasty, Lanellar or penetrating depending upon depth of the opacity. Superficial small opacities can be ablated by laser.

In failed penetrating keratoplasty or thick opacity where keratoplasty is not possible keratoprosthesis may be tried.

3.Optical iridectomy does not seem to do any good to the patient. Similarly tattoo replaces a white opacity with a dark deposit and is aesthetically not acceptable.

(ii) Bacterial infection over viral infection, reverse is rare. (iii) Bacterial superimposition on fungal ulcer.

(iv) Bacterial ulcer may be primary.

(v) Corneal pathogen or opportunistic organism which remain dorment without ulcer formation may become active due to loss of resistance of the cornea.

(vi) The corneal resistance is compromised due to immunosuppression by way of use of steroids, local anaesthetic, cytotoxic drug, broad spectrum antibiotic, and loss of corneal sensation.

Chief causes of central corneal ulcers are :

1.Bacterial. Pneumococcas, pseudomonas, streptococcus, Klebsiellapneumonae, staphyloccous.

2.Fungal

3.Viral

4.Keratoacanthamoeba

5.Keratomalacia.

Peripheral corneal ulcers. These ulcers are less vision threatening. They rarely perforate, most of them are painful. They are generally due to acute or chronic bacterial conjunctivitis but they themselves are not infectious. No organism is grown from corneal scrapping from these ulcers. They are due to sensitization to bacterial products. In these cases antibodies from limbal vessels react with corneal antigen to produce keratitis. They develop few millimetres inside the limbus as infiltrates that in duecourse ulcerate. Marginal ulcers are generally self limiting but recurrent. They respond well to local steroids. However peripheral herpes simplex and pseudomonas ulcer should get special attention.

Important Bacterial Central Corneal Ulcers

1. Pneumococcal ulcer47, 48. Pneumococcus is by far the commonest cause of central corneal ulcer in all ages. Many strains of pneumococci cause corneal ulcer. Commonest strain is type IV but infection by type III cause more complication than any other form. It has a short incubation period (24-48 hours) following injury, which may be very mild. The ulcer to begin with is central, disc shaped, grey white in colour. The ulcer has a tendency to spread both towards the periphery and penetrate deep. This tendency to creep has been called Acute serpiginous ulcer. The ulcer creeps in one direction and heal in the area away from the advancing edge. The ulcer has tendency to change direction. Pneunococcus is a common inhabitant of normal conjunctiva. The cornea gets infected only following epithelial damage. Chronically inflamed lacrimal sac acts as a reservoir of organism. Pneumococcal corneal ulcer is associated with moderate to severe mucopurulent conjunctivitis. Uveal reaction is always severe resulting into moderate to big hypopyon that is produced due to toxin of the organism, hence the hypopyon is sterile. The hypopyon does not get organised and remains fluid.

Management49, 50. Scrapping from the active edge promptly grow Gram positive, diplococci. Occasionally the organism can be seen in short chain. Generally there is a capsule surrounding each pair. The organism should be cultured and its sensitivity to various antibiotics

graded. The pneumococci is known to become resistant to antibiotics specially penicillin. Generally systemic antibiotics are not recommended unless patient has systemic involvement. Systemic antibiotic should be administered in full dose in consultation with physician. All cases of pneumococcal keratitis threatening to perforate should also get systemic antibiotic. Usually available commercial ophthalmic drops are not sufficient for management of suppurative keratitis. Fortified aqueous drops should be administered frequently. Frequency may be as often as every five minutes for six times followed by every ten minutes for another six times. This is followed by hourly instillation during day and two hourly at night. Commonly used fortified drops are :

Penicillin G—100,000 1u/cc Bacitracin—10,000 IU/cc Cefazolin—50 mg/c.c.

Other antibiotics used are erythromycin, vancomycin. Ciprofloxacin is less effective.

If topical antibiotic drops are not effective or there is a moderate hypopyon concurrent sub-conjunctival injection of either 0.5 to 1.0 milli units of penicillin or 50mg to 100mg of cefazolin BD may evert further extension.

As there is always associated severe uveitis, use of atropine is one of the most important steps in suppurative keratitis. Atropine is administered as one percent ointment two times a day. It is better to avoid atropine as drops in children because there is always danger of atropine drop being instilled in dose more than therapeutically permitted. The eye should be bandaged at night only if there is no discharge.

Pseudomonas keratitis46, 48, 51. Pseudomonas aeruginosa causes one of the most serious central corneal ulcers and is one of the most common causes of perforating corneal ulcer. The organism is an opportunistic, gram negative, mobile, obligate aerobe that produces a proteolytic enzyme which acts on stroma and is responsible for early perforation. About 5% of population pass pseudomonas in stool and yet be asymptomatic. Common mode of infection are - instillation of contaminated fluorescein or anaesthetic drops in hospitals or by contaminated contact lenses specially extended wear. It has also been cultured from contact lens solutions. Pseudomonas has a short incubation period. Otherwise it may follow mild trauma.

Pseudomonas corneal ulcer starts as a small central area of infiltration following trivial injury and spreads in all directions. Occasionally it may start in the periphery. The ulcer spreads rapidly, is always associated with severe pain. Hypopyon develops fast and increases with spread of ulcer. Hypopyon has greenish blue hue due to pigment produced by the organism. Pseudomonas ulcer may spread so fast as to cause large central perforation within twenty four hours. Ulcer is always associated with mucopurulent conjunctivitis that may have satellite conjunctival abscess. Peripheral ulcers may spread into the sclera as tunnel lesions. All fast spreading corneal ulcers in contact lens users should be considered to be due to pseudomonas unless proved otherwise by culture.

Management of pseudomonas ulcer does not differ from any other central ulcer. When pseudomonas is suspected but its presence has not been confirmed a combination of fortified cepfazolin and tobramycin should be used as drops very frequently. Once

Traditionally type I herpes simplex is said to involve the body above the waste and type two is said to effect below waste (genital herpes). However, infection above waste by type two and infection below waste by type one is also known. Both types infect skin, mucousmembrane, mucocutaneous junction and cornea. Herpes keratitis is ocular counterpart of labial herpes and dendritic ulcers resembles fever blister. Though typical lesions of herpes simplex render their diagnosis easy specially in epithelial lesions. Chronic lesions may simulate many other lesions. In chronic lesion superimposed secondary infection change the clinical presentation grossly.

Clinically there are two types of herpes simplex infection :

1.Primary infection is the infection that develops in person who has not been exposed to HS virus earlier. Unfortunately primary infection is almost universal and may be symptomless. 90% of adult population is sero positive for HSV. Children suffer from HSV can be divided into three groups -

Primary infection by type I does not occur in children under six months of age due to maternal immunity passed to a child unless infected during birth from infected maternal birth canal. HS infection may prove to be fatal in neonates. Commonest mode of presentation in new born is milder form of non-gonococcal ophthalmia neonatorum.

2.The next age group that develop primary HSV infection is after six months of age when maternal antibodies disappear. This age group spans between six months to 10 years children in this group get infected by virus shed from lesions on the lips, lids even genital of adults.

3.Third age group comprise of sexually active adults and adolescent.

Primary herpes simplex infection of the eye and the adnexa consist of - Lid vescicles, blepharitis, lymphadenopathy, follicularconjunctivitis, pseudo membranous conjunctivitis, keratitis, micro dendrile, dendrile, and mild kerato uveitis. Neonates have severe iritis. Primary lesions are generally self limiting.

Recurrent herpes simplex infection of cornea is seen in persons who have been exposed to primary infection. The lesions are mostly central but can be peripheral as well that are more difficult to manage.

Following primary infection, the virus gains access to the central nervous system and remains dormant in trigeminal or spinal ganglion only to be reactivated by some catalyst (trigger mechanism) like stress, ultra violet ray, fever, menses, systemic infection, general anaesthesia, food allergens etc., resulting into lesions of skin, lips, mouth and followed by corneal lesion. However some of the corneal lesions are independent of trigger mechanism.

In recurrent lesions active viruses travel down the nerves to infect the target organ that develop classical lesions.

Corneal lesions can be : 1. Epithelial, and 2. Stromal.

1. Epithelial lesions are54

1.Dendritic ulcer or micro dendrite

2.Geographic (amaeboid)

3.Metaherpetic keratitis

Dendritic ulcer is typical of herpes simplex infection of cornea. Initially it may be present as smaller micro dendritic ulcer in the epithelium, in the centre of cornea, less commonly on the periphery. The dendritic ulcer has an irregular linear shape from which branches sprout and progress while the older part of the ulcer heals by epithelial slide. New defects develop on the progressive branch that may form terminal bud. The bed of the ulcer stains with fluorescein and the edges and terminal buds stain with rose bengal. Corneal sensation is dull which masks the pain sensation, preventing the patient from an early consultation. However only symptom may be lacrimation and foreign body sensation, some conjunctival congestion. In the initial stage, there may be no circumcorneal congestion, the vision may be good to begin with.

Other epithelial lesion that may be caused by HSV are blotchy epithelial keratitis, satellite epithelial keratitis, and rarely filamentary keratitis. They may precede to formation of dendritic ulcer or may co-exist with it to be transformed into typical dendritic ulcer.

Subepithelial opacities may develop under the original epithelial defect in the form of ghost image. The shape of which is identical to original dendritic ulcer but larger. The ghost image may last as long as one year. They may become worse by use of anti viral drugs specially idoxuridine.

As ninety five percent of HSV keratitis are unilateral, all cases of unilateral watering of short duration, without any definite history of trauma, or foreign body in the cornea or upper tarsal conjunctiva should be stained and examined under cobalt blue light for ulcer. Staining should be preceded by examination of corneal anaesthesia.

Other causes of formation of dendritic ulcers are :

Herpes zoster, corneal abrasion, Thygeson’s keratitis and contact lens.

Gepgraphic (amoeboid) ulcer. If dendritic ulcer does not heal it spreads in all direction to form a geographic or amaeboid ulcer that stains with fluorescein. Commonest cause of geographic ulcer is fast growth of virus on the periphery due to compromised immunity of cornea especially following indiscriminate use of local steroid or cytotoxic drugs. Vision is hampered as the epithelial defect is large and covers the pupillary area.

Metaherpatic keratitis. These are non viral component of dendritic and geographic ulcer due to problem of healing at the level of damaged basement membrane. They are caused by corneal denervation, they are trophic, indolent in nature. These ulcers last for long time with very little inflammatory reaction. The lesions heal with continuously worn therapeutic contact lens, prolonged pad and bandage, use of lubricants.

Stromal involvement. Stromal involvement is commonest complication of recurrent HSV keratitis. It is generally preceded by recurrent attack of dendritic or geographical ulcer. It is commonest cause of diminished vision that is more pronounced than in epithelial keratitis because healing of stromal keratitis is always associated with stromal scarring. Uveal

involvement is universal in stromal involvement. There may be vascularisation, stromal necrosis, and perforation.

Various types of stromal involvement are :

Necrotising keratitis is cause by active replication of virus in the lesion. It is an active stromal infiltrative process that may develop with or without epithelial defect. Stroma becomes necrotic with cheesy appearance. It is associated with anterior uveitis with keratic precipitates, just under the infiltration. There is no hypopyon. Presence of hypopyon is associated with secondary infection. Vascularisation and scarring are common. Necrosis of stroma may lead to perforation.

Disciform keratitis is an example of non necrotising deep keratitis. It is an antigen antibody reaction, generally associated with local or systemic immuno suppression that is produced following use of strong chemical to cauterise the ulcer, use of strong steroid, or iodoxuridine. There is a localised area of stromal edema generally in the centre of cornea.

The epithelium over the stromal thickening is elevated. There may be an endothelial defect just under the stromal thickening. Large white KP are very common just beneath the edematous area which is circular as the term disciform suggests. There may be folds in Descemet’s membrane. It is always associated with anterior uveitis. IOP may be raised. The condition is self limiting, it may take few weeks to resolve. Even when it resolves, it leaves a ring shaped opacity that represent the periphery of the lesion.

Complications of herpes simplex keratitis are :

Anterior uveitis, secondary glaucoma, complicated cataract, deep vascularisation of cornea, scleritis, corneal scarring, trophic ulcer, perforation.

Management of HSV infection of cornea :

Herpes simplex keratitis is said to be a self limiting disease, it takes weeks to month for both epithelial and stromal disease to heal, recurrence keratitis makes prognosis poor. Secondary bacterial and fungal infection are potentially dangerous. Condition becomes worse with indiscriminate use of steroid. Strong chemical cautery, loss of sensation are important causes of perforation. HSV infection does not impart local or systemic immunity. There is no known method of immunisation.

Aim of treatment is :

1.Eliminate virus by anti viral drugs - local or systemic.

2.Management of associated uveitis and glaucoma.

3.Judicious use of weak steroid for stromal involvement.

4.Protect the hyposthetic cornea from physical, chemical and microbial onslaught.

5.Increase local and systemic immunity.

6.Keratoplasty.

Antiviral agents used in HSV keratitis52, 53, 54, 55, 56

1. Idoxuridine. This is a thymidine analog. It is used as 0.1% drops or 0.5% ointment. It is effective in epithelial lesions both primary and recurrent. It does not penetrate the stroma and is insoluble in water, hence it has little use in stromal involvement. It is used in dendritic and geographical ulcers. Its main drawbacks are—insolubility in water, local epithelial toxicity and development of resistance, hypersensitivity, development of superficial punctate keratitis. Idoxuridine is used as 0.1% drops every hourly by day and two hourly by night for five days with 0.5% ointments three times a day. It may have to be used for two to three weeks. It is better to discontinue the drug after three weeks due to its corneal toxicity.

Trifluridine (Trifluorothymidine) is also an analog to thymidine. It inhibits DNA both in virus as well as host. It is used as 1% clear solution. It is used against both primary and recurrent HSV virus. It is more effective than idoxuridine and vidarabine. It is less toxic than the two. It is effective in stromal keratitis as well. Cross resistance with other antiviral drugs do not occur. It is used as nine times a day for ten days.

Vidarabine. This is an adenosine analog, a DNA inhibitor of both virus and host cell. DNA inhibition in host cell is less marked than in virus. It is available as 3% ophthalmic ointment to be used five times a day for five days. It is effective against epithelial keratitis. Treatment is not extended beyond three weeks for fear of corneal toxicity, which is however less than met with idoxuridine. Is is as effective as idoxuridine. Sometimes it is effective when idoxuridine is ineffective. It is less effective than trifluridine.

Acyclovir. This is an analog of guanosine. It stops viral replication. It is highly effective against type I and type II HSV. It is used against primary, and recurrent keratitis both epithelial and stromal.

It is available as 3% ophthalmic ointment, oral tablet and IV infusion. It is less toxic than idoxuridine and vidarabine. Ointment is used five times a day for five to seven days in adults.

Famciclovir. It is a pro drug with action similar to aclycovir. Usual dose in herpes simplex is 250 mg orally three times a day for seven days. It may be used as prophylaxis as 125 mg two times a day for one year.

Valaciclovir. Usual oral adult dose is 1 gm two times a day. It can also be used for prophylaxis in half the strength for one year. It is mostly used in treatment of herpes zoster.

All oral antiviral drugs should be used in consultation with pediatrician when used under 12 years of age.

2. Other non antiviral drugs used in management of HSV keratitis :

(i) Cycloplegic. Cycloplegics play an important role in management of viral keratitis. They have no action of virus multiplication or healing. They are essential in treating associated anterior uveitis which is inevitable in stromal keratitis. They also abolish pain of cyclospasm associated with epithelial defect.