Ординатура / Офтальмология / Английские материалы / Pediatric Opthalmology_Mukherjee_2005

more in under develop countries. The organism belongs to family paramyxo viridae and genus Morbilli virus. There is only one genetic type. Humans are the only natural host.

Systemic involvement

The disease is mostly seen in children between 6 months to 2 years. The disease spreads by droplet infection. The disease is most contagious from one to two days before the onset of symptoms and remains so for four days after the rashes have appeared.

The incubation period is of 10 days. The disease has following stages:

1.The prodromal stage

2.Stage of exenthema

3.Complications

In prodromal stage—There is fever, rhinitis, cough, Koplic spots in the buccal mucosa, and conjunctiva. The Koplic spots are blue-white spots against pink background.

In stage of exenthema, the body is covered with rashes. They last for 3-4 days and then disappear without leaving any scar.

The complications are related to respiratory system, central nervous system and GI tract. It is not uncommon for more than one system to be involved at the same time, which includes laryngitis, pneumonia, otitis media, deafness, encephalitis, gastroenteritis.

The ocular involvement

The conjunctiva is involved in prodromal stage and continues to be infected through the exanthematous stage. Commonest conjunctival involvement is catarrhal conjunctivitis, Koplic spot, swelling of plica, edema of lids. This is followed by severe photophobia due to epithelial keratitis. The cornea if infected by bacteria at this stage is bound to end in corneal ulcer, which may perforate if the child is malnourished with vitamin A deficiency. Other ocular manifestations are dacryocystitis15 and frequent stye.

The neuro ophthalmic complications due to measles are - Encephalopathy, that may lead to optic neuritis, papilledema, or paralytic squint.

Measles and vitamin A deficiency

Severity of measles is more in malnourished children. Death is more frequent in malnourished child. Children with borderline vitamin A deficiency develop night blindness and xerophthalmia soon. Measles itself can cause protein caloric malnutrition. It also depletes liver store of vitamin A.

Management

Prophylaxis—Measles is a fully preventable disease by live attenuated measles vaccine. All children between 6 months to 6 years should get oral vitamin-A 1,00,000 IU.

Systemic involvement—There is no specific antiviral drugs against measles. Only symptomatic and supportive treatment is required with a close watch on possibility of pneumonia, enchephalopathy and gastroenteritis which require special attention.

Ocular involvement is treated by local antibiotic, cycloplegic and non steroidal anti inflammatory drugs.

Once the child has been diagnosed to have measles, irrespective of his nutritional status, the child should get extra vitamin A. Common practice is to give 50,000 IU under six month, 100000 IU under one year and 200000 IU over one year in two equal divided doses.

Human immuno deficiency virus17,18

Human immuno deficiency virus contains RNA but no DNA. The virus uses hosts cellular mechanism to form DNA for its reproduction, depleting the immune system of the host. The human immuno deficiency virus type 1 (HIV 1) causes a multi systemic chronic contagious disease called acquired immuno deficiency syndrome (AIDS). It takes years to develop the systemic and ocular involvement in AIDS. Two third of the patients with AIDS will develop ocular symptoms. The condition is uniformly fatal. Presently available drugs do not change the immune deficiency but act against mostly the opportunistic organisms.

The disease is spread by body fluid. It is most commonly transmitted sexually. It can also be transmitted via infected blood products. The mother can pass the infection to the foetus via placenta. The neonate may acquire the disease during passage through infected birth canal. The breast-fed baby may get it from mothers’ milk. All body fluids including tears, aqueous, or saliva may be source of infection. Older children get infected either through infected blood products, infected needles or following sexual assault.

The HIV virus has affinity for CD4+ lymphocytes. The virus cripples the CD4+ cells, resulting in diminished and later deficient host immunity.

The diagnosis is confirmed when:

1.There is confirmed diagnosis of HIV I infection.

2.The CD4+ cell count is less than 200 cells/ mm3.

3.There is evidence of atleast one opportunistic infection.

4.There is some AIDS related malignancy.

The ocular infections are early to develop. The ocular lesions can be:

1.Retinal micro angiopathy

2.Ocular infection:

(i) Intra ocular (ii) Extra ocular.

By one or more opportunistic organisms

The opportunistic organism can be viral, bacterial or protozoal. More than one opportunistic infection may be present.

3.Uncommon neoplasms

4.Neuro ophthalmic complications

Retinal micro angiopathy is commonly known as HIV retinopathy, is the commonest ocular manifestation. The angiopathy is due to direct invasion of endothelium of the retinal vessels. The result is development of cotton wool spots, micro aneurysm, ischemic maculopathy. The lesions are produced by deposition of immune material in the vessels after the endothelium has been invaded by the virus.

Ocular infection

Intra ocular infection—Retinitis

Common opportunistic organisms are—Cytomegalovirus, herpes simplex, herpes zoster, toxoplasma, pneumocystiscarinii, mycobacterium, candida, and cryptococci.

Commonest and early intra ocular infection is cytomegalovirusretinitis (CNV). The virus is member of herpes family. The CNV affects neonates and adult immuno compromised patients. Almost one third of AIDS patients develop CNV in under developed countries where triple anti viral therapy is not available. The lesions develop along the retinal vessels due to invasion of the endothelium by the virus. The lesions are white granular dots. Superficial haemorrhage are common. Other findings are - Retinal edema, retinal vasculitis, and full thickness necrosis of the retina. The scattered spots, coalase to form larger area of necrosis that is replaced by gliosis. Posterior hole formations are common, leading to retinal detachment that is difficult to treat.

Early symptoms include diminished distant vision, floaters, central or ring shaped scotomas.

Treatment of CNV retinitis is difficult and costly. It includes IV ganciclovir for fifteen days followed by oral maintenance dose. Other mode of treatment is called highly active anti retro viral therapy (HART) which is a combination of anti retroviral drug and protease inhibitor. The anti retro viral drugs can also be given intra vitreous.

Progressive outer retinal necrosis (PORN)

This is rarer opportunistic infection in AIDS. It is caused by herpes zoster and other herpes simplex viruses. It starts as necrotising lesion of the peripheral retina that progresses relentlessly in circumferential fashion without involving retinal vessels. The condition is potentially blinding disease; about 80% of patients with PORN go blind inspite of treatment.

Uveitis

Multi focal choroiditis is caused by many organisms. The infection may be due to a single organism or a combination of organism like mycobacteriumtuberculosis, atypical mycobacteria, pneumocystitiscarinii, cryptococcus, toxoplasmosis. In contrast to multi focal choroiditis there may be solitary choroiditis due to syphilis which is not an opportunistic organism because those who develop syphilitic choroiditis have CD4+ cell count >200. It generally occurs in patients with neuro-syphilis.

The other intra ocular manifestations are non-granulomatous iritis, optic neuritis, retrobulbar neuritis, and papilledema.

Extra ocular involvement may be due to infection by opportunistic organism, neoplasm or CNS involvement.

They are:

Follicular conjunctivitis, keratitis, punctate or geographic that may look like herpes simplex keratitis.

Neoplasms associated with AIDS are:

Kaposis sarcoma, Burkitts lymphoma, squamous cell carcinoma of the conjunctiva.

Kaposis sarcoma is very aggressive neoplasm of endothelial cells. About one fifth of persons with AIDS develop Kaposis sarcoma, lesions of the skin of the lids are more common than conjunctiva. Orbital involvement is still rarer.

CNS involvement may cause encephalitis, meningitis, papillitis, papilledema, retrobulbar neuritis and extra ocular muscle palsy.

Smallpox virus (Variola)

Variola was a common, often fatal that left surviving children with life long scarred body and many a times blindness is no more seen. It has been eradicated in the year 1980 as a result of simultaneous global immunisation. It was a common cause of bilateral anterior staphyloma which can still be seen in patients in remote areas, who were borne before 1977, when the last case of small pox was seen.

Vaccinia

This is also a DNA virus that is closely related to smallpox virus but not identical to it. The two conditions have different presentation, mode of infection and host range. Vaccinia virus is used as prophylaxis against smallpox. Primary systemic vaccinia does not occur but is a distinct possibility. The vaccinia presents as auto inoculation, contact inoculation, complicated scar of vaccination and rarely vaccinia encephalopathy.

The lesion following auto inoculation or contact inoculation resembles single blister of small pox. The pastular lesion develops three days after vaccination; it can be anywhere on the body but more common on the face.

The ocular involvement is mostly in the lids. Less common are the conjunctival and corneal involvement. There is intense swelling of the lids, the preauricular lymph glands may be enlarged. It takes eight to ten days for the condition to subside.

Conjunctival lesion may be a pustule associated with purulent conjunctivitis. Pseudo membrane may form.

The cornea is involved secondary to lid lesion. It may be acute or chronic. The former is in the form of superficial punctate keratitis of mild nature that heals without any treatment unless contaminated by bacteria. The chronic form is a severe but rare disciform keratitis.

Rarely there may be iridocylitis and peri vasculitis. No specific treatment is required.

Herpes viruses

This group consists of herpes zoster, varicella (chicken pox), herpes simplex and cytomegalo virus.

Varicella (chicken pox). This is very common, benign, highly contagious disease of childhood seen world wide. Unlike small pox there is no universal immunisation against chicken pox.

The virus that causes chicken pox causes herpes zoster in adults. However it should be kept in mind that herpes zoster ophthalmicus is seen in pediatric age group as well. The virus, which is more commonly, called varicella zoster virus looks similarly to herpes simplex virus, but differs in chemical properties, antigenically and clinical presentation.

Systemic involvement

The chicken pox, which is an acute exanthematous disease spread by droplet infection. The incubation period is of 10-20 days. The patients are infectious two days prior to development of rashes. The patient remains infectious during the vesicle formation and during crusting.

The skin lesions are the most visible signs of the disease. The lesions begin as maculopapules, gradually going to vesicle that scab in about ten to fifteen days. The scabs fall leaving no permanent scar. The lesions can be seen on all exposed mucous membranes and skin. The skin lesions are associated with fever.

The complications arise if there is secondary bacterial infection superimposed, or the child is immune compromised. Extra cutaneous lesions are seen mostly in CNS in the form of meningeal irritation and ataxia. There may be meningitis, encephalitis, and transverse myelitis.

Varicella infection of the respiratory tract in the form of vericella pneumonia is most serious complication.

The ocular manifestations are—Vesicles may form on the lids and conjunctiva. Infection may spread to the lacrimal sac from conjunctiva or through nasopharynx. Chicken pox is a common cause of chronic dacryocystitis in children.15 Corneal involvement can occur at the vesicular stage as punctate keratitis or may develop disciform keratitis late.

Herpes zoster13, 19, 20

Herpes zoster is a sporadic disease mostly seen in adults but not an exception in children. Manifestation in children is milder and less painful. The disease in all ages in caused by same virus i.e. vericella herpes zoster virus. It is equally seen in both the sexes.

Herpes zoster is a unilateral disease. There is no predication for right or left side of the body. The virus involves one single dermatome at a time. Both cranial nerves and spinal nerves are involved. Simultaneous involvement of cranial and spinal nerve never occurs. The commonest dermatomes involved are T3 to L3. Commonest cranial nerve to be involved is trigeminal. Out of three divisions of fifth nerve, the 1st division is most commonly involved followed by maxillary. The third division is least involved. It is not uncommon to have involvement of only few branches of 1st division, commonest being supra orbital. The involvement of first division of the trigeminal is called herpes zoster ophthalmicus.

The infection starts most probably as varicella in the childhood and the organism lies dormant in the dorsal roof ganglion and manifests only when the organism is reactivated. Most of the patients do not have recent history of exposure. It is said that about 2 percent of patients may develop second attack of herpes zoster.19

The typical lesion develops as unilateral vesicular eruption along the dermatome anywhere on the body that may be painful or preceded by pain. Most of the lesions will be followed by post herpetic neuralgia that is more marked in adults. Older the patient greater is the pain, eruption in the distribution of cranial nerves is more painful than those of spinal nerves. The vesicular lesions look very similar to those of varicella. Generally it takes 7 to 10 days for the vesicles to crust and leave hypo pigmented shallow scars. There is hyposthesia along the dematome.

In herpes zoster ophthalmicus, the posterior roof ganglion involved is trigeminal ganglion. The geniculate ganglion is involved in Ramsay Hunt syndrome that includes— Vescicles in the external auditory canal, pain in the ear, loss of taste in the anterior two third of the tongue.

Most troublesome part of herpes zoster of spinal nerve is acute neuritis, result in pain, absence of touch sensation. This lasts for months to years.

Other complication are—Meningeal irritation and granulomatous angitis that may result in contra lateral hemiplegia, transverse myelitis and cranial nerve palsy otherthan the fifth and seventh.

Most important systemic complication of vericella herpes zoster virus infection is cutaneous dissemination where the skin lesions last for weeks. Other causes of dissemination are herpes zoster pneumonia and meningo encephalitis.

Ocular manifestation of herpes zoster21 is herpes zoster ophthalmicus (see page 52).

Some important points are:

1.Ten percent of all cases of herpes zoster infection are herpes zoster ophthalmicus.

2.Fifty percent of cases of herpes zoster ophthalmicus develop serious complication.

3.Ocular involvement is possible if maxillary branch is involved, may involve nasociliary nerve.

4.Lacrimal branch is generally spared.

5.Hutchinson’s sign is not a sure sign of corneal involvement.

6.Corneal hyposthesia even anaesthesia may develop and linger for years.

7.Anaesthesia dolorosa is common.

8.Lagophthalmos may develop in Ramsay Hunt syndrome.

9.Other extra ocular muscle palsy is possible which recover spontaneously in few months.

10.In acute stage mucopurulent conjunctivitis is common.

11.Corneal lesions are many. They may start as superficial punctate keratitis or micro dendrites; may become nummular or even disciform lesion may develop.

12.Episcleritis and scleritis are generally over shadowed by skin and conjunctival lesion.

13.Iridocyclitis is common.

14.Secondary glaucoma is frequent.

15.Optic neuritis has been reported frequently.

Herpes Simplex virus

Herpes simplex (HSV) infection is a world wide health problem that is seen in all ages including neonates, in both the sexes. About 90% of adults are sero positive for herpes simplex virus.

Herpes simplex virus is a complex DNA virus. There are two types of herpes simplex viruses i.e. type I and type II. The latter is also known as genital virus that can infect the eye.

It is acquired sexually and from the genitals spread to other parts of the body after a period of latency followed by reactivation. It can also involve the eye. The type I generally infects the body above waist. The lesions spread by infected saliva.

The infection is said to be primary when it develops in a non-immune person through infected secretions. It is generally acquired in early ages. The primary infection can be subclinical or clinical. The infection then travels to the sensory ganglion, serving the area of the primary infection i.e. trigeminal ganglion for HSV1 and spinal ganglion for HSV2.

The virus remains inactive in the root ganglion for variable time called latency, then following some trigger mechanism the virus travels down the axon to the target tissue and cause recurrent infection that keeps on recurring with period of apparent cure only to recur at irregular intervals.

The incubation period is 6 to 8 days. The infection starts either through mucous membrane or via an abraded skin. The foetus can get the infection via placenta in an infected mother. The neonate gets the infection from the birth canal of the infected mother.24

Systemic involvement depends on the type of the virus, i.e. type 1 or type 2, site of the primary lesion, target tissue, and immune status of the patient. Except for neonates, the herpes simplex virus is not a lethal virus. In immuno compromised especially in patients suffering from AIDS the organism behaves like an opportunistic organism and hasten the death.

The systemic involvement consists of:

1.Labial infection, vesicles on the lips or muco-cutaneous junction of the mouth

2.Infection of the upper respiratory passage i.e. pharyngitis, tonsillitis.

3.Upper GI tract—gingivitis, stomaititis, infection of hard pallet, tongue, soft pallet.

4.Genital infection

5.Infection of central nervous system

6.Infection of peripheral nervous system

7.Herpetic whitlow

Ocular manifestations are many, some of them are benign, others are potentially sight threatening.

They are:

1.Vesicles on the lid skin or at the junction of conjunctiva and skin. The vescicles that crust soon and heal without scar or loss of pigment. Sensation is normal.

2.Acute follicular conjunctivitis with enlargement of pre auricular lymph nodes. There may be pseudo membrane formation.

3.‘Keratitis—Epithelial : Half of the children develop superficial punctate keratitis scattered over the cornea. They become coarse within few days. This is followed by dendritic ulcer. The dendritic keratitis begins as coarse epithelial lesions in a linear form, which later develops branching. The branching is on one end, new lesions

develop at the terminal of the branching. The dendrite heals from one-end and progresses at the other end. The course of events may be one of the following:

(i) The dendritic ulcer heals within ten to twenty days with treatment, may even heal without treatment.

(ii) The dendritic figure expands in width and a geographic or amaeboid ulcer develops. Rarely the condition may pass into disciform keratitis.

(iii) Stromal Necrotic keratitis. This is due to invasion of the stroma by the virus. Some times the epithelium over the lesion may be intact. In majority of cases the epithelial defect persists.

(iv) Disciform keratitis. This may appear following dendritic ulcer or even without it. It is a hypersensitive reaction. The disciform lesion is central, oval diffuse.

It may be sub-epithelial lesion with stromal thickening surrounded by ring of infiltration. There may be folds in Descemet’s membrane. Anterior uveitis is common at this stage. The condition takes few weeks to months to clear.

5.Keratitis meta herpetica. This is not caused by viral invasion neither is an immune reaction. It is a persistent defect in the basement membrane.

6.Loss of corneal sensation is common. It starts from the stage of superficial punctate keratitis and lingers for months.

7.Uveitis is a common feature of HSV. It may be associated with keratitis at any stage or happen independent of keratitis. The uveitis is generally acute. That may lead to iris atrophy.

8.Secondary glaucoma is very frequently associated with HSV keratitis and uveitis and may be the cause of severe pain disproportionate to corneal lesion.

9.Superficial and deep vascularisation are common in long standing epithelial and stromal defects. (For details see chapter on cornea)

Cytomegalo virus

Cytomegalo virus is a DNA virus, morphologically similar to herpes simplex. The exact route of infection is not known. Percentage of persons with positive titer is high. It is estimated that about 4.5% pregnant women excrete virus in urine. The virus is also secreted in breast milk and saliva.

Systemic involvement

The condition can be congenital or acquired, can be seen in neonates or in adults. Immuno compromised person are very often infected by the virus.

The foetus gets the infection from the infected mother. The neonate can be infected during birth via infected birth canal.

Congenital CMV infection can be asymptomatic or the neonate may be seriously ill. Common features are under weighed child, microcephaly, hepatospleenomegaly, thrombocytopenia, patechial haemorrhage. There may be intra cranial calcification. There may be asymptomatic chorioretinitis.

Acquired CMV differs in presentation in immuno competent and immuno compromised.

In immuno competent, it presents as mono nucleosis, mostly in sexually active males. Incubation period is 20-60 days. There is fever with chills, body ache, headache, spleenomegaly; there may be pneumonitis.

CMV infection in immuno compromised person is a serious infection. It is a multi systemic disease.

Ocular manifestations is chorioretinitis. In neonates it is similar to toxoplasmic chorio retinitis. In AIDS, it is bilateral and extensive potentially blinding condition.

Molluscum contagiosum11,22,23

This is a DNA virus in the family of poxviridae. It has limited systemic involvement in normal healthy persons except the skin lesion which are self healing. In immuno deficient, it has prolonged course and the lesions are far more in number than in immuno competent. Its significance has increased since it has been observed to be too frequent in patients with AIDS.

The disease involves the skin mostly, however, the mucous membranes are also known to be involved.

The exact incubation period is not known. The commonest mode of spread is by direct close contact with the patient. The infection spreads to other parts of the body from the initial site by auto inoculation. Sexual transmission is also known. It is known to spread via swimming pools.

The typical lesion can be seen anywhere on the skin. Its number vary from a single lesion to few dozens. The lesion is a translucent or pearly growth few millimeters in diameter, raised, and circular in shape. The most striking feature is umblication in the center of the lesion. A caseous material can be expressed with pressure on the lesion. The expressed material is infectious. The lesions are also known to shed virus. The common sites are face, abdomen, back and groin.

It is a disease of childhood and adolescent; there is no immunity following initial infec-

tion.

The ocular manifestations are—Skin of the lids, lid margin, the lesion of lid margin causes chronic follicular conjunctivitis by the viruses shed from the lid lesion. The infection can spread from the conjunctiva to cornea in the form of kerato conjunctivitis.

The corneal involvement consists of punctate keratitis, pseudo dendrite, superficial pannus, and corneal ulcer. A limbal nodule may also develop. There may be notching up of the lid margin and scaring of the conjunctiva.

There is no specific treatment. The lesion are destroyed mechanically, chemically (tincture iodine or carbolic) by laser or cryo, only a few at a time. However patient with AIDS require intra venous cidofovir.

Chlamydiasis

Infection by chlamydia is very common. One of its manifestation trachoma is a major cause of preventable and treatable cause of blindness in a large part of the world. (See chapter on conjunctiva and cornea).

Chlamydias are a group of organism that are placed in between smallest bacteria and largest virus. It has a cell wall similar to bacteria. It possess both RNA and DNA. It is gram negative, obligate intra cellular organism. The organism is sensitive to many commonly used antibacterials but not to anti virals.

The organisms of chlamydia group are antigenetically similar. The three species are C trachomatis, C pneumoniae and C psittaci. The last one causes a rare form of respiratory infection that spreads from birds to men. The C pneumoniae is a frequent cause of upper respirator infection and pneumonia in children.

The organism C trachomatis is exclusively human pathogen and is the cause of trachoma, sexually transmitted diseases and infection in neonates.

Sexually transmitted Chlamydiasis

Genital infection is caused by C trachomatis, serovars D and K, generally known as genital trachoma.

Systemic involvements are:

In males, non-gonococcal urethrites. Common age group is late teens and early twenties. Many of them may be asymptomatic. In males it may cause epididymitis, Reiter’s syndrome, proctitis. In females it causes mucopurulent cervicitis, pelvic inflammation disease that includes salpingites, endometritis and infertility.

Inclusion body conjunctivitis of new born

Mucopurulent cervicitis in pregnant mother is the cause of neonatal inclusion conjunctivitis. It causes neonatal trachoma in about ten percent children born to infected mothers. Chlamydial inclusion conjunctivitis in children is replacing gonococci as main cause of ophthalmia neonatorum. Many a times it is difficult to differentiate between the two. Inclusion conjunctivitis develops five to fifteen days after birth while gonococcal infection has shorter incubation period i.e. one to three days. Gonococci stains grams negative. Intra epithelial inclusion cells are seen on Giemsa stain in inclusion conjunctivitis.

Inclusion body conjunctivitis in adults

The second peak of incidence is seen in late teens and early sexually active adults, following either direct infection of the eye or as finger to eye infection from infected genitals. Incubation period is 5-7 days.

The condition presents as mucopurulent conjunctivitis, generally unilateral with enlarged pre auricular glands. May spread to other eye after 5-7 days or more. The eyes may stick at night. There may be small area of superficial vascularisation of cornea. The conjunctivitis dies down over month without treatment, without scarring.

Management

Prophylaxis- All new born children should get one drop of 2% AgNO3 in each eye. It should be remembered that AgNO3 itself can cause self limiting chemical conjunctivitis. The better way is to instill 2.5% povidon in each eye. In absence of which any broad spectrum antibiotic drop may be used.

Once ophthalmia neonatorum has developed, it should be treated by standard method.