UVEITIES 

AND

 OCULARIMMUNOLOGY

The department of Uveitis and ocular immunology armed with three qualified consultants, a well equipped clinical laboratory and state of the art ophthalmic diagnostic equipment deals with the whole battery of ocular inflammations including autoimmune diseases and infections in both adults and children.
The Uveitis & Ocular Immunology Service provides a multidisciplinary approach to the treatment of ocular inflammatory disease and other infectious disorders. Experts here deal with diagnosis and management of complex infectious and autoimmune diseases of the eye as well as eye diseases associated with various other systemic medical disorders. The diagnostics are backed by a well equipped laboratory, pathology and molecular diagnostic services, and the consultants are conversant with appropriate intervention techniques. In addition we have the experience with the latest treatments including the use of immunosuppressive and immunomodulation for autoimmune eye diseases.
We co-ordinate with the other subspecialities of ophthalmology and internal medicine efficiently to get the optimal treatment outcomes for patients with complex Uveitic disorders. Another field of specialization is HIV/AIDS associated ocular infections wherein we have a combined experience of having seen over a few thousand HIV/ AIDS cases with ocular complications. We were the first in the world to have reported “Ocular Manifestations associated with Chikungunya fever” especially Chikungunya Retinitis. What is uveitis? Uvea is the middle part of the three coats of the eye. This further consists of the iris, ciliary body and the choroid. Inflammation of any of these parts is termed uveitis. What are the types of uveitis? Based on the part of the uvea involved, uveitis may be Anterior (involving the iris), Intermediate (involving the ciliary body), Posterior (involving the choroid) or Panuveitis (involving all the parts). What are the symptoms of uveitis? Symptoms of uveitis are highly variable and may include any of the following: redness, pain, watering, inability to see bright light, floaters, and / or decreased vision. What causes uveitis? Uveitis occurs as a result of an immune reaction by our body to antigens (substances our body considers foreign). This reaction may occur against infectious agents such as bacteria, fungi, viruses and even parasites. In a small subset of patients, uveitis can occur due to undeterminable causes. What investigations are uveitic patients required to undergo? Uveitic patients often require a whole battery of investigations in order that the underlying cause of uveitis be determined and hence appropriately treated. These usually include blood and urine tests and/ or X rays. At times, a sample of the fluid from the patients' eye may have to be subjected to lab tests. How is uveitis treated? Steroids are the mainstay of treatment in uveitis. Depending on the location and the severity of the inflammation, they are used in the form of eye drops, eye ointment, injections around/ in the eye or injectable / oral medications. Anterior (and intermediate) uveitis is treated with topical steroids along with dilating eye drops which help in reducing the pain associated with inflammation. These drops are to be used until the inflammation has completely subsided. The dose, strength and duration of the drops are determined by your doctor who decides the treatment in accordance to the amount of inflammation. Injection of the steroid around the eye (periocular steroids) is used in certain cases of intermediate uveitis (or in macular edema as a consequence of uveitis). This results in slow release of the drug over a period of three to four weeks. Injectable/oral steroids are often indicated in posterior/panuveitis.  Besides steroids, the other group of drugs used in the treatment of uveitis is immunosuppressives. These are especially reserved for patients intolerant to steroids, inflammation not resolving with only steroids and patients with certain systemic conditions like rheumatoid arthritis. The commonly used immunosuppressives include Methotrexate, Azathioprine, Cyclosporine , Mycophenolate mofetil, Cyclophosphamide and Biological agents. top What are the side effects of the drugs used in the treatment of uveitis? Both steroids and immunosuppressives have side effects that are often not serious and reversible following the discontinuation of the drugs. These drugs should always be taken as per your doctors' instructions. Never start or stop these drugs of you own accord. Topical steroids may cause cataract or an increase in the intraocular pressure (glaucoma). Oral steroids may cause acidity, increase in weight and rarely diabetes, hypertension, osteoporosis and nervousness/ depression. Immunosuppressives may cause bone marrow depression that is reflected as a decrease in your blood counts. Some of them also interfere with the normal functions of the liver, cause mouth ulcers, rarely sterility and secondary malignancies. Thus, periodic blood counts/liver function tests may be required and will be advised by your doctor when on these drugs. Women in the reproductive age group are advised not to become pregnant when on treatment with immunosuppressives/ steroids. If you develop any infection while on treatment you need to take appropriate antibiotics immediately after consulting your doctor. In case you require to undergo any surgical procedure while on these drugs, please inform your treating doctor about the same. Will uveitis recur after treatment? It is important to remember that uveitis is a recurrent condition and hence requires a prolonged and regular follow up with your doctor. Consult your ophthalmologist at the earliest signs of a recurrence. This will make treatment easier and resolution speedier. What are the complications of uveitis? Uveitic patients may develop cataract (opacification of the lens), glaucoma (raised intraocular pressure) and macular edema (swelling of the central part of the retina) in addition to the inflammation itself. These complications may require additional medical or surgical management.

Choroidal circulation related to myopic CNVMyopic choroidal neovascularisation (mCNV) may develop secondary to choroidal vascular insufficiency, according to a new study.High myopia is associated with excessive and progressive elongation of the globe, resulting in a variety of fundus changes that lead to visual impairment, including lacquer cracks in the Bruch membrane, choroidal neovascularization (CNV), and chorioretinal atrophy. The choroid is thin in highly myopic eyes and undergoes further attenuation with increasing age and increased myopia. Choroidal thinning may play a role in the pathophysiologic features of vision loss in high myopia. At some point relative ischemia of the outer retina, RPE, and the choroid itself may lead to pathologic decompensation.

Age related macular degeneration can

 be detected online:

age related macular degeneration, amd, wet amd, 

macular degeneration, neovascular membrane,

There are three distinct types of age related macular degeneration – nonexudative ("dry") and neovascular (exudative or “wet”).

• 
•  
•   >
•  
•  
•  
•  
•  
•  
•  
•  
•  
•  
•  
• Nonexudative 

Nonexudative type of age related macular degeneration show clumps of pigment in the outer retina and retinal pigment epithelium atrophy, macular drusen – usually bilateral.

• Neovascular.

Typical signs of neovascular age related macular degeneration are drusen and subretinal fluid or retinal pigment epithelium detachment associated with choroidal neovascularization. Sub-, intra-, or preretinal

blood, retinal exudates, pigment epithelium loss, subretinal angiomatous proliferation. Sometimes retinal angiomatous proliferation may precede the development of choroidal neovascularization and is characterized by focal teleangiectatic retinal retinal vessels with an adjacent superficial retinal

hemorrhage and associated intraretinal edema.

CHOROIDAL NEOVASCULARIZATION:

Neovascularization, Choroidal

Introduction
Background

This disorder describes the growth of new blood vessels that originate from the choroid through a break in the Bruch membrane into the sub–retinal pigment epithelium (sub-RPE) or subretinal space. Choroidal neovascularization (CNV) is a major cause of visual loss.
Pathophysiology

Mechanisms of CNV are not understood. Virtually any pathologic process that involves the RPE and damages the Bruch membrane can be complicated by CNV. Recently, a protein derived from the RPE, pigment epithelium derived factor (PEDF), was found to have an inhibitory effect on ocular neovascularization. Another peptide, vascular endothelium growth factor (VEGF), is a well-known ocular angiogenic factor.

The balance between antiangiogenic factors (eg, PEDF) and angiogenic factors (eg, VEGF) is speculated to determine the growth of CNV. VEGF has been temporally and spatially correlated with the development of CNV. Histopathologic specimens obtained from submacular surgery reveal the presence of VEGF in CNV. In addition, several researchers have induced CNV formation in animal models by overexpressing VEGF. Once secreted, VEGF binds to its receptors in endothelial cells activating several signal transduction pathways that end with the formation of a network of new vessels. As new choroidal blood vessels grow, they may extend into the sub-RPE space (Gass type 1) or into the subretinal space (Gass type 2). The location, growth pattern, and type (1 or 2) of CNV depend on the patient’s age and the underlying disease. Bleeding and exudation occur with further growth, accounting for the visual symptoms.
Frequency
United States

In the Wisconsin Beaver Dam Study, prevalence of CNV associated with age-related macular degeneration (ARMD) was 1.2% in adults aged 43-86 years. Myopia is the second most common cause of CNV in the United States and Europe. CNV is estimated to occur in 5-10% of myopes; 60-75% of these are subfoveal.

Disciform scars secondary to CNV from presumed ocular histoplasmosis syndrome (POHS) were present in 0.1% of people living in endemic areas. In multiple evanescent white dot syndrome (MEWDS), development of CNV is rare. In multifocal choroiditis, estimates of CNV range from 25-40% of patients. In punctate inner choroidopathy (PIC), 33% of patients develop CNV. Of these, 50% are subfoveal and result in visual acuities between 20/80 and 20/200.

CNV occurs in 5% of patients with birdshot chorioretinopathy. CNV occurs in virtually all choroidal ruptures during the healing phase; most involute spontaneously. In 15-30% of patients, CNV may recur and lead to a hemorrhagic or serous macular detachment with concomitant visual loss.

Mortality/Morbidity
ARMD is the most common cause of visual loss in people older than 50 years in the developed world. Up to 90% of visual loss in ARMD is secondary to CNV.
Myopia is the seventh greatest cause of registered blindness in the United States and Europe. CNV is responsible for most of this visual loss.
POHS is an uncommon cause of visual loss. Incidence and prevalence in the blind of Tennessee, an area endemic for histoplasmosis, were reported to be 2.8% and 0.5%, respectively.
Sex

No gender predilection exists.

Certain diseases (ie, choroidal ruptures, angioid streaks, myopic macular degeneration, multifocal choroiditis, PIC, MEWDS) that may be complicated by CNV have gender proclivity.

Age

CNV is associated with multiple ocular conditions, so the age distribution of CNV reflects the underlying condition.
For instance, younger patients are affected with POHS, multifocal choroiditis, MEWDS, and PIC.
Older patients will be affected by CNV secondary to ARMD.
Clinical
History
Painless loss of vision
Metamorphopsia
Paracentral or central scotoma
Apparent change in image size
Physical
Subretinal blood
Subretinal fluid
Lipid exudation
Retinal pigment epithelial detachment
Subretinal fibrosis (disciform scar)
Causes

Virtually any pathologic process that involves the RPE and damages the Bruch membrane can be complicated by CNV.

Degenerative conditions

ARMD
Myopia
Angioid streaks
Inflammatory or infectious conditions

Histoplasmosis
Sarcoidosis
Multifocal choroiditis
PIC
Choroidal tumors

Nevi
Melanoma
Hemangioma
Osteoma
Trauma

Choroidal rupture
Laser photocoagulation

FUCHES UVEITIES:

ochromic iridocyclitis, is

Fuchs’ heterochromic uveitis (FHU), sometimes known as Fuchs’ heter

a chronic (longstanding), relatively mild form of uveitis of unknown cause. . FHU is usually a

unilateral disease (affecting one eye) but in about 15% of patients both eyes are involved. FHU

typically presents as a chronic uveitis with change in the color of one eye compared to the other

(a phenomenon referred to as “heterochromia,” hence the name). FHU is commonly associated

with the development of a cataract and/or glaucoma.

History

FHU has been described in the medical literature since at least the 19

th

 century. The first

definitive characterizations and studies occurred in the beginning of the 20

th

 century by Professor

Earnest Fuchs from Vienna. Since then, many other ophthalmologists have added to our

knowledge of this condition.

Course of the disease

Many patients with FHU have no symptoms for many years. During that time, the eye shows

mild signs of inflammation if examined, but the patient may not notice pain or redness. ..

However patients may seek medical attention because of decreased vision, ‘floaters’ or a change

in the color of one eye. FHU may also be discovered during routine eye examination.

Patients with FHU may experience periods of relative inactivity of their disease alternating with

periods of activity and increased symptoms. In particular, patients tend to notice vitreous

opacities and floaters when their vitreous detaches from the surrounding retina, a condition

called posterior vitreous detachment (PVD). Once a PVD has occurred, the vitreous becomesvery mobile and its motion inside the globe casts shadows on the retina, perceived as "floaters".

Diagnosis and testing:

There is no laboratory test that can make the diagnosis of FHU. Rather, the clinical diagnosis is

based on the findings of a mild chronic uveitis in association with other characteristic changes in

the eye, including flattening and thinning of the iris which may sometimes, but not always, cause

heterochromia (Figure 1). If there is heterochromia, the affected eye may be lighter or darker

than the healthy eye. Other useful signs are the presence of inflammatory cells on the back

surface of the cornea (keratic precipitates). In FHU these keratic precipitates are distinct in their

appearance and distribution. Other types of uveitis may need to be ruled out, which is usually

done by careful history and the performance of laboratory testing.

Treatment:

Unlike most uveitis syndromes, FHU does not usually respond to corticosteroid treatment. Most

uveitis specialists avoid the long-term use of corticosteroids in FHU.

There are two conditions which may require medical and/or surgical treatment in FHU.

1. Cataract.  This  typically  presents  as  a  gradual  blurring  of  vision,  possibly

associated with glare while driving at night and difficulty reading. Cataract is

diagnosed on examination by an ophthalmologist. Cataracts may be removed

surgically  when  they  become  bothersome  to  the  patient  and  impair

performance of one’s activities of daily living.

2. Glaucoma. In most  cases, glaucoma does not  cause  symptoms in the  early

stages, and is only detectable by  examination. However, if undetected and

untreated,  glaucoma  causes  gradual  damage  to  the  optic  nerve  with

irreversible  loss  of  peripheral  (side)  vision.  Patients  with  FHU  should

therefore  be  examined  periodically  even  if they  notice  no  new symptoms.

Once  detected,  glaucoma  can  be  treated  medically  with  eye  drops  and

occasionally pills. Some patients require glaucoma surgery in order to control

the pressure inside their eyes and prevent visual field loss.

GLAUCOMA ASSOCIATED WITH UVEITIES

Glaucoma is an increasingly important cause of blindness as the world's population ages. Statistics gathered by the World Health Organization (WHO) in 2002 showed that glaucoma is the second leading cause of blindness worldwide, after cataracts. However, glaucoma presents perhaps an even greater public health challenge than cataracts because the blindness it causes is irreversible. Therefore, WHO officials are looking for ways to address the problems glaucoma causes.

In the United States alone, glaucoma has been diagnosed in more than 2 million people, who are at risk of becoming blind.

Glaucoma is statistically linked to elevated intraocular pressure (IOP), which is thought to be due to decreased flow of fluid (aqueous humor) from the eye. Treatments for decreasing IOP focus on either reducing the production of aqueous humor or on increasing the ability of the aqueous humor to drain from the eye. Treatments for reducing fluid production include the use of drugs to inhibit the production and the destruction of the ciliary processes that produce aqueous humor. These treatments are often ineffective at controlling IOP over many years.

Surgical techniques may be used to increase drainage. These techniques include using lasers (laser trabeculectomy) to treat the trabecular meshwork (the main drainage passageway), implanting artificial drainage valves, and surgically cutting additional passageways to drain the fluid. The image below depicts the traditional filtering surgery.

Risks associated with these surgical procedures include infection, cataracts, bleeding, and hypotony. Even if the surgery is initially successful, scarring may close the drainage channels at the surface layers in the course of months to years.

                    anterior uveities

infections with viruses of the family Herpesviridae are common worldwide. More than 100 herpes viruses have been characterized, but only 8 infect humans: Herpes simplex virus (HSV) 1 and 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpes virus 6-7-8. Those viruses can cause a wide spectrum of ocular disease, which comprises a number of clinical presentations: blepharitis, keratoconjunctivitis, dendritic epithelial keratitis, geographic or trophic herpetic corneal ulceration, stromal keratitis, and intraocular inflammation. Intraocular herpetic inflammation can be divided into 2 major entities, anterior uveitis with or without active epithelial keratitis or interstitial keratitis and viral retinopathy, which were described in both immunocompetent and immunocompromised patients.

Anterior uveitis is the most common form of intraocular inflammation accounting for more than 90% of uveitis, and herpetic anterior uveitis either due to herpes simplex or varicella zoster virus infection accounts for 5% to 10% of all uveitis cases and is the most common cause of anterior infectious uveitis.

Diagnosis of Herpetic Anterior Uveitis

Because not all clinicians have access to intraocular fluid analysis, awareness of the clinical symptoms of herpetic anterior uveitis is important for diagnosis and subsequent treatment. The diagnosis is relatively simple in the presence of concomitant skin lesions, active keratitis, and/or corneal anesthesia. However, in the absence of unclear evidence of current or past HSV infection, the diagnosis requires clinical suspicion and astute observations borne of such suspicion. Anterior uveitis secondary to HSV or VZV occurs in association with active or inactive corneal involvement, but anterior uveitis without associated corneal changes also occurs as an isolated entity.

Ocular involvement is virtually always unilateral, with patients suffering from blurry vision, photophobia, pain, and redness. On slit-lamp examination, we may find an active keratitis, corneal scaring, or normal cornea. The degree of intraocular inflammation can vary from mild to severe.

The iritis may be nongranulomatous but is more often granulomatous with moderate size mutton fat keratic precipitates (Figure 16-1), often in a triangular shape, located on the inferior part of the cornea, and, in the case of active keratitis, collects frequently under the area of the corneal lesion. Posterior synechiae, loss of the function of the sphincter muscles, and atrophy of the iris are responsible for a distorted pupil. The iris atrophy, which results from ischemic necrosis of the stroma, is characterized by a defect at the level of the iris pigment epithelium, has well-defined edges, and can be only seen with transillumination. It is in the specific search for such pathology via retroillumination that most ophthalmologists fail due to their lack of clinical suspicion for viral uveitis. Increased intraocular pressure is found in 90% of the patients, and trabeculitis is considered as the principal cause. Episcleritis and scleritis occur with anterior uveitis in less than 1% of patients.

Figure 16-1.Inferior granulomatous keratic precipitates. 

The diagnosis of herpetic anterior uveitis is usually based on the previously mentioned clinical features, but the gold standard is the isolation of the virus or viral antigens in intraocular liquid as aqueous humor, which is obtained after an anterior chamber tap or vitreous fluid in case of posterior involvement. Serological testing for anti-HSV is a useful epidemiological tool but is not diagnostically helpful in an individual patient.

Confirmation of intraocular viral infection with or without viral replication relies on molecular techniques such as polymerase chain reaction (PCR). The sensitivity of PCR to detect viral DNA can reach 80% to 96%, and it requires a small quantity of intraocular fluid. A less widely used method for the diagnosis of herpetic uveitis is the Goldmann-Witmer (GW) coefficient. This coefficient compares the ratio of anti-herpes antibody in serum and aqueous humor with the ratio of total immunoglobulin G in serum and aqueous humor, and is considered positive if the ratio is greater than 3. The GW coefficient is more useful in immunocompetent patients because of the high false-negative rate in immunocompromised hosts.

Treatment of Herpetic Uveitis

The pathogenesis of herpetic iridocyclitis is believed to involve active viral replication and the host immune responses.

Topical corticosteroids and antiviral agents are commonly used to treat ocular ­herpetic disease. Topical corticosteroids control the iridocyclitis and also acutely decrease intraocular pressure owing to their anti-inflammatory effects on trabecular meshwork. However, topical and oral antihypertensive agents may be necessary to control the pressure especially initially.

Corticosteroids should be slowly tapered once the inflammation is controlled to avoid “the rebound effect.” Topical antiviral agents promote resolution of herpetic epithelial keratitis, but their effect in deeper forms of ocular involvement has not been established. They should be used in concomitance with corticosteroid drops to prevent recurrent epithelial keratitis. The topical anti-herpetic agent of choice has become gancyclovir gel.

Concerning the use of oral acyclovir, the HEDS (herpetic eye disease control group) results suggest a benefit of oral acyclovir in the treatment of herpetic iridocyclitis in patients receiving topical corticosteroids and topical antiviral prophylaxis. Oral acyclovir at a dosage of 400 mg 5 times per day for several weeks is usually used. Intravenous acyclovir (10 mg/kg/d) may be considered in severe anterior uveitis and must be employed in all immunocompromised patients. Alternatively, one may use valacyclovir 1 g 3 times per day or famciclovir 500 mg 3 times daily. Oral acyclovir, 600 to 800 mg/day, given on a long-term basis, can diminish the recurrence of herpetic anterior uveitis.

I am not going to detail the viral retinopathies that are covered elsewhere in this work, but one must, for every anterior viral uveitis case, perform a dilated eye fundus to exclude any posterior involvement as an acute retinal necrosi