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RETILONE MEDICAL NOTE

Q. Why age related visual impairment diseases are important ?

A. Age related visual diseases are important because :

• Age-related visual impairment is second only to arthritis/rheumatism as a cause of disability.

• Vision loss ranks third after arthritis and heart disease as the reason for impaired daily functioning in people over the age of 70.

Q. What are the current vision challenges ?

A. Current vision challenges are :

• Although more than 1.6 million Americans over age 60 currently have Age-related Macular

• Degeneration, approximately 30 million Americans over age 40 are at risk of developing it.

• Diabetic Retinopathy affects more than 5.3 million Americans age 18 or older, the leading cause of blindness in the industrialized world in people between the ages of 25 and 74

Q. How does vision impairment affects quality of life ?

A. Vision impairment affects quality of life in the following ways:

• Vision impairment is associated with a diminished quality of life.

• Older adults with impaired vision are less able to perform routine activities of daily living, are less mobile, are more isolated, suffer higher rates of depression,.

• Impaired vision is a signifi cant independent risk factor for falls and fractures in older people.

• The ability to travel independently, often linked with issues of quality life, becomes challenging and daunting in the presence of vision loss

• Visually impaired older adults fi nd it diffi cult, if not impossible, to read for pleasure, watch television, movies and sports for recreation with friends and family, barring them from the most common forms of social engagement, which can further add to a sense of isolation and depression.

Q. Which are the retinal diseases which are commonly seen in elderly people ?

A. The retinal diseases which are commonly seen in elderly people are:

• Diabetic Retinopathy

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• Diabetic Macular Edema

• Age related macular degeneration

• Central retinal vein occlusion

• Branch Retinal vein occlusion

• Cystoid macular edema

Q. Explain in brief about retina ?

A. The details about retina are as follows :

• Third and inner coat of the eye ball

• Lines the posterior three quarters of the eyeball

• Circular disc of approximately 42 mm diameter

• Retina is about 200-250 micrometers thick

Q. Explain in brief about macula ?

A. The details about macula are as follows :

• The macula is the posterior aspect of the retina

• Has highest concentration of photoreceptors which facilitate central vision and permit high resolution visual acuity

• The macula is an area up to 5.5 mm in diameter with the fovea at its centre

• The retinal pigment epithelium (RPE) is a single layer of hexagonally shaped cells. They reach out to the photoreceptor layer of the retina

• Functions of RPE includes maintainance of the photoreceptors, absorption of stray light, formation of the outer blood retinal barrier, phagocytosis and regeneration of visual pigment

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• Bruch’s membrane separates the RPE from vascular choroid,

• Function of Bruch’s membrane is to provide support to the retina

• Choroid capillaries are a layer of fi ne blood vessels that nourishes the retina and provides O2

Q. How does vision occurs ?

A. The vision occurs as a result of the following processes :

Also, trans-retinal -> recycled to cis-retinal in RPE.

This entire process requires oxygen and nutrition supplied by the fi ne blood vessels of the choriocapillaries

Q. Explain in brief the blood supply to the retina ?

A. The blood supply to the retina is as follows :

• Derives its blood supply from the ophthalmic artery.

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• Outer retina is supplied from the choriocapillaries

• Inner retina is supplied from central retinal artery

• Central retinal artery is a branch of the ophthalmic artery that begins about 4 mm posterior to the optic nerve head.

• Branch enters the optic nerve and divides into 2 more branches in the optic nerve

• The vessels further divide to supply each quadrant of the eye with an artery and a vein

Q. What is diabetes ?

A. Diabetes mellitus is a condition in which the body does not make insulin or the body cannot use insulin properly.Insulin is the hormone responsible for the converting blood sugar into useful energy

Q. List the different types of diabetes

A. The different types of diabetes are :

1) Type 1 diabetes or insulin dependent diabetes

2) Type 11 diabetes or non insulin dependent diabetes

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Type 1 or insulin dependent diabetes

• Insulin Dependent Diabetes Mellitus

• Used to be called juvenile onset diabetes

• Most commonly begins during childhood

• Cells that produce insulin in the pancreas have been destroyed by the immune system

• Accounts for about 15% of people with diabetes

• Need daily injections of insulin to survive

TYPE 11 or non insulin dependent diabetes

• Pancreas doesn’t produce enough insulin or cells ignore it (insulin resistance)

• Most people with diabetes have type 2 (85%)

• Generally occurs in those over 40 years old

• Associated with obesity and runs in families to some extent

• Build-up of glucose more slow – often unnoticed

• 30%-50% will require insulin injections

• Lifestyle issues prominent

Q. What is the prevalence of diabetes Globally and in India ?

A. The prevalence of diabetes globally and in India is as follows :

• Estimated to have affected 171 million people worldwide in 2006

• Projected to affect 366 million by 2030

• Considerable concern because of severe long term complications

• Four leading cause of death in industrialized nationsAs a result of the explosion of diabetes in India, currently 40.9 million individuals are estimated to be affected and

• Diabetic retinopathy may pose a therapeutic challenge

Q. Are there any prevalence study conducted in India for diabetic retinopathy ?

A. The prevalence study conducted in India for diabetic retinopathy is :

CURES: The Chennai Urban Rural Epidemiology study

No. of patients: 1736 type 2 diabetes subjects1382 known diabetes 354 newly detected diabetes

All subjects underwent four-fi eld stereo retinal colour photography

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Results: Overall Prevalence of Diabetic Retinopathy 17.6%

Ref: Diabet. Med. 2008; 25: 536-542

Q. Explains the pathogenesis of diabetic retinopathy ?

A. The pathogenesis of diabetes retinopathy is as follows :

Diabetic Retinopathy: Pathogenesis

Mechanisms that have been proposed are:

1. Hyperglycemia may alter the expression of one or more genes, leading to increased (or decreased) amounts of certain gene products that can alter cellular functions

2. Glycosylated proteins can undergo a series of reactions, leading to considerable alteration of proteins

3. Chronic hyperglycemia may produce oxidative stress in cells, leading to the formation of an excess of “toxic end products of oxidation” including peroxides, superoxides, nitric oxide, and oxygen free radicals

Q. List the signs of diabetic retinopathy ?

A. The signs of diabetic retinopathy are :

• Aneurysm :

Microaneurysms are areas of balloon like swelling of the tiny blood vessels in the Retina caused by the weakening of their structure

• Dot-blot haemorrhages

• Cotton wool spots

• Neovascularization

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Q. List the symptoms of Diabetic Retinopathy ?

Ans: The symptoms are Diabetic Retinopathy are :

• Blurred, Hazy or Double vision

• Visual fl uctuations

• Diffi culty with fi ne details .

• Some loss of fi eld vision.

• Diffi culty seeing at night or in low light. Sensitivity to light or glare.

• Trouble Focusing images

Q. How is diabetic retinopathy classifi ed ?

A. Diabetic retinopathy has four stages:

• Mild Nonproliferative Retinopathy. At this earliest stage, microaneurysms occur. They are small areas of balloon-like swelling in the retina’s tiny blood vessels.

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• Moderate Nonproliferative Retinopathy. As the disease progresses, some blood vessels that nourish the retina are blocked.

• Severe Nonproliferative Retinopathy. Many more blood vessels are blocked, depriving several areas of the retina with their blood supply. These areas of the retina send signals to the body to grow new blood vessels for nourishment.

• Proliferative Retinopathy. At this advanced stage, the signals sent by the retina for nourishment trigger the growth of new blood vessels. This condition is called proliferative retinopathy. These new blood vessels are abnormal and fragile.

Q. How does diabetic retinopathy causes vision loss ?

A. Diabetic retinopathy causes vision loss as follows :

• Blood vessels damaged from diabetic retinopathy can cause vision loss in two ways:

• Fragile, abnormal blood vessels can develop and leak blood into the center of the eye, blurring vision. This is proliferative retinopathy and is the fourth and most advanced stage of the disease.

• Fluid can leak into the center of the macula, the part of the eye where sharp, straight-ahead vision occurs. The fl uid makes the macula swell, blurring vision. This condition is called macular edema. It can occur at any stage of diabetic retinopathy, although it is more likely to occur as the disease progresses. About half of the people with proliferative retinopathy also have macular edema

Q. List the various diagnostic techniques used to diagnose Diabetic Retinopathy

A. The various diagnostic techniques to diagnose diabetic retinopathy are as follows

• History

• Visual Acuity

• Eye Movement

• Refraction

• Intraocular Pressure measurement

• Visual Field evaluation

• Dilated Retinal examination

• Stereoscopic fundus photography thro dilated pupils → grading by ETDRS

• Indirect ophthalmoscopy: Examines the extent of damage to the retina due to ischemia, thickness of the retina

• Fundus angiography [fl uorescein Angiography] : Check the leakage of blood/fl uid from newly formed blood vessels and locates the point of leakage

• Optical coherence Tomography (OCT) : Imaging technique that produces high resolution cross-sectional images of the macula

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• OCT is less invasive

• Allows for earlier and more sensitive diagnosis

• Takes less time

• Demonstrates greater anatomical details

Q. How is diabetic retinopathy managed ?

A. Diabetic retinopathy is managed by following ways :

• Glycaemic control

• Blood pressure control

• Smoking control

• Anti-oxidants

• Anti-VEGF’s

• Steroids

• Laser photocoagulation

• Vitrectomy

Q. List the various laser treatment strategies

A. The various laser treatment strategies are as follows :

Focal treatment is used to treat

macular edema due to focal

leakage. The laser is applied to

specifi c diseased areas to seal

up tiny bulges near the fovea

Grid treatment is used to treat

macular edema due to diffuse

leakage. The laser is applied in

a series of circles around the

fovea to reduce swollen areas.

Panretinal treatment may be

used to treat pre-proliferative

and proliferative retinopathy.

The laser is applied around

the fovea to reduce new blood

vessel growth.

Q. Explain Diabetic macular edema ?

A. Diabetic macular edema can be explained is as follows :

Swelling of the retina in diabetes mellitus due to leaking of fl uid from blood vessels within the macula.

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• Can occur at any stage of diabetic retinopathy

• Is caused by the leakage of microaneurysms

• Is the main cause of visual impairment in patients with Diabetic retinopathy

• Caused by the accumulation of intraretinal fl uid in the retinal layers.

• Hyperpermeability of the retinal vasculature.

• Can be present with any level of diabetic retinopathy (DR).

Q. What is the prevalence of diabetic macular edema ?

A. The prevalence of diabetic maculae edema is as follows:

• Affects up to 10% of all patients with diabetes

• Up to 75,000 new cases occur every year

• Up to 30% of patients with DME will experience moderate visual loss

Q. List the symptoms of diabetic macular edema

A. The symptoms of diabetes macular edema are as follows:

• Blurred vision

• Double vision

• Floaters (small black dots or lines made up of cellular debris seen "fl oating" across the front of the eye) These fl oaters may temporarily interfere with vision.

Q. What are the different types of diabetes macular edema ?

A. The different types of diabetes macular edema :

• Focal DME is caused by tiny abnormalities in blood vessels, known as microaneurysms. These leaking microaneurysms can lead to vision loss.

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• Diffuse DME is caused by widening (dilation) of retinal capillaries (extremely thin, narrow blood vessels) throughout the back of the eye.

Q. What is CSME ?

A. Clinical signifi cant macular edema is defi ned as :

• Retinal thickening at or within 500 μ from the center of the macula

• Hard exudates at or within 500 μ from center of the macula with thickening of adjacent retina

Q. What are treatment options for diabetic macular edema ?

A ns : Diabetic macular edema is treated by the following ways :

• Laser Treatment

• Steroid Implants and devices to the posterior segment

• Intravitreal injection of triamcinolone acetonide-for diffuse diabetic macular edema

• Fluocinolone acetonide intravitreal implants

Q. How is ARMD classifi ed ?

A. ARMD is classifi ed as follows:

Two main types

Dry (non-exudative, atrophic) type

Wet (exudative, neovascular) type

Dry ARMD

• Most common

• Atrophic or nonexudative

• Drusen

• Geographic atrophy

Symptoms

• Blurry or fuzzy vision

• Decreased contrast sensitivity

• Decreased ability to distinguish colors

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Wet ARMD

• Exudative or neovascular

• Abnormal vessels growing beneath the retina

• Blood vessels bleed and leak fl uid

• Results in disruption and eventual death of photoreceptors

• Disciform scar

Symptoms

• Distortion

• Spot in central vision

• Sudden decline in central vision

Q. How does Wet ARMD occurs ?

A. Wet ARMD occurs as follows :

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Q. List the diagnostic tests used to diagnose ARMD ?

A. The diagnostic tests used to diagnose ARMD :

• Visual acuity

• Amsler grid

• Dilated fundus exam

• Fluorescein angiography (FA)

• Ocular coherence tomography (OCT)

Amsler Grid

• Self-monitoring

• Tested in offi ce

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Fluorescein Angiography

Q. List the treatment options for ARMD ?

A. The various treatment options for ARMD are :

• Laser photocoagulation

• Laser aimed at choroidal neovascular membrane

• Used for juxtafoveal and extrafoveal lesions

• 3 year recurrence 50%

• Surgical

• Removal CNVM not shown to be benefi cial

• Macular translocation- numerous complications and not in vogue

Photodynamic Therapy (PDT)

• Utilizes a photoactive drug verteporfi n

• Drug is activated by laser

• Drug administered over 10 minutes

• Activation of drug results in oxygen free radicals

• Leads to vascular thrombosis in the treated area with abnormal blood vessels

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Q. What is VEGF ? Explain in BRIEF the various ANTI-VEFF’S available ?

A. In ARMD, the retinal pigment epithelial cells (RPE) begin to wither from lack of nutrition (ischemic), the VEGF-A goes into action to form new vessels.This process is called as “NEOVASCULARIZATION”.NEW BLOOD VESSELS originate from choriod and it is called choroid neovascularization ( CNV)

VEGF-A

• Involved in progression of retinal vascular diseases such as AMD

• Several types (isoforms) • Involved in angiogenesis

• Causes abnormal blood vessel growth

• Causes blood vessels to leak

Anti-VEGF agents

Pegaptanib (Macugen):

• Aptamer – synthesized RNA

• Binds VEGF-A 165

• Intraocular injection every 6 weeks

• Marginal results

– 6% of treated eyes had improvement in vision

– 70% maintained vision (55% in sham group)

– 12% fewer patients with severe vision

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Ranibizumab (Lucentis)

• Recombinant humanized monoclonal antibody

• Binds all isoforms of VEGF-A

• Intraocular injection every month

• Promising results

– 30-40% of patients improved vision

– 94.6% of patients maintained vision (62% sham)

– Approved June 2006

– Bevacizumab (Avastin)

• Off-label for intravitreal injection

– Approved to treat colon cancer

– Given intravenously

• Lucentis – cleaved portion of Avastin

– Larger molecule thought too big to penetrate the retina effectively

– Similar results to Lucentis in many case-series

– Much less expensive

Q. What are the side effects of ANTI-VEGF’S ?

A. The side effects of Anti-vegf’s are :

• Side effects of Anti-VEGF’s agents include thrombosis, hypertension, edema and proteinuria

• Therapeutic doses of anti-VEGF, for AMD are smaller and administered more infrequently than cancer

• Many opthalmologists have yet to report an increased incidence of cardiovascular events

Q. What is retinal vein occlusion? What are its different types ?

A. Retinal vein occlusion is defi ned as :

Retinal vein occlusion occurs when the circulation of a retinal vein becomes obstructed by an adjacent blood vessel causing hemorrhages in the retina. Swelling and ischemia (lack of oxygen) of the retina as well as glaucoma are fairly common complications.

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The different types of Retinal vein occlusion is as follows :

• Branch Retinal Vein Occlusion” or BRVO denotes obstruction of this blood fl ow in small branches of retina

• Central Retinal Vein Occlusion” or CRVO denotes obstruction of blood fl ow in the main and large vein of the retina.

Q. List the symptoms of Retinal vein occlusion ?

A. The symptoms of Retinal vein occlusion are :

• Blurred or missing area of vision (if a branch vein is involved)

• Severe loss of central vision (if a central vein is involved)

Q. What is Chalazion ?

A. Chalazion is explained as follows :

• A chalazion (stye) is a small lump in the eyelid caused by obstruction of an oil producing meibomian gland

• A chalazion is a non-infectious, granulomatous infl ammation of the meibomian glands.

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• Lipid breakdown products, possibly from bacterial enzymes (as free fatty acids) or from retained sebaceous secretions, leak into the surrounding tissue and incite a infl ammatory response.

• The resulting mass of granulation tissue and chronic infl ammation (with lymphocytes and lipid-laden macrophages)

Q. List the causative factors for Chalazion ?

A. The causative factors for Chalazion are :

• Blockage of a gland orifi ce or due to an internal hordeolum.

• Associated with seborrhea, chronic blepharitis, and acne rosacea.

• Poor lid hygiene is occasionally associated with chalazia

• Stress is often apparently associated with chalazia

Q. List the symptoms of Chalazion ?

A. The symptoms of Chalazion are :

Signs and Symptoms

• Raised, swollen bump on the upper or lower eye lid

• Often red

• May be tender and sore

Q. What are the treatment modalities for chalazion ?

A. The treatment modalities for Chalazion include :

• Conservative treatment with lid massage, moist heat, and topical mild steroid drops

• Use of antibiotics like doxycycline 100mg od for 10 days

• Intravitreal traimcinolone

• Surgery

Q. Explain Cystoid macular edema ?

A. Painless condition in which swelling or thickening occurs of the central retina (macula)

Associated with various ocular conditions, such as cataract surgery, age-related macular degeneration (ARMD), uveitis, eye injury, diabetes, retinal vein occlusion, or drug toxicity

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• Blurred or decreased central vision (the disorder does not affect peripheral or side-vision)

• Painless retinal infl ammation or swelling (usually after cataract surgery)

Q. Explain vernal keratoconjunctivitis ?

A. • Vernal keratoconjunctivitis (VKC) is a recurrent ocular infl ammatory disease that has a seasonal incidence.

• It tends to occur more in dry, warm climates.

• Affects children and young adults.

• Primarily found in men between the ages of 3 and 20 years.

• Characterized by hard, elevated, cobblestone like bumps on the upper eyelid.

• Swellings and thickening of the conjunctiva..

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Q. Explain in brief about triamcinolone acetonide ?

A. • Corticosteroids have been used to treat infl ammatory conditions of the eye since the 1950s and been injected intraocularly since 1974

• Triamcinolone acetonide has been effectively used in ocular therapeutics for over 50 years

• In 1970 Machemer et al were the fi rst to use IVTA in an animal model with retinal detachment

• The fi rst intentional intraocular injections of triamcinolone in humans was administered in 1993

Ref: Survey of ophthalmology Vol.52; No. 5; Sept-Oct 2007; 303-522Current Diabetes Review; 2006: 2, 99-112

Q. List the key features of Intravitreal triamcinolone acetonide ( IVTA)

A. The key features of intravitreal triamcinolone acetonide are :

• Corticosteroid with practically no water solubility which prolongs its presence in the vitreous nearly 5 times as compared to hydrocortisone

• Insolubility of triamcinolone in water, allows the drug to remain in the vitreous cavity for a longer duration simulating a system of sustained delivery

• Crystalline nature together with its sequestration in the vitreous ensures effective concentration close to the choroidal neovascular membrane

Current Diabetes Review; 2006; 2, 99-112

Q. Explain the pharmacokinetics of intravitreal triamcinolone

A. The pharmacokinetics of intravitreal triamcinolone is as follows :

Peak aqueous humor concentration 2150-7202 ng/ml

Half life 76 – 635 hours

AUC 231-1,911 ng.h/ml

Mean Elimination half-life 18.7 days

Ref: Trisence Package insert; 2008

• Rate of IVTF disappearance depended on the presence or absence of the lens or vitreous

• Normal eyes: 41 days

• Eyes with post-vitrectomy: 17 days

• Eyes with post lansectomy vitrectomy: 6.5 days

Surv of ophthalmology Vol. 52; No. 5 Sept 2007; 503-522

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Q What is the mechanism of action of IVTA?

A. The mechanism of action of IVTA is as follows :

• Act locally reducing infl ammatory mediators

• Down regulate the production of VEGF

• Reduce the breakdown of blood retinal barrier

• Improving oxygenation to the ischemic areas

• Intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 Major histocompatibility complex (MHC)-I and II Key indicators of vascular endothelial cell activation

• ICAM 1, MHCI and MHC-II down regulated

• Vasoconstrictive effects

• Infl ammatory processes (edema, fi brin deposition, capillary dilatation, migration of leukocytes and phagocytosis) are inhibited

Ref: Surv. of ophthalmology: 52:502-522; 2007

Q. Are there any documented study stating that IVTA without preservative is better that IVTA with preservative

A The study documented that IVTA without preservative is better than IVTA with preservative is as follows :

AimTo evaluate the effects of intravitreal injection of preservative free TA and TA containing preservative.

Patients

471 eyes received 646 IVTA 4 mg/0.1 ml

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577 → PFTA

69 → TA with preservative in non-randomized eyes

Q. What are the product details of RETILONE ?

A. The product details of RETILONE are as follows :

• Each ml of the sterile aqueous suspension provides 40 mg of triamcinolone acetonide

• Contains povidone IP,disodium hydrogen phosphate dihydrate ,sodium dihydrogen dihydrate,sodium chloride, hydrochloric acid, water for injection

• PH : 6.0, osmolality : 308

• Each vial should only be used for the treatment of a single eye

Q. What is the particle size of RETILONE ?

A. The particle size of Retilone is as follows :

• Plays an important role in the pharmacokinetics of triamcinolone acetonide

• Ideal particle size: 1-5 mm range

• Retilone particle size: 5mm

Q. List the indications, the dosage and administration of RETILONE ?

A. The indications and the dosage and administration of RETILONE are as follows :

• Diabetic Retinopathy

• Exudative ARMD

• Diffuse Diabetic Macular Edema

• Macular edema secondary to CRVO and BRVO

• Chronic cystoid macular Edema

• Retinal detachment

• Iritis, iridocyclitis, chloroiditis, uveatis

• Visualization of vitrous during vitrectomy

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DOSAGE AND ADMINISTRATION :

• For Ophthalmic Diseases

• 4 mg (100 microliters of 40 mg/ml suspension) with subsequent dosage as needed over the course of treatment

• For visualization during vitrectomy

• 1 – 4 mg (25 to 100 microliters of 40 mg/ml suspension) administered intravireally.

Q. Explain in brief the effi cacy study of IVTA in proliferative diabetic retinopathy ?

A. • Prospective, double masked, placebo controlled, randomized clinical trial

• No. of eyes: 69 of 43 patients 34 eyes: IVTF 4 mg 35 eyes: placebo

• Results

Reduction in macular edema

Short term, IVTF is an effective andrelatively safe treatment for

eyes with proliferative diabetic retinopathy.

Study 1 : To evaluate the effect of IVTF in eyes with DME as primary therapy

No. of patients : 12 patients (age 47-70 years)Central macular thickness: 448.6 mm

Treatment : Single injection of IVTF 0.1 ml (4 mg)

Follow up : 6 months

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Q. Explain in brief the effi cacy of IVTA as a primary therapy in DME ?

Conclusion: Promising therapeutic modality in the management of DME

Q. What is the role of IVTA in CSMO ?

Study 2 : Effi cacy and safety in Chinese patients with diabetes clinically signifi cant macular edema (CSMO)

No. of patients : 18 eyes of 17 patients with CSMO for 12.9 months given IVTF 4 mg

Parameters : BCVA, CMT (Central Macular Thickness)Assessed

• 78% achieved a maximum improvement of 2 or more lines

• 50% maintained the visual impairment

• Maximum benefi cial effect achieved at 2-3 months

• 28% showed rise in IOP

Conclusion

• IVTF appeared safe and effective in Chinese patients with CSMO

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Q. What is the role of IVTA in refractory DME ?

Study 3 : Use of IVTF in DME unresponsive to previous laser photocoagulation

No. of patients : 30 eyes of 22 patients

Treatment : IVTF injection 4 mg in 0.1 ml

Follow up : 1 day, 1 week, 1 month, 3 months and 6 months

Parameters : Visual acuity, CMT reduction

Q. What is the role of IVTA in refractory diffuse DME ?

Study 4 : Effi cacy and safety of 1 injection of IVTA (4 mg in 0.1 ml) for refractory diffuse macular edema.

Patients : 17 with bilateral DME unresponsive to laser therapy (2 sessions) One eye was injected and the other served as control

Main outcome : Reduction in CMTmeasure

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Conclusion: IVTA appears to be dramatically effective in decreasing retinal thickness in diffuse CMO and seems to have real potential to improve VA.

• Stabilises the blood-retinal barrier

• Down regulates the production of VEGF

• New alternative to laser therapy.

• Rapid resolution of macular edema and improvement in visual acuity.

• Promising treatment for patients with DME refractory to laser Rx.

Current Diabetes Reviews, 2206;2,99-112.Eur. J. Ophthalmol 2004; 14:543-9.

Act. Ophthalmol Scand.;2006;84:624-630.

Q. Explain in brief the effi cacy study of IVTA in CRVO ?

Aim: Effi cacy of IVTA in the management of CRVO

Patients: 20 for treatment group (3-4 month history of CRVO and persistent macular edema) 20 patients in observation group

Treatment: Single injection of IVTA (40 mg/ml)

Follow-up: 10-12 months

Conclusion

• IVTA is a safe treatment for macular edema in CRVO

• Rapid improvement in VA resolution of macular edema

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Q. Explain in brief the role of IVTA in exudative ARMD ?

Aim: Evaluate the safety and effi cacy of IVTA after 18 months of follow up in patients with exudative ARMD

Patients: 30 eyes of 28 patients

Treatment: IVTA injection (4 mg)

Primary measure: Proportion of eyes with loss of six or more lines on a Bailey-Lovie chart Incidence of side effects

• 3 patients developed cataract

• 2 patients developed glaucoma

Q. Is there any synergistic effects seen when IVTA and ANTIVEGF’S are used together

Aim: Effi cacy of intravitreal injection of bevacizumab (1.25 mg/0.05 ml) and triamcinolone (2 mg/0.05 ml)

Patients: 30 consecutive eyes of 27 patients

Follow up: 1 and 8 weeks

Parameters: Foveal thickness, sub foveal fl uid volume reduction

Conclusion: IVTA is an important adjunct with anti-VEGF in exudative ARMD

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Q. Is there any study documenting the use of IVTA and PDT together ?

Aim: Effects of IVTA as an adjunctive treatment to PDT for CNV in ARMD Retrospectively evaluated the records of 14 patients who had IVTA within 6 weeks of their fi rst PDF and had a follow up of >1 year

Results: 7% gained > 30 letters, 50% maintained stable vision, 14% lost 15-29 letters, 29% lost >30 letters

Conclusion: IVTA + PDT is effective and safe in patients with CNV

Q. List the highlights of IVTA in Exudative ARMD

• Crystalline nature of the drug together with its sequestration in the vitreous, ensures an effective conc. Close to choroidal neovascular membrane

• Synergistic effect of IVTA with anti-VEGF’s

• IVTA with PDT effective and safe in exudative AMD

Q. What are the allied indications where IVTA is being explored ?

• CME is a common complication after ECCE in 10-30% of patients

• Patients

– 6 eyes of 6 patients with chronic pseudophakic CME aged 58-74 years

– All eyes had persistent CME despite having medical treatment for at last 3 months

– IVTA 4 mg (0.1 ml) was given

IVTA is a promising therapeutic method for chronic pseudophakic CME resistant to medical treatment

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51 eyes of 37 patients who underwent transtenon’s retrobulbar infusion of triamcinolone for uveitic infl ammation (0.5 ml of 40 mg/ml → total dose 20 mg)

Trans-Tenon’s retrobulbar tramcinolone infusion is safe and effective treatment for posterior uveitic infl ammation

No. of patients: 38 eyes of 19 patients with recalcitrant VAC

Supratarsal injection was given of either 2 mg of dexamethasone sodium phosphate or 20 mg of IVTA

Economical, effective and safe modality of treatment of managing eyes with recalcitrant VKC

Both agents were equally quick acting and effective in providing symptomatic relief

Provides initial symptom relief

Mean time of resolution (in Mean time of resolution days)

Outcome measure Dexamethasone 17 eyes Triamcinolone 21 eyes

Symptomatic relief 2.2 2.5

Cobble stone papillae 11 – 8 12 – 0

Limbal edema 16 14

Shield ulcer 16 14

SPK 18 21

• Vitreous loss is a common complication of cataract surgery, occurring in 1%-7% of cases

• Vitreous is present in the anterior chamber and the surgeon is unable to visualize it at the operating microscope

• IVTA suspension injected directly into the anterior chamber tended to swirl freely excepts in areas where vitreous gel was present

• IVTA particles entrapped in the vitreous gel

• IVTA-assisted anterior vitrectomy allowed surgeons to be thorough and effi cient because they were able to see exactly where the vitreous was and verify they had removed all of it in the anterior chamber

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Objective

• To study the effi cacy of subcutaneous steroid injection of chalazion

Design

• Prospective, consecutive case series

Patients

• 48 given triamcinolone 10 mg/ml subcutaneously

Q. What are the side effects of IVT A ?

A. The side effects of IVTA are :

• Elevated IOP and cataract progression: 20-60%

• Endophthalmitis: 2%

• Fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain

Q. List the contraindications for RETILONE ?

A. The contraindications for RETILONE :

• Patients with systemic fungal infections

• Hypersensitive to corticosteroids or any component of this product

Q. List the drug interactions for IVTA ?

A. The drug interactions for IVTA are as follows :

• Potassium depleting Agents: (e.g. diuretics, Amphotericin B): hypokalemia, cardiac enlargement and congestive heart failure

• Anticholinesterase agents: concomitant use may produce severe weakness in patients with myasthenis gravis

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• Anticoagulatants: coagulation indices to be monitored

• Anti-diabetic agents: Steroids increase blood glucose, dosage adjustments required

• Anti-tubercular drugs: serum concentration of isoniazide decreased

• CYPA3A4 inducers (e.g. barbiturates, phenytoin, carbamazepine and riampin) enhances metabolism of steroid

• CYP3A4 inhibitors (e.g.: ketoconazole, macrolides) Decrease metabolism of steroids

• Cholestyramine: Increase clearance of steroids

• Cyclosporine: Increased activity of both have been reported

• Digitalis: Increased risk of arrhythmias

• Estrogens, oral contraceptives: Decrease hepatic metabolism of steroids

• NSAIDs including aspirin and salicylates: Risk of gastrointestinal side effect

• Skin tests: suppress skin reactions

• Vaccines: should not be administered

Q. What are the recommendations of IVTA for special population ?

A The recommendation s of IVTA for special population are as follows :

• Pregnancy: Category D: Risk to Benefi t Ratio

• Nursing mothers: Risk to benefi t Ratio

• Pediatric use: Recommended > 6 years of age

• Geriatric use: same as that in adults

Q. How is Retilone supplied ?

A. Retilone is supplied is as follows :

• Retilone (triamcinolone acetonide injectable suspension) is supplied as 1 ml of a 40 mg/ml sterile triamcinolone acetonide suspension in a fl int type 1 single use moulded glass vial with a gray bromobutyl rubber closure

Q. What are recommendations for administering Retilone ?

• Strict aseptic technique is mandatory

• Vial should be vigorously shaken for losers before use to ensure a uniform suspension

• Prior to withdrawal, the suspension should be inspected for clumping or granular appearance

• After withdrawal, triamcinolone should be injected without delay to prevent setting in the syringe

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• Use fresh sterile hypodermis 27 gauge needle

• Injection procedure should be carried out under controlled aseptic conditions

• Use of sterile gloves, a sterile drape and a sterile eyelid speculum

• Patients should be monitored for IOP elevation and endophthalmitis. Tonometry: 30 mins following the injection

Bimicroscopy: 2 and 7 days

Q. What are the storage conditions for RETILONE ?

A. The storage conditions for RETILONE are :

• Stored between 4o and 25o C

• Protect from light and freezing

• Protect from light by storing in carton

Q. List the highlights of RETILONE

A. The highlights of RETILONE are as follows ;

• Crystalline nature of the drug together with its sequestration in the vitreous, ensures an effective concentration in the vitreous cavity

• Stabilises the blood-retinal barrier

• Down regulates the production of VEGF

• Synergistic effect of IVTA with anti-VEGF’s

• IVTA with PDT effective and safe in exudative AMD

• New alternative to laser therapy.

• Rapid resolution of macular edema and improvement in visual acuity.

• Promising treatment for patients with DME refractory to laser Rx.

• Safe and effective in treating uveitis

• Quick symptom relief in recalcitrant VKC