Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009

If used preoperatively, it should be given 1 - 1½ hours prior to surgery to get maximum effect.

Disadvantages: - Mannitol solution when exposed to low temperature will crystalize.

Adverse Reactions

Systemic hypertension, nausea, ↑ vomiting, marked diuresis, confusion, congestive cardiac failure, ↑ acidosis, ↑ dry mouth, ↑pulmonary edema, hyperglycemia.

Contraindicated in oliguria and anuria.

Prostaglandin Analogues

The drugs that come under this group include:

1)Latanoprost - 0.005% ( One drop once daily preferably in the evening).

2)Bimatoprost - 0.05% ( One drop once daily preferably in the evening).

3)Unoprostone -0.12% ( One drop twice daily).

4)Travoprost -- 0.03% ( One drop once daily preferably in the evening).

Latanoprost

It is prostaglandin PGF2 alpha analogue.

Latanoprost is a prodrug which is absorbed through cornea, where it is hydrolysed into the active form.

It decreases the IOP by increase in Uveoscleral outflow.

Effect of prostaglandin Uveoscleral outflow is caused by two probable mechanisms:

i)Relaxation of ciliary muscle

ii)Remodeling of extracellular connective tissue matrix around the ciliary muscle cells.

Latanoprost also has neuroprotective action by interfering with cyclo-oxygenase and nitric oxide synthetase activity thereby decreasing apoptosis of retinal ganglion cells.

Dosage and Administration

0.005% (50 mg / ml) once daily administration, which increases the patient compliance drastically.

Adverse Effects

Conjunctival hyperemia, superficial punctate keratitis, increased pigmentation of iris (due to increase in number of melanin granules in the iris), increased growth of eyelashes, increased pigmentation of eye lashes, foreign body sensation and grittiness are the main side effects encountered.

Bimatoprost

It is a prostanoid derivative acting through independent receptors. It reduces the IOP by increasing the Uveoscleral outflow.

It also upregulates the basic fibroblast growth factor (bfGF) which enhances the cell survival.

Calcium Channel Blockers

Calcium channel blockers such as diltiazem, nifedipine, nilvadipine and verapamil inhibit calcium influx in vascular smooth muscle decreasing the vascular tone and increasing the blood flow, these are particularly useful in patients with normotensive glaucoma.

NMDAAntagonists

It is directly acting non-IOP lowering neuroprotective agent.

N - Methyl D -Aspartate provides neuroprotection by blocking the glutamate, which drives cell death by facilitating calcium entry into the cell.

Glutamate is an important neurotransmitter in the retina. Under pathological conditions there is increase in the level of glutamate, which leads to cell death. Memantine—a non-competitive NMDA receptor antagonist derived from amantadine has got proven neuroprotective properties. Its non-competitive action blocks the toxic effects of glutamate without affecting the normal cell function.

Other drugs in research are—

Eliprodil: A non-competitive NMDA receptor antagonist. Riluzole: Presynaptic Glutamate release inhibitor.

L - Deprenyl: Monoamine Oxidase inhibitor, which gives protection to retinal ganglion cells. It also inhibits apoptosis.

Nitrous oxide inhibitors, Antioxidants, Free Radical scavengers are general Neuroprotective agents which prevent secondary retinal cell and ganglion cell damage.

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Viscoelastics

Viscoelastics refer to solutions that have dual properties—they act as viscous liquids as well as elastic solids or gels. In 1950's viscoelastic solutions were introduced as vitreous substitutes and in 1970's they were first used in anterior segment surgery. Balaz's introduced sodium hyaluronate as a replacement for aqueous and vitreous humor.

The ideal viscoelastic should be viscous enough to resist collapse of anterior chamber while at rest but liquid enough to be injected through small gauge cannula. The relevant characteristics of these agents are:

1.Viscoelasticity.

2.Viscosity.

3.Pseudoplasticity.

4.Surface tension.

Viscoelasticity is the ability of solution to return to its original shape after stress. Viscosity is resistance to flow determined by molecular weight. Pseudoplasticity is the ability to transform from a gel to liquid. Surface tension determines coatability, that is lower surface tension substances have better coatability.

The main functions of viscoelastics are:

1.Space maintenance.

2.Ease of injection and tissue manipulation.

3.Shock absorption.

4.Surface coating.

Space maintenance is dependent on solutions viscosity at rest. Higher molecular weight substances (HMW) have increased viscosity at rest and better space maintenance.

Tissue manipulation is dependent on pseudoplastic behaviour. HMW substances exhibit most pseudoplastic behaviour and better tissue manipulation.

Shock absorption is also dependent on molecular weight and pseudoplastic behaviour. Higher the elasticity, better the shock absorption.

Surface coating should prevent damage to endothelial cells during irrigation and other instrumentation. Surface coatability depends on surface tension. Lower surface tension has better coatability.

Depending on the above characteristics, viscoelastics can be classified as-

1.Cohesive.

2.Dispersive.

Cohesive viscoelastics adhere to each other are used for space maintenance, tissue manipulation, shock absorption and the easy to remove. They have high molecular weight. Dispersive viscoclastics have lower surface tension being less viscous are used for protecting corneal endothelium and coating instruments and intra-ocular lens.

Commonly used viscoelastics are:

1.Sodium hyaluronate.

2.Hydroxy propyl methyl cellulose.

3.Chondroitin sulphate.

Sodium hyaluronate is a biopolymer composed of two monosaccharide units found in aqueous and vitreous humor. It stimulates neutrophil function, cell proliferation, aggregation and migration facilitating wound healing. It is a mediator of ocular inflammation. It is available in higher and lower molecular weight concentrations. High molecular weight concentration has better space maintenance, and shock absorbing capabilities. Lower molecular weight substances are used in combination with other viscoelastics for their combined effect. It is produced by bacterial fermentation by genetic engineering.

Hydroxy propyl methyl cellulose 2% is a lower molecular weight substance derived from wood pulp. It is hydrophilic and can be irrigated from eye. It is viscoadherent with higher coatability and a dispersive viscoelastic.

Chondroitin sulphate is similar to hyaluronate and disappears from anterior chamber quicker than hyaluronate. It is derived from shark fin cartilage. It is mostly used in combination with hyaluronate (Sodium hyaluronate 4% and chondroitin sulphate 3%) so that, it has properties of both cohesive and dispersive agents.

Available viscoelastic agents areHyaluronate 1.4%

Hyaluronate ↑ 4% and Chondroitin 3 % HPMC ↑ 2 %.

The side effects are—

1.Increases IOP.

2.Occasionally increases intraocular inflammation leading to sterile endophthalmitis.

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Diabetes Mellitus

It is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. It is classifed into two types—

1.Type I diabetes: Results from autoimmune mediated destruction of beta cells of pancreas. This is characterized by severe insulin deficiency which needs to be replaced.

2.Type II diabetes: This is more common (90%) and is due to obesity, insulin resistance and relative insulin deficiency. Insulin secretion is usually

sufficient.

Gestational diabetes mellitus occur in 4% of pregnancies and resolves after delivery. Diagnosis of diabetes is made when—

1.Fasting blood glucose is > 126 mg/dl.

2.Random blood glucose >200 mg/dl.

3.Oral glucose tolerance test shows plasma glucose of 200 mg/dl or more

after 2 hours with 75 gm glucose load. The aims of treatment are—

1.Metabolic control.

2.Prevention of acute and long term complications.

Management of Diabetes Mellitus

1.Dietary modifications: It is more important in over weight persons.An intake of 10-20% of total calories should be proteins and less than 30% as fat.

2.Exercise: It improves insulin sensitivity, reduces fasting and post-prandial glucose.

3.Medications: It includes insulin and oral anti-hyperglycemic drugs.

Insulin Preparations

Type I diabetes requires life long insulin requirement. They differ by duration and peak activity.

1.Rapid acting insulin: These includes regular insulin, Lispro andAspart insulin. They can be administered by intravenous, intramuscular and subcutaneous route.

2.Intermediate acting insulin: Isophane and lente insulin are released slowly from sub cutaneous site.

3.Long acting insulin: It provides a steady basal level of insulin and is absorbed slowly from injection site.

Rapid acting insulin can be mixed with intermediate or long acting insulin. Premixed preparations are also available and this can be given subcutaneously in the abdominal wall thighs, arms. They are absorbed faster from abdomen due to the difference in blood supply.

Insulin dose is normally in the range of 0.5- 1units/kg/day. It is usually given as multiple daily insulin injections. 50% of insulin requirement is for basal insulin supply, which is by long or intermediate acting insulin and the remainder by rapidly acting insulin.

Insulin is administered before breakfast and before evening meal. 2/3 rd of daily dose is given in the morning.

Insulin secretagogues

1.Sulfonylureas: They lower blood glucose by augmenting insulin secretion. They should be taken 1/2- 1 hour before food. Dose should be started with lower concentration and gradually increased over several days. Hypoglycemia and weight gain are the common side effects.

2.Repaglinide: This stimulates insulin secretion and has a very short duration of action. They should be taken 1/2 hour before meals.

3.Nateglinide: It acts directly on pancreatic beta cells and stimulates insulin secretion. It should be taken 10 minutes before food. It controls postprandial hyperglycemia.