IOP Spike Control after Intravitreal Anti-VEGF

IOP Spike Control after Intravitreal Anti-VEGFIn ophthalmology some(prenominal) ophthalmic procedures atomic payoff 18 there in which there is a capitulum of intraocular pressure after the procedures. Cataract surgery, argon laser trabulectomy ( elevated railroad), yag laser capsulotomy, yag laser iridotomy, trabulectomy, pars plana vitrectomy ar few to be named. The new anti VEGF therapy is an addition to the prior list. umteen IOP lowering drugs aro social function been customd in different procedures to stop these spikes. For ALT 1% apraclonidine, an of import agonist has been found to be the most dropful against the IOP spikes, but 0.5% has excessively been found to be equally feative. Brimonidine an alpha 2 adrenergic agonist has similarly been shown to be legal and safe choice.For cataract surgery different drugs suck up been apply treat the postoperative increase in IOP. These include carbonic anhydrase inhibitors, prostaglandin analogs like latanoprost, alpha agonists like apraclonidine and brimonidine, beta-blockers and miotics (intracameral carbachol and acetylcholine).Similarly intravitreal shaft of triamcinolone has been complicated with a rise of IOP and have been controlled lay outively by beta blockers, but some may need aggressive treatment. antithetic researchers have worked on the control of acute spikes after the intravitreal shooting of anti-VEGF, wake varied result. Some have advocated the use of IOP lowering medicine slice other negating the need all together.Lim Young et al showed that the prophylactic use of firm dorsolamide/timolol combination gist drops before the intravitreal anti-VEGF injection was a safe method of preventing IOP spikes occurring immediately after the intravitreal injection of anti-VEGF. He showed that the tight IOP at 5 minutes and 30 minutes postoperative was 14.12 4.18 mm Hg and 10.87 1.58 mm Hg in group 1 utilise IOP lowering medication while it was 28.21 3.16 mm Hg and 17.48 2.34 mm Hg in control group 2, respectively.9 He showed that there was a material lowering of hateful IOP at each reading at 5 minutes of interval.Frenkel et al showed the use of IOP-lowering medication prior to injection of pegaptanib, ranibizumab, or bevacizumab had little inwardness on the IOP spike. The failure of lowering the IOP spike was concerned to be repayable to the inability of these medications to counteract the volume-related mechanism of the IOP spikes after anti-VEGF injections. However, it was give tongue to that there might be benefit to lower the IOP before intravitreal injection. In their study 2 cases of sudden loss of vision were reported due to the high IOP spike which prompted them to do anterior chamber paracentesis.8 It was as well verbalize that the prophylactic use of medication in tolerants with advanced glaucoma receiving pegaptanib intravitreal injection or patients receiving 0.1 ml of bevacizumab could be con rampred be app arent movement their study showed that it lowered IOP at the 3- to 10-minute interval in these patients.In another study done in 2013 the IOP lowering effect of Dorzolamide/Timolol and Brinzolamide/Timolol were comp ard with a control group. They measured the IOP after any 5 minutes for the first half time of twenty-four hours and the next twenty-four hour period and week after that. For all the 3 groups, the changes relative to the baseline at 5 and 30 minutes after intravitreal injection was found to be signifi quartert. Also when the groups were broken down as to whether receiving bevacizumab or ranibizumab, again the mean simplification of IOP comp bed to the control group was found significant.El Chehab et al have overly found that the prophylactic use of fixed combination of timolol with brimonidine or dorzolamide and of 1% apraclonidine could not only reduce the IOP spikes but also their duration and both the combination and 1% apraclonidine had equal effect. However the use of oral acetzolamide 20 minutes prior to the intravitreal injection was not turn out to be effective.Evaluating the efficacy of timolol 0.5 % and brimonidine 0.2 % eye drops as a fixed combination in preventing IOP spikes Theoulakis et al found that twice a daylight instillation on the day before and before the time of injection in eyes which were scheduled for intravitreal ranibizumab was a safe and also effective in controlling the IOP spikes.IOP LOWERING MEDICATIONSMost of the IOP lowering medicines are administered topically. They are absorbed by dint of the cornea and conjunctiva mainly acting locally on the eye. many an(prenominal) anti glaucoma medicines have been utilise. The main groups of drugs are as followingBETA- ADRENERGICANTAGONISTSThey are the most prescribed drugs of IOP control. There are a total of quint topical beta-adrenergic antagonists which are currently FDA sanction for managing high intra ocular pressure. They are timolol betaxolol, carteolol, metipranolol, levobunolol . Betaxolol is selective beta1 selective antagonist, and is safe to use this drug in patients with pulmonary and cardiac problems.The mechanism of action is to reduce IOP by lessen the doing of sedimentary by inhibiting the production of cyclic adenosine monophosphate (cAMP) in ciliated epithelium. The IOP decline is upto 20 to 35%. The set up of beta blockers occur at heart an hour after its instillation. Timolol is available in the market in concentrations of 0.1%, 0.25% and 0.5%. The recommended back breaker is 1 drop two times a day. Burning, allergic reaction and corneal epithelial erosions are the main ocular side effectuate. It can be absorbed systemically and can cause systemic side cause like bronchospasm, bradycardia, hypotension, respiratory failure.Timolol maleate has a molecular weight of 432.50. It is an odorless, dust coat, filmy powder that is soluble in methanol, water and alcohol.It is deepen as an isotonic, sterile, buffered resolution available in tw o strengths 0.25% Timolol maleate eye drops contains 2.5 mg of timolol (about 3.4 mg of timolol maleate). It has a pH of approximately 7.0, and an osmolarity of 274-328 milliosmole. And each ml of 0.5% Timolol Maleate eye drops contains 5 mg of timolol (about 6.8 mg of timolol maleate). The Inactive ingredients are usually monobasic and dibasic sodium phosphate and sodium hydroxide to adjust pH. Preservative used is Benzalkonium chloride 0.01%.PARA SYMPATHOMIMETIC AGENTSThey act by stimulating sphincter pupillae and ciliary body by acting on the muscarinic receptors. They cause the contraction of the ciliary muscles which and so increases the aqueous outflow through the trabecular meshwork. Pilocarpine is the commercially available drug in this group and is compounded in concentration of 1%, 2%, 3%, and 4% and the recommended dosage is 1 drop 4 times per day.Ocular side make are miosis, induced myopia with brow ache, retinal detachment, and cataract. Systemic side effects after it s absorption can be of diarrhea, vomiting, abdominal cramps and bronchial spasm.CARBONIC ANHYDRASE INHIBITORS (CAIs)The enzyme required for aqueous validation is carbonic anhydrase. The CAIs cause banning of this enzyme and thus cause a decrease in the aqueous conception secretion by the ciliary epithelium. Carbonic anhydrase is required for catalyzing the reaction of carbon dioxide to H2CO3 which further splits into HCO3 _ and H+. The bicarbonate ions are pumped along with sodium ions into the posterior chamber along with diffusion of water for the formation of aqueous imagination.Carbonic anhydrase is defer in ciliary body in excess. 99.9 % of the enzyme must be inhibited before a significant decrease in IOP can occur. Dorzolamide and brinzolamide are the commercially available eye drops in market. They have a good corneal acuteness, and are also water soluble. These constituents are able to reduce IOP upto 14-17%. Adverse effects of topical CAIs are eager and stinging o f eyes on instillation, conjunctivitis, blephritis, corneal allergy, corneal punctuates keratitis and can also cause bitter taste.The systemic used CAIs are methazolamide and acetazolamide. They also cause inhibition of carbonic anhydrase in ciliary epithlium thus reducing the reduction of aqueous humor. As it is taken orally systemic side effects of CAIs include metabolic acidosis, leading to alkaline diuresis which result in hypokalemia. So potassium levels should be regularly checked in patients using CAIs on long term basis and oral potassium supplement should be recommended to all these patients. early(a) side effects include renal stones formation and central nervous system side effects like numbness and tingling of hands and feet, depression, anorexia, and nausea.Dorzolamide hydrochloride has a molecular weight of 360.91. It is a white to off-white in colour, in a crystalline powder form, which is also soluble in water, methanol and ethanol.ADRENERGIC AGONISTSAdrenergic ago nists act by increasing the uveoscleral and trabecular meshwork outflow thus causing decrease in IOP. Epinephrine has a mixed action of being an alpha and a beta agonist. Its effect usually begins at 1 hour and reaches a maximum at 2-6 hours. Topical epinephrine drops usage has been halt due to frequent systemic side effects of headache, palpitation and cardiac arrhythmias. The main ocular side effect is cystoid macular edema and black pigmentation of conjunctiva.commercially available topical form is dipivefrin hydrochloride 0.1%eye drops, which is a prodrug of epinephrine. It is converted by the enzyme esterase into epinephrine in the cornea. Because of its high lipid solubility and corneal penetration a low dose is required as compared to epinephrine and thus has less side effects.The selective alpha 2 agonist apraclonidine and brimonidine are indirect acting adrenergic agonist which act by decrease aqueous production and also the episcleral venous pressure and thus up(p) the t rabecular outflow. Apraclonidine is associated with tachyphylaxis while brimonidine has less of this problem. Brimonidine tartrate is available commercially in 0.25 and 0.15% eye drops. Its reduces IOP by 26% at 2 hour of interval.PROSTAGLANDIN ANALOGUESProstaglandin analogues are comparatively a new class of IOP lowering drugs. Four prostaglandin analogues have been approved by the FDA for clinical use. Latanoprost was the pioneer drug to be developed and used in this group. Others are travoprost, bimatoprost, and unoprostone.Latanoprost is a pro drug which penetrates the cornea and then is cancelled into active form. It enhances the uveoscleral outflow and thus lowers the IOP upto 25-35%. The dosage is one drop per day which makes the compliance of the patient better.The main ocular side effect is blackening of the iris and the periocular skin, by increase in the number of melanosomes in the melanocytes. Other side effects include conjunctival hyperemia, hypertrichosis, uveitis a nd cystoid macular edema. Systemic side effects are flu like symptoms, skin rash and uterine bleeding.osmotic AGENTSOsmotic agents act by decreasing the vitreous volume by removing the liquid out of the eye into the circulation. The osmotic agents can be accustomed orally or intravenously. Oral agent is glycerin while carbamide and mannitol are given intravenously.The osmotic activity is dependent upon the number of particles in the solution which cannot cross over and maintains the osmotic gradient among the compartments.Mannitol is given intravenously because it cannot be absorbed from the gastro-intestinal tract. A flinch increase in IOP and local tissue necrosis limit the use of urea.Glycerin is most commonly used oral osmotic agent which is given along with cracked ice to dilute its nauseating feeling. In patients with diabetes a non-metabolized sugar isosorbide can be used instead. some(prenominal) fixed combinations have been developed which are available in markets used f or IOP-lowering. Most of these fixed combinations contain timolol (dosed once or twice daily) combined with every adrenergic agonists, prostaglandin analogs, and CAIs.COMBINATIONFixed combination timolol maleate 0.5% with dorzolamide hydrochloride 2% was first introduced in market in 1998. Each milliliter of drug consisting of 6.83 mg timolol maleate and 22.26 mg dorzolamide hydrochloride.Timolol inhibits aqueous humor production by down-regulating adenylate cyclase by inhibiting 2-adrenergic receptor sites on the ciliary fulfil . While dorzolamide acts as a selective inhibitor of Carbonic anhydrase II enzyme, present on the ciliary process. The local bicarbonate production is slowed down, which as a result decreases sodium and fluid transport and, finally, decreases the aqueous humor production thus lowering the IOP. Because the mechanisms of action of both the drugs differ, they provide an additive effect when used together.Fixed combinations of drugs have been found to improve t he compliance of the patient by reducing the number of eye drops used daily. Moreover the IOP-lowering effect of fixed combination timolol and dorzolamide was found to be greater than that of either drug instilled as monotherapy. In addition the load of preservative is also reduced along with any wash out of drug when the drugs in monotherapy are instilled one after the other.