Iris IV ScStr - History

Iris IV ScStr - History


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

Iris IV

(ScStr: 1,923; 1. 321'0"; b. 39'0"; dr. 24'0"; s. 10 k.; cpl. 124; a. none)

The fourth Iris was built in 1885 by A. Leslie & Co., Newcastle, England, and was purchased by the Navy from AIiami Steamship Co. 25 May 1898 for service in the Spanish American War. However, reconditioning and conversion to a distilling ship was not completed until after the end of active operations ngainst Spain. Iris commissioned at Norfolk Navy Yard l Aug11st 1898, Lt. Arthur B. Connor in command.

The distilling ship departed Norfolk 31 August and arrived Montauk Point N.Y., 5 September. She departed New York Harbor 11 October for the Philippine Islands arriving 3Ianila 18 3Iarch 1899. She acted as a general utility ship for tile Asiatic Squadron in the Philippines during the occupation of the islands and during the subsequent insurrection. She decommissioned for repairs at Hong Kong 31 January 1900 and resumed duty in May.

Iris sailed for home in the fall of 1903 arriving San Francisco 13 November and decommissioning at Mare Island Navy Yard 18 December. She was overhauled there and placed in service as a collier for the Asiatic Squadron. For the next 5 years, she fueled United States vessels in the Orient.

She departed Manila 20 May 1909 for San Francisco where she `was converted to a torpedo boat tender. She was placed out of service15 October and decommissioned the same day. During the following years she serveded as parent ship for the Pacific Torpedo Fleet operating off the West Coast of the United States.

In the fall of 1915 disorder in Mexico threatened American citizens and interests. Iris arrived Topolobampo, Mexico 9 December to begin patrol duty on the Mexican coast. She remainod in the area ready to act in the event of any emergency until departing I,a Paz, Mexico, 30 Januarv 1916. She arrived San Diego, Calif. 4 February and began duty towing targets off southern California.

Two months later Iris was ordered to San Francisco. After arriving 16 April she decommissioned atMare Island 2 May 1916. Iris was transferred to the USSB 3 May 1917.


Coordination and Organometallic Chemistry

8.11.2 Classification of ET Reactions: Outer-Sphere, Inner-Sphere, Ion Transfer, Proton Transfer, and Catalytic and Noncatalytic Bond Breaking

ET reactions in polar solvents are always associated with internal or solvent-related molecular reorganization. 2 In fact, the thermal fluctuations in the reorganization of the bonds in the molecule itself or of its solvating sphere are the key factors in determining the activation barrier associated with ET. This idea was formulated quantitatively by Marcus, 3 and almost simultaneously by Levich and Dogonadze 4 , 5 in the 1950s. However, in many ET reactions, more than just solvent or ligand reorganization takes place. Bonds may break and new bonds may form, often in the presence of a catalyst. Moreover, in many practical cases in which the ET reaction takes place in water or other protic solvents, ET is often accompanied by proton transfer (PT). Before any detailed discussion of specific cases, it is useful to classify the different kinds of redox reactions, and to briefly discuss their theoretical modeling. 2 This section gives the classification the next section gives a succinct overview of the relevant theoretical concepts.

For the rest of this chapter, the terms ‘outer-sphere’ for the solvation sphere and ‘inner-sphere’ for all the intermolecular modes that reorganize during ET are used. These two types of ET reactions are pictured in a cartoon-like fashion in Figure 1(a) and 1(b) . Any ET event accommodated by the interaction with a catalyst (solid or molecular) will be referred to as catalytic ET. Note that in some of the electrochemistry and inorganic chemistry literature, catalytic ET is referred to as ‘inner-sphere’, but for the purpose of this chapter it will be useful to clearly distinguish between ‘inner-sphere’ and ‘catalytic’ ET. Reorganization within the inner sphere may be such that ligands dissociate, or even the reacting molecule dissociates, without a strong interaction with a catalyst. Such reactions will be referred to as bond-breaking electron transfer (BBET). A typical example is depicted in Figure 1(e) . Another type of electron or charge transfer reaction that is frequently encountered, especially in surface electrochemistry, is one in which the initial or final state of the reaction is bound to the electrode surface ( Figure 1(c) ). Such adsorption or discharge of ions will be referred to as ‘ion transfer’ the electrodeposition of metal ions onto a surface is a typical example. Somewhat related to ion transfer is PT, where the proton may either bind to the catalyst or to the reactant, and may or may not be concerted with ET. Figure 1(d) illustrates a typical situation where ET and PT happen simultaneously, with one of the states bound to the catalyst or the electrode surface. Catalytic reactions of interest in the chapter often involve ET, ion and/or PT, as well as bond breaking. They are multi-step ET reactions involving catalytic intermediates, as illustrated in Figure 1(f) .

Figure 1 . Cartoon-like illustrations of: (a) outer-sphere electron transfer (b) inner-sphere electron transfer (c) ion transfer (d) proton–electron transfer (e) bond-breaking electron transfer and (f) catalytic bond-breaking electron transfer.

The cartoons of the ET reactions as shown in Figure 1 are all taking place at an electrode (‘heterogeneous ET’). The electrode may be replaced by another redox partner to illustrate ‘homogeneous ET’. In the case of homogeneous catalytic ET, the electrode may be replaced by a molecular catalyst, but another redox couple is still needed to accept or donate the electrons for the redox reaction that is being catalyzed.


Causes

Fluid drains out of your eye through a system of canals. These canals live in a mesh of tissue between your iris (the colored part of your eye) and your cornea (the clear outer layer).

When your iris and cornea move closer together, it “closes the angle” between them. When this happens suddenly, it’s called an acute attack and is very painful.

Acute angle closure glaucoma completely blocks your canals. It stops fluid from flowing through them, kind of like a piece of paper sliding over a sink drain. The pressure that builds up can damage your optic nerve. If you don’t treat the problem quickly enough, you could lose your sight completely.

Continued

You might have an attack of angle closure glaucoma if you have narrow drainage systems and your eyes dilate (your pupil gets bigger) too much or too quickly. This can normally happen when you:

  • Go into a dark room
  • Get drops that dilate your eyes
  • Are excited or stressed
  • Take certain drugs like antidepressants, cold medications, or antihistamines

Some health conditions can also cause angle closure glaucoma:

Women are 2 to 4 times more likely to get it than men. You’re also more likely to have it if you’re:

  • Have a family history of it
  • Use medications that dilate your pupils
  • Use other medications that cause your iris and cornea to come together, like sulfonamides, topiramate, or phenothiazines

If you have acute angle closure glaucoma in one eye, you’re also more likely to get it in the other.


Methods

We have described the design of the trial previously. 3 In brief, eligible patients were 18 to 70 years of age and had previously untreated (except with hydroxyurea or anagrelide), Ph-positive CML in the chronic phase that had been diagnosed within 6 months before trial entry. Patients were randomly assigned to receive imatinib (at an oral dose of 400 mg per day) or interferon alfa (administered subcutaneously at a dose of 5 million IU per square meter of body-surface area daily) plus cytarabine (administered subcutaneously for 10 days every month at a dose of 20 mg per square meter daily) (see the protocol, available with the full text of this article at NEJM.org).

Crossover was allowed for lack of response (defined as no complete hematologic response by 6 months or no major cytogenetic response by 12 months response definitions are provided in the Methods section in the Supplementary Appendix, available at NEJM.org), disease progression (white-cell count, >20×10 9 per liter), loss of complete hematologic response or major cytogenetic response, unacceptable side effects, or reluctance to continue taking interferon alfa plus cytarabine after the trial results were released. After 7 years, the trial was extended for imatinib only. Patients in the group that received interferon alfa plus cytarabine were eligible to continue in the trial if they crossed over to imatinib.


These are ocular emergencies. They can be so severe as to damage the pluripotent limbal stem cell, leading to opacification and neo-vascularisation of the cornea and to extensive scarring.

Acid burns

Acids precipitate tissue protein, creating a barrier to further ocular penetration, so they tend to be less severe than alkali injuries. An exception is hydrofluoric acid (used in glass polishing), which rapidly passes through cell membranes and enters the anterior chamber of the eye, where it reacts with collagen and causes a rapid increase in intraocular pressure.

  • Common causes of acid injury are: sulfuric acid (car batteries), sulfurous acid (bleach), acetic acid (vinegar), hydrochloric acid (swimming pools) and hydrofluoric acid (glass polishing).

Alkali burns

Alkali burns are generally more severe and cause penetrating eye injuries. They cause corneal damage by pH change, ulceration, proteolysis and collagen synthesis defects. Alkalis are liphophilic and penetrate the eye much more rapidly than acids. They can quickly deposit within the tissues of the ocular surface, leading to saponification. The inflammatory response from the damaged tissue leads to further damage. Alkali can penetrate into the anterior chamber, causing cataract formation and damage to the ciliary body and trabecular meshwork.

  • Common causes of alkali injury are: ammonia (fertilisers, refrigerants), potassium hydroxide (potash), sodium hydroxide (drain cleaners, car airbags), magnesium hydroxide (sparklers, flares) and lye (plaster, mortar, cement, whitewash). The alkali aerosol in car airbags can be released even if the bag does not rupture.

Presentation

  • Pain, blurring, photophobia, FB sensation.
  • Blepharospasm, red eye, cloudy cornea. NB: the eye may not be red if a severe burn causes ischaemia of conjunctival vessels.

Management [10]

A chemical burn needs urgent irrigation before pausing for history or examination. Manage immediately, using three "I"s: IRRIGATE, IRRIGATE and IRRIGATE. This may be the single most important factor in determining visual outcome.

  • Copious irrigation is crucial using isotonic saline or lactate ringer solution (if you have neither, use water).
  • Local anaesthetic drops may be necessary in order to allow eye opening for irrigation.
  • 20 L or more may be required to change pH to physiological levels.
  • pH testing should be done - normal pH of the eye is 7.4. Once pH is neutralised, the eye can be examined and the patient transferred to specialist care.
  • If the chemical contains particles, the lids should be spread widely, irrigation continued and a cotton bud used to lift out particles.
  • If you need topical anaesthetic to help keep the eye open, add a drop every five minutes (as this will be washed away too).
  • If non-sterile water is the only liquid available, it should be used.
  • Refer the patient urgently while continuing irrigation.
  • Whilst irrigating, obtain history, including chemical used and any thermal or blast injury (which may cause penetrating FBs as well as a burns). Specific information on poisons is available from the National Poisons Information Service.

How to irrigate following chemical eye injury

  • A number of saline bags, a giving set and towels are needed.
  • Sit the patient by a sink. Instil anaesthetic drops and gently tilt the patient's head back so that they are holding it over the rim of the sink, explaining what you are going to do (this is easy to forget in the rush - irrigation can be unpleasant in the first few moments, until a steady stream is achieved).
  • Remove contact lenses if present [6] .
  • Use a 500 ml bag of saline and empty it into the conjunctival sac, using a purpose-built irrigator if you have one - or through a standard giving set (cut the end of the tubing if necessary to deliver the fluid more quickly).
  • Ensure that both upper and lower fornices are irrigated. As a rough guide, check the pH between bag change-overs.
  • You will need several bags the volume required to reach a neutral pH varies but may be up to 20 L in severe cases, particularly where alkalis are involved.
  • Carry on for 15-30 minutes at least, checking pH every five minutes or so.
  • After irrigation, acuity should be recorded and the surface of the eye stained to look for epithelial defects.
  • Note that CS gas injuries are treated differently to other chemical eye injuries, by blowing cool air on to the eyes (see under 'Deterrent spray injuries', below).

Further management

  • Acute-phase treatment includes a broad-spectrum topical antibiotic, and cycloplegic and anti-glaucoma therapy. Various therapies to promote re-epithelisation, support repair and control inflammation are used, including tear substitutes, ascorbic or citric acid, and acetylcysteine and bandage soft contact lenses. Steroids are used cautiously.
  • After chemical injury, the goal is to restore a normal ocular surface and clarity. If extensive corneal scarring is present, surgical debridement, limbal stem cell grafting, amniotic membrane transplantation and keratoprosthesis can help restore vision.

Managing the Narrow-angle Patient

Currently, most physicians use a combination of an argon and an Nd:YAG laser for their peripheral laser iridotomies, especially in dark and thick irides. This approach consists of thinning the target area with the argon beam, then using the Nd:YAG laser to open the hole in the iris.

It's a good idea to pretreat patient with an alpha-agonist such as brimonidine to help avert postoperative IOP spikes. We also recommend pretreating the patient with a drop of pilocarpine 1-2% to constrict the pupil and place the iris on stretch. Placing the iridotomy at either 11 or 1 o'clock is often helpful placing the iridotomy hole directly at 12 o'clock can cause the surgeon's view to be inadvertently obstructed by bubbles that form during the procedure.

The lid position is also crucial, since the surgeon would like the iridotomy placed superiorly enough for the hole to be covered by the upper lid. An adverse event glaucoma specialists greatly fear after prophylactic laser iridotomy is the ghost or double image resulting from the lid not fully covering the iridotomy hole.

The main complications associated with laser iridotomy are cataract, IOP spikes, significant transient inflammation and ghost images.

• Laser settings. The range of argon laser powers differs depending on the method applied (i.e., either thinning or punching technique). For the punch technique, most practitioners use between 800 and 1,200 mW, with a duration of 0.1 to 0.2 seconds. For the thinning technique, lower powers and longer duration are required, usually 200-400 mW for 0.2 to 0.5 seconds.

The range employed with the Nd:YAG laser depends on whether or not the iris tissue has already been thinned with the argon laser. Most practitioners use between 3-7 mJ and one or two pulses (lower powers of 4-5 mJ are used if the iris tissue has already been thinned with the argon laser).

After the procedure, most physicians recheck the IOP in an hour to rule out an IOP spike. If this occurs, it needs to be addressed with medical therapy and, on rare occasions, surgery. Finally, prescribe a topical steroid for the first few days afterward to alleviate any mild inflammation. 1 A postop course of an alpha-agonist will continue the protection against pressure spikes.


Fenton Autumn Acorns Bowl

This marigold-colored autumn acorns bowl was made by Fenton, which is one of the most prolific names in American glassware. Marigold is one of the most common carnival glass colors.

Fenton's carnival glass was first marketed as the "golden sunset iridescent assortment" in catalogs. In 1907 when these pieces first sold, they cost 85 cents. A Fenton autumn acorns bowl averages for about $65. You can find some selling for as much as $150. Earlier Fenton specimens, up through 1920, can fetch a high price.

The rage for carnival glass in the United States continued for 10 years (1908 to about 1918). When the market for carnival glass slumped in the 1920s, the lower-quality carnival glass was given away as prizes at carnivals.

Fenton was a family-owned business operating from 1905 through 2011. It made carnival glass in many different colors.


Background and early years of reign

Ramses’ family, of nonroyal origin, came to power some decades after the reign of the religious reformer Akhenaton (Amenhotep IV, 1353–36 bce ) and set about restoring Egyptian power in Asia, which had declined under Akhenaton and his successor, Tutankhamen. Ramses’ father, Seti I, subdued a number of rebellious princes in Palestine and southern Syria and waged war on the Hittites of Anatolia in order to recover those provinces in the north that during the recent troubles had passed from Egyptian to Hittite control. Seti achieved some success against the Hittites at first, but his gains were only temporary, for at the end of his reign the enemy was firmly established on the Orontes River at Kadesh, a strong fortress defended by the river, which became the key to their southern frontier.

During his reign Seti gave the crown prince Ramses, the future Ramses II, a special status as regent. Seti provided him with a kingly household and harem, and the young prince accompanied his father on his campaigns, so that when he came to sole rule he already had experience of kingship and of war. It is noteworthy that Ramses was designated as successor at an unusually young age, as if to ensure that he would in fact succeed to the throne. He ranked as a captain of the army while still only 10 years old at that age his rank must surely have been honorific, though he may well have been receiving military training.

Because his family’s home was in the Nile River delta, and in order to have a convenient base for campaigns in Asia, Ramses built for himself a full-scale residence city called Per Ramessu (“House of Ramses” biblical Raamses), which was famous for its beautiful layout, with gardens, orchards, and pleasant waters. Each of its four quarters had its own presiding deity: Amon in the west, Seth in the south, the royal cobra goddess, Wadjet, in the north, and, significantly, the Syrian goddess Astarte in the east. A vogue for Asian deities had grown up in Egypt, and Ramses himself had distinct leanings in that direction.

The first public act of Ramses after his accession to sole rule was to visit Thebes, the southern capital, for the great religious festival of Opet, when the god Amon of Karnak made a state visit in his ceremonial barge to the Temple of Luxor. When returning to his home in the north, the king broke his journey at Abydos to worship Osiris and to arrange for the resumption of work on the great temple founded there by his father, which had been interrupted by the old king’s death. He also took the opportunity to appoint as the new high priest of Amon at Thebes a man named Nebwenenef, high priest of Anhur at nearby This (Thinis).


Iris IV ScStr - History

This site is governed solely by applicable U.S. laws and governmental regulations. Please see our Privacy Policy. Use of this site constitutes your consent to application of such laws and regulations and to our Privacy Policy. Your use of the information on this site is subject to the terms of our Legal Notice. You should view the News section and the most recent SEC Filings in the Investor section in order to receive the most current information made available by Johnson & Johnson Services, Inc. Contact Us with any questions or search this site for more information.

alt alt alt alt alt alt alt alt alt alt alt alt alt alt alt alt alt alt

Medical therapy

The medications currently used to treat glaucoma work by lowering the intraocular pressure by two main mechanisms 1) reducing aqueous humor production and/or 2) increasing aqueous humor outflow.

Medications that suppress aqueous humor production

Beta Blockers

Mechanism of action

Lower IOP by suppressing aqueous humor production. They inhibit synthesis of cyclic adenosine monophosphate (c-AMP) in the ciliary epithelium and lead to a decrease in aqueous secretion.

Side Effects

Ocular side effects of topical beta-blockers are minor and include burning and decreased corneal sensation. Systemic side effects can be more severe. They include bradycardia arrhythmia heart failure heart block syncope bronchospasm or airway obstruction central nervous system effects (depression, weakness, fatigue, or hallucinations) impotence, and elevation of blood cholesterol levels. Topical beta-blockers have been shown to decrease HDL and increase cholesterol. Diabetics may experience reduced glucose tolerance and hypoglycemic signs and symptoms can be masked. Beta-blockers may aggravate myasthenia gravis and abrupt withdrawal can exacerbate symptoms of hyperthyroidism. The beta-1 selective antagonist, betaxolol, has fewer pulmonary side effects.

Adrenergic Agonists

Mechanism of action

Lower IOP through alpha 2 agonist mediated aqueous suppression and a secondary mechanism that increases aqueous outflow.

  • Nonselective adrenergic agonists such as epinephrine lower IOP by several different mechanisms. Initially, a vasoconstrictive effect decreases aqueous production and c-AMP synthesis increases the outflow facility.
Side Effects

Ocular side effects include follicular conjunctivitis, burning, reactive hyperemia, adrenochrome deposits, mydriasis, maculopathy in aphakic eyes, corneal endothelial damage, and ocular hypoxia. Systemic side effects include hypertension, tachycardia and arrhythmia. Dipivefrin is a prodrug that is hydrolyzed to epinephrine as it traverses the cornea. It has significantly fewer systemic side effects than epinephrine. The potential side effects of nonselective adrenergic agonists has led to decline in their use.

Selective adrenergic agonists

  • include apraclonidine and brimonidine (0.1-0.2%) with the latter having much greater selectivity at the alpha 2 receptor.

Brimonidine (0.1-0.2%) appears to also increase uveoscleral outflow and lower IOP by about 26%.

Side Effects of selective adrenergic agonists

Common ocular side effects include contact dermatitis (40% with apraclonidine, < 15% for brimonidine, and <0.2% for brimonidine-Purite), follicular conjunctivitis, eyelid retraction, mydriasis, and conjunctival blanching. Systemically, they can cause headache, dry mouth, fatigue, bradycardia, and hypotension. Long-term use of topical apraclonidine is frequently associated with allergy and tachyphylaxis. The use of brimonidine is contraindicated in infants and young children (especially those with low body weight) due to an increased risk of somnolence, hypotension, seizures, and apnea, believed to be due to increased CNS penetration of the drug secondary to high lipophilicity. Generally, brimonidine seems to produce fewer ocular side effects than apraclonidine.

Carbonic Anhydrase Inhibitors (CAI)

Mechanism of action

Lower IOP by decreasing aqueous production by direct antagonist activity on the ciliary epithelial carbonic anhydrase. Over 90% of ciliary epithelial enzyme activity needs to be abolished to decrease aqueous production and lower IOP. Systemic CAI include acetazolamide (Diamox) and methazolamide (Neptazane). Topical CAIs include brinzolamide 1% (Azopt) and dorzolamide 2% (Trusopt). A 14-17% reduction in IOP is seen with these agents. 

Side Effects

Systemic CAIs are associated with numerous side effects, including transient myopia paresthesia of the fingers, toes, and perioral area urinary frequency metabolic acidosis malaise fatigue weight loss depression potassium depletion gastrointestinal symptoms renal calculi formation and rarely, blood dyscrasia. Due to the side effects of the systemic CAIs, they are most useful in acute situations or as a temporizing measure before surgical intervention. The topical CAIs have significantly fewer systemic side effects than oral carbonic anhydrase inhibitors and have been reported to have clinical efficacy comparable to that of timolol. Common side effects of topical CAIs include bitter taste, blurred vision, punctate keratopathy, and lethargy.

Medications that increase aqueous outflow

Prostaglandin Analogs

Mechanism of action

Lower IOP by increasing aqueous outflow through the unconventional outflow pathway or uveoscleral outflow.  The exact mechanism by which prostaglandins improve uveoscleral outflow is not full understood, but may involve relaxation of the ciliary muscle and remodelling of the extracellular matrix elements of the ciliary muscle. These agents have been shown to increase the outflow by as much as 50%.

Latanoprost and travaprost, and bimataprost (prostamide), represent the newest, the most effective, and most commonly used class of medications.  Latanoprost 0.005% and travaprost 0.004% are pro-drugs that penetrate the cornea and become biologically active after being hydrolyzed by corneal esterases. Bimataprost 0.03% decreases IOP by increasing uveoscleral outflow by 50% and increasing trabecular outflow by approximately 25-30%. Both latanoprost and travaprost reduce IOP by approximately 25-30%.

Side Effects

Ocular and systemic side effects such as conjunctival injection, hypertrichosis, trichiasis, hyperpigmentation of periocular skin and hair growth around the eyes are generally were well-tolerated. These tend to be reversible with cessation of the drug. A unique side effect is increased iris pigmentation which is thought to be secondary to increased melanin content in the iris stromal mealnocytes without proliferation of cells. This tends to occur in 10-20% of blue irides within 18-24 months of initiating therapy, and 60% eyes with mixed green-brown or blue-brown irides. Use of prostaglandin analogs and prostamides have also been associated with exacerbations of herpes keratitis, anterior uveitis, and cystoid macular edema in susceptible individuals. Photos Courtesy of Anjana Jindal, MD, Wills Eye Hospital

Parasympathomimetic Agonists

Mechanism of action

Lower IOP by increasing aqueous outflow related to contraction of the ciliary muscle in eyes with open angles and pupillary constriction in cases of pupillary block glaucoma.

Topical cholinergic agonists such as pilocarpine cause contraction of the longitudinal ciliary muscle, which pulls the scleral spur to tighten the trabecular meshwork, increasing outflow of aqueous humor. This results in a 15-25% reduction in IOP. The direct agents (pilocarpine) are cholinergic receptor agonists the indirect agents (echothiophate iodide) inhibit cholinesterase and prolong the action of native acetylcholine. Carbachol is a mixed direct agonist/acetylcholine releasing agent.

Side Effects

Systemic side effects of pilocarpine are rare however, ocular side effects are common. Ocular side effects include brow ache, induced myopia, miosis (leading to decreased vision), shallowing of the anterior chamber, retinal detachment, corneal endothelial toxicity, breakdown of the blood-brain barrier, hypersensitivity or toxic reaction, cicatricial pemphigoid of the conjunctiva, and atypical band keratopathy. The indirect agents have ocular side effects that are generally more intense than those of the direct agents. In addition, indirect agents can cause iris cysts in children and cataract in adults. Finally, prolonged respiratory paralysis may occur during general anesthesia in patients who are on cholinesterase inhibitors because of their inability to metabolize paralytic agents such as succinylcholine. The use of cholinergic agents has declined in recent years with the availability of newer medications that have comparable efficacy and fewer side effects.

Rho kinase inhibitor

Mechanism of action

Netarsudil 0.02% (Rhopressa Aerie Pharmaceuticals) was approved by the Food and Drug Administration (FDA) in 2017 as the first Rho kinase inhibitor for the treatment of OAG or ocular hypertension. Netarsudil increases aqueous outflow through the trabecular meshwork and decreases episcleral venous pressure by inhibiting the effect of Rho kinase on actin and myosin contraction. In the ROCKET clinical trials, once daily netarsudil was found to be noninferior to twice daily timolol, reducing IOP by an average of about 4mmHg. Netarsudil may have a particularly important role in treating patients with lower starting IOPs. In addition to its action on the trabecular meshwork to increase outflow, netarsudil’s unique ability to lower episcleral venous pressure can achieve a target beyond the low teens, which is otherwise difficult to achieve with a venous back pressure in the 8-12mmHg range. 

In 2019, the FDA approved the combination of netarsudil with latanoprost as a once-daily medication for the treatment of OAG or ocular hypertension (Rocklatan Aerie Pharmaceuticals: netarsudil and latanoprost ophthalmic solution 0.02%/0.005%). In the MERCURY clinical trials, more than 60% of enrolled patients taking the combination medication achieved an IOP reduction of 30% or more compared to about 30% achieving this target on latanoprost monotherapy.

Side Effects

Netarsudil has a favorable safely profile. Most commonly reported side effects include conjunctival hyperemia (50%), corneal verticillata (20%), and conjunctival hemorrhage (20%). While clinical evident on biomicroscopic exam within the first 4 weeks of treatment, corneal verticillata have not been found to be functionally or visually significant. Most corneal verticillata resolved upon discontinuation of treatment. 

Nitric Oxide

Mechanism of action

Latanoprostene bunod 0.024% (Vyzulta Bausch+Laumb) was approved for reduction of IOP in OAG or ocular hypertension by the FDA in 2017, filling a niche by combining the effects of a prostaglandin analog with the action of nitric oxide on the trabecular meshwork outflow. Nitric oxide (NO) levels are known to be lower in glaucomatous eyes, and NO deficiency may lead to trabecular contraction and decreased outflow facility. Additionally, when instilled into the eye, NO diffuses to the trabecular meshwork to promote cell relaxation and increase outflow to lower IOP. Latanoprostene bunod leverages these effects of NO by releasing the molecule upon metabolizing in the eye. In the VOYAGER study, patients receiving latanoprostene bunod had an average of 1.23mmHg lower reduction in IOP compared to patients receiving latanoprost alone. 

Side Effects

The safety profile of latanoprostene bunod is similar to that of other prostaglandin analogs, including increase iris and periorbital skin pigmentation and eyelash growth. Caution should be used in patients with a history of intraocular inflammation or macular edema. The most common adverse effects reported are conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and pain at the instillation site (2%).

Combination medications

Fixed combination medications offer the potential advantage of increased convenience, compliance, efficacy, and cost. Some fixed-combination medications currently on the market in the US include: dorzolamide hydrochloride 2% and timolol maleate ophthalmic solution 0.5% (Cosopt, now available as generic), brimonidine tartrate 0.2%, timolol maleate ophthalmic solution 0.5% (Combigan), brimonidine tartrate 0.2% and brinzolamide 1% (Simbrinza), and netarsudil and latanoprost ophthalmic solution 0.02%/0.005% (Rocklatan). Prior to initiating monotherapy with a fixed-combination medication, it is important to prove the efficacy of the individual components of the medications. The efficacy and ocular side effects for both fixed-combination medications are similar to their individual components. The efficacy and tolerability of both dorzolamide hydrochloride-timolol maleate 2%/0.5% and brimonidine tartrate-timolol maleate 0.2%/0.5% appear to be similar to each other.

Hyperosmotic agents

Hyperosmotic agents such as oral glycerine and intravenous mannitol can rapidly lower IOP by decreasing vitreous volume. They do not cross the blood-ocular barrier and therefore exert oncotic pressure that dehydrates the vitreous. Side effects associated with the hyperosmotic agents can be severe and include headache, back pain, diuresis, circulatory overload with angina, pulmonary edema and heart failure, and central nervous system effects such as obtundation, seizure, and cerebral hemorrhage. Because of these potentially serious side effects, they are not used as long-term agents. They are typically used in acute situations to temporarily reduce high IOP until more definitive treatments can be rendered.

Summary of glaucoma medications

Increase in iris pigment (particularly in hazel iris), cystoid macular edema, hypertrichosis, conjunctival injection, keratitis, and uveitis


Watch the video: Infective uveitis 1 Syphilis, Toxoplasmosis, viral


Comments:

  1. Ahiga

    I'm at last, I apologize, it's not the right answer. Who else can say what?

  2. Tyce

    chin up

  3. Tedric

    At all personnel depart today?

  4. Zologor

    It is simply excellent idea

  5. Randell

    It is cleared

  6. Naaman

    This topic is just amazing :), very interesting to me)))



Write a message