Ординатура / Офтальмология / Английские материалы / Pediatric Opthalmology_Mukherjee_2005

Management consists of control of uveitis, lowering of intraocular tension to a safe limit and removal of lens.

Chemical injuries as cause of glaucoma83. Both types of chemicals i.e. alkali or acids cause initial rise of tension for first few hours to few days, then it comes to normal. This initial rise of tension is attributed to shrinkage of sclera and cornea and release of prostaglandin.80 This phase is followed by return to normal tension. The tension may be established within normal range and remain so but in many eyes there is rise of tension due to continued action of prostaglandin, uveitis and tissue disruption brought about by action of the chemicals.

Management consists of immediate management of chemical burn by standard method, administration of carbonic anhydrase inhibitors for short period. Local betablockers and alpha agonist. Miotics are contra indicated. Frequent instillation of steroids reduces uveitis, if tension is not controlled a fistulising surgery with anti metabolites may be required. In some cases glaucoma implants may be the last resort.

Tumour related glaucoma84, 85, 86. All types of intraocular tumours, benign or malignant cause glaucoma. In adults common tumours producing glaucoma are related to uvea, followed by intruocular metastases. In children the common tumours causing glaucoma are retinoblastoma81,82, diktyomo, juvenile xanthogranuloma, leukaemia. Benign hamartomas that produce glaucoma are von Recklinghausen’s syndrome and Sturge Weber syndrome. Glaucoma by Sturge Weber syndrome inflicts children while that due to Von Recklinghausen’s syndrome causes glaucoma in young adults.

Tumour related glaucoma are generally unilateral. They can cause both open angle as well as narrow angle glaucoma with or without pupillary block.

Severity of glaucoma depends on size, location and duration of the growth.

Common causes of tumour related glaucoma are86 :

(a) Direct infiltration of the angle by tumour.

(b) The eyes have associated congenital anomalies (phacomatosis).

(c) Angle may be blocked by tumour cells present in anterior chamber as pseudohypopyon (Retinoblastoma).

(d) The iris lens diaphragm may be pushed by a large tumour mass. (e) Neovascularisation of angle (Retinoblastoma).

(f ) Raised episcleral pressure.

All eyes with unexplained unilateral rise of intraocular tension should be examined well, to exclude possibility of intraocular tumour by, indirect ophthalmoscope, gonioscope and ultrasonography.

Management of tumour related glaucoma is essentially treatment of primary cause specially if it is life threatening like retinoblastoma or leukaemia.

Neovascular glaucoma. Neovascular glaucoma in children is far less common than neovascular glaucoma in adults. Diabetic retinopathy and central vein thrombosis are two causes that top the long list of causes in adults.87, 88 These conditions are not seen in children. Common causes of neovascularisation glaucoma in children are retinoblastoma, Coat’s

disease, retrolental fibroplasis. Neovascular glaucoma can be either open angle or closed angle secondary glaucoma.

Management of neovascular glaucoma in children is as difficult as in adult and does not differ much. Miotics are contra indicated. Tension should be brought down by betablockers or alpha agonist. Local steroids and cycloplegics help to reduce associated inflammation.

Filtering surgeries are not very effective. Best results are cyclodestructive procedures i.e. transcleral cyclocryo, and Nd-YAG cyclophto coagulation.

Glaucomcyclitis crisis. This is rarely seen in children. It may present as unilateral periodic rise of tension in late teens with signs of cyclitis. The affected pupil is larger than the other. There are signs of cyclitis. The rise of tension is periodic. Each episode may last from few hours to few weeks. During crisis the tension may reach between 40 mm to 60 mm coming down even without treatment89. Persistent raised tension is controlled by betablockers. Associated uveitis is treated by local steroids and rarely by mydriatic. Surgery is contra indicated.

EPIDEMIC DROPSY GLAUCOMA90, 91, 92, 93

Epidemic dropsy is an acute toxic systemic condition with multi-systemic involvement seen as epidemics in certain areas of the world. The endemic countries are mostly located in South East Asia, Fiji and South Africa. Worst effected country is India, specially eastern and northeastern states where mustard oil is used as cooking media or anoint. Epidemics have been reported from other parts of India from time to time outside the endemic state.

Mustard oil itself does not cause the diseases. Epidemic dropsy occurs only when edible oil even other than mustard oil gets contaminated by oil of argemone mexicana (yellow prickly poppy) that grows as weed with mustard plants. Mustard oil may be adulterated intentionally or may be contaminated accidentally95, 96, 97.

Argemone mexicana contains sangunarine and dihydro sangunarine that cause rise in blood pyruvate level which is thought to be the cause of the disease93. Ocular symptoms are late to develop following systemic involvement.

Systemic features are94, 95

1.Warm erythromatous, tender, hypopigmented skin lesions.

2.Pitting edema of feet and legs.

3.Non specific cardiac failure leading to dyspnea.

4.Diarrhea.

5.Malaise and fever.

In severe cases the condition can be fatal due to cardiac failure.

Ocular signs and symptoms develops six to eight weeks after development of pedal edema. Glaucoma develops mostly after subsidence of systemic signs and symptoms.

Glaucoma in epidemic dropsy is bilateral, involving both the sexes. No age is immune. Children in first decade may not be affected. It is as common in children in second decade as in adults.

The glaucoma is wide angle glaucoma, with normal chamber and angle. Outflow is within normal limits. The aqueous shows raised level of histamine, prostaglandin and protein suggesting that the glaucoma is hypersecretory. There is no anterior chamber reaction. The eye is white, cornea may show haze due to rise of intraocular tension that may be as high as 60 to 80 mm Hg. The patient may only complain of irritation of the eye, coloured haloes, round the light which is marked and persistent. The disc and field changes are similar to those seen in chronic simple glaucoma.

The exact mode of hypersecretion is not known, it is said to be of central origin. Other ocular findings are toxic vasculitis, venous dilatation and superficial haemorrhages. In milder form the systemic features subside with discontinuation of adulterated oil from diet. It is worth noting that epidemic dropsy can be caused by consuming other vegetable oils that have been adulterated not only by argemone maxicana but also other chemicals like some mineral oils.

Glaucoma starts late and may linger on for long time. It is partly self limiting. Even when it subsides with or without treatment it leaves stigma in the form of glaucomatous disc and corresponding field changes. All patients with juvenile chronic simple glaucoma should be asked about their food habits specially about cooking medium.

Management. Glaucoma being hypersecretory does not respond to pilocarpine. Drugs that reduce aqueous formation like epinephrine, its product dipivefrin give better results. Topical beta-blockers also give favourable results. Systemic acetazolamide is employed for short term relief. Systemic indomethasin is used as adjunct with topical drops.

It takes few weeks to months to bring the tension to normal range. Once this has been reached the drugs are gradually withdrawn and maintained on minimum dose. The patients are followed up twice a year for next two to three years.

If tension can not be brought down, by medical treatment any of the standard filtering surgeries can be employed.

Juvenile primary open angle glaucoma98. Juvenile glaucoma is a non specific term used to designate a large group of conditions that cause rise of intraocular tension in a patient after three years of age and before third decade.

Most of these conditions are secondary or associated glaucomas30, 31, 32. These may be wide or narrow angled. In some cases pupillary block may be present. In contrast to above conditions juvenile primary open glaucoma is a term that designates a specific disorder, which is similar clinically to adult primary open angle glaucoma with a distinct genetic predisposition98.

Some people consider juvenile primary open angle glaucoma to be the late onset of congenital glaucoma where trabecular meshwork was not obstructed enough to cause rise of intraocular tension before three years and was not open enough to maintain normal outflow after three years. Others postulate that the condition is early onset of adult primary open angle glaucoma.

Incidence of juvenile primary open angle glaucoma is far less than its secondary counterparts, commonest age of diagnosis is eighteen years. The range being eight to thirty years. The condition is bilateral. There may be a history of P.O.A.G. or myopia in the family. The condition is autosomal dominant. It is more often missed than diagnosed till it is advanced.

The cornea77 is devoid of stigma of congenital open angle primary glaucoma, or traces of mesodermal dysgenesis. Only suspicious corneal change may be an enlarged cornea.

There is no evidence of trauma, uveitis or use of steroids.

The children are brought only for diminished vision. On examination the child may be myope. Positive signs that warrant measuring of intraocular tension are changes in the optic nerve head. There may be asymmetry of the cup, notching of the cup, change in CD ratio. Tension can be recorded under local anaesthesia either by Schiotz’s tonometer or handheld applanation tonometer in children as young as six years provided the child is explained that the procedure is painless, but is an essential procedure for treatment. Generally the child is more co-operative during subsequent visits. No touch tonometer is better alternative.

The tension may be as high as 40-50 mm kg. The anterior chamber is clear with normal depth, the angle is wide without any uveal tags, synaechia or pigments. The field changes are similar to those seen in adult primary wide angle glaucoma.

Treatment :

The principle and mode of management is same i.e. medical/surgical as in adults. I. Medical treatment consists of

(a) Local instillation of 1. Direct acting miotics, 2. Beta blockers, 3. Alpha agonist, 4. Epinephrine and dipiveprin, 5. Local carbonic anhydrase inhibitor.

(b) Systemic carbonic anhydrase inhibitors for short term.

II.Surgical treatment—Surgery is indicated if local treatment fails to keep the tension within normal range.

1.Goniotomy has uniformly poor result over three years of age.

2.Trabeculectomy gives better results. However the results are not as good as in adults because children have increased tendency for subconjunctival fibrosis that obliterate the opening. The fibrosis can be minimized by use of antimetabolites.

Besides keeping intraocular tension within normal range and stabilising the field changes, the child’s refractive error should also get due importance. These children are invariably myopes. There is always a change towards myopic astigmatism following filtering surgery. Uniocular poor vision usually produces amblyopia that should be managed by standard procedures.

Outline of various modes of management of glaucoma. Aim of management of glaucoma is to lower the intraocular tension, to make it compatible with vision and stop the progress of field and fundus changes. Fundus changes are reversible under three years of age.

This can be brought about by :

A.Medical treatment

B.Surgical treatment

C.Non invasive physical methods

A.Medical treatment comprises of 1. Local drops

2. Systemic drugs

Medical treatment

1.Local drops mostly act on autonomic nervous system either as agonist or antagonist can either be :

(a) Parasympathomimetic99, 100, 105 : (i) Direct acting

(ii) Indirect acting (iii) Combined

(b) Beta blockers :

Non selective. These block both beta one and beta two receptors.

Selective. These are also called cardio selective. They are more potent beta one blocker than beta two.

(c) Sympatho-mimetics, they can be : (i) Alpha adrenergic agonists (ii) Beta adrenergic agonists

(Adrenergic antagonists are no more in vogue in management of glaucoma) (d) Prostaglandin analogue (analogs) Latanoprost

(e) Prostamides (Lumigan—Bimatoprost .005%) (f ) Other ocular hypotensive lipids

(g) Local carbonic anhydrase inhibitors : (i) Short acting CAI

(ii) Delayed acting CAI.

2.Systemic drugs

(a) Carbonic anhydrase inhibitors (i) Short acting

1.Oral labels

2.Injectables

(ii) Delayed acting (b) Hyperosmotic agents

(i) Oral —glycerol —Isosorbide

(ii) Injectable —Mannitol —Urea

The anti-glaucoma drugs can be put in two groups i.e.

(i) Those reduce formation of aqueous (ii) Those that increase outflow.

The drugs that decrease formation of aqueous are Beta blockers, epinephrine, depivprin, apraclonidine, brimonidine and C.A.I.

Those that increase outflow are : Miotics, epinephrine, depiveprin, brimonidine and latanoprost.

Hyper osmotic agents are altogether different from above two groups, they act by increasing blood osmolarity and drawing water from vitreous.

Direct acting parasympathomimetic drugs. Pliocarpine is an alkaloid100 used either as nitrate or chloride in strength of 1% to 2% and rarely 4%. Percentage higher than 4% do not have any additional advantage however side effects increase with increased concentration. It has best IOP lowering effect at pH 6.5. Pilocarpine is mostly used as drops102. However it can be used as gel, ointment, ocuserts and soft contact lens soaked in pilocarpine101, 102. Action of pilocarpine starts with in 20 minutes and passes off in 4 hours. Stronger solutions have more prolonged effect. Hence drops in lower strength have to be used more frequently, action of gel and ocusert last longer than aqueous solution. Addition of betablockers and alpha agonist have synergistic effect on pilocarpine and vice versa. Pilocarpine when used alone has to be instilled four times a day. This frequency is reduced to twice a day when used with beta blockers or alpha agonist.

Pilocarpine acts directly on cholenergic receptors. Most visible action of pilocarpine is miosis. It also causes cyclotonia, increasing ciliary tone. Cyclotonia and miosis are inseparable but they lower IOP in two different ways. Miosis is effective in lowering IOP by pulling the iris away from the trabecular meshwork thus opening a mechanically closed angle in primary closed angle glaucoma. The miosis has an adverse effect i.e. pupillary block. Synecheal blocks are however not relieved by pilocarpine.

In primary open angle glaucoma, pilocarpine contracts the longitudinal fibres of ciliary body which being anchored to scleral spur, automatically pull the scleral spur and trabecular meshwork, opening the meshwork thus increasing aqueous outflow.

Pilocarpine in no way acts on production of aqueous. It has an adverse effect on uveoscleral outflow. Hence pilocarpine is contra indicated in permanent secondary angle closure. Frequent instillation of pilocarpine increases permeability of uvea blood vessels leading to derangement of blood aqueous barrier. This results in plasmoid aqueous rendering pilocarpine unsuitable in inflammatory and neovascular glaucoma. Pilocarpine has no role in buphthalmos.

Adverse effects of pilocarpine are local as well as systemic. Side effects depend upon strength, frequency, duration and amount of systemic absorption. Immediate local side effects is burning in the conjunctiva. This is pH dependent, lesser the pH more is the sting, pH 6.5 to 7.5 is better tolerated than ph 4.0.

Conjunctival congestion, miosis and spasm of accommodation are other local side effects.

Miosis leads to following adverse effects. Distant vision is drastically reduced in presence of central corneal and lenticular opacities, night vision is diminished due to nondilatation of pupil in dark. Generally there is constriction of peripheral field and apparent increase in size of field defect.

Cyclotonia leads to spasm of accommodation, transient myopia and frontal headache. Delayed effect consist of epiphora due to spasm of puncta and canaliculi. Cholinergic effect of pilocarpine on lacrimal gland enhances tear production.

In myopic eyes strong miotics are known to produce retinal detachment and subscapular opacification of lens. Prolonged use of pilocarpine may produce iris border cysts, which can be prevented by use of short acting mydriatic like phenylepherine from time to time.

Abnormal tear film status is a common feature of prolonged use of pilocarpine. Increased salivation, colic and diarrhoea are some systemic effects.

Other miotics are not used in children to treat glaucoma.

B. Sympathomimetic drugs (adrenergic agonist). There are two types of drugs in this group. The drugs that stimulate both alpha and beta receptors are known as non selective alpha agonist. Those drugs that stimulate only alpha two receptors are called selective alpha agonist. These drugs increase outflow facility and to some extent reduce formation of aqueous.

I. Epinephrine. Epinephrine is used as aqueous drop, commonly used strength is 1% to 2% given either once a day or at the most two times a day. The salts of epinephrine available are hydrochloride, bitarterate and borate. Out of all salts the borate is least irritating due to its pH 7.4, which is nearer to pH of normal tear.

Epinephrine directly stimulates both alpha and beta receptors. The IOP lowering mechanism of epinephrine is most probably a dual one, the first an early but short period of decreased aqueous formation and the later a long period of increased outflow. The increased outflow has an early and late phase. The early phase of increased outflow starts within few minutes but the late phase takes weeks to months fully to operate.103, 107

Untowards effect of epinephrine consists of :

1.Tachyphylaxis is common as epinephrine.

2.Besides lowering intraocular pressure, epinephrine causes - constriction of conjunctival vessels leading to blanching of conjunctiva. This is short lived, followed by rebound hyperemia.

3.Mydriasis with epinephrine is prompt without cycloplegia.The mydriasis produced by epinephrine, is not counter acted by any drug in therapeutic dose. Hence epinephrine is contra indicated in narrow angled eyes.

4.Lid retraction. Due to stimulation of Muller’s muscle, there is always some lid retraction.

5.Prolonged use of epinephrine causes :

(a) Cystoid macular edema specially in aphakic and pseudophakic eyes. (b) Allergic blepharo conjunctivitis.

(c) Pigmentation of conjunctiva.

6. The systemic side effects consist of : Tachycardia, cardiac arrhythmia and hypertension.

Epinephrine is not a suitable drug for children.

II. Dipiveprin. This is synthetic epinephrine substitute. It is a pro drug i.e. it undergoes bio-transformation before exhibiting pharmacological action104, 105, 106. The compound is hydrolyzed to epinephrine after absorption in the eye. It is more lypophilic than epinephrine making its corneal penetration many times more than epinephrine. Its action is similar to epinephrine. It is used as 0.1% solution two times a day, its mydriasis is more than epimephrine. It does not stain contact lenses, maculopathy is less common. Additions of betablockers have an additive effect. It can be used in children. Its role in buphthalmos is uncertain.

Selective alpha agonist. These drugs selectively stimulate alpha two receptors. They reduce intraocular tension in two ways i.e. reducing aqueous formation and increasing uveoscleral outflow.

The two commonly available drugs are Apraclonidine and Brimonidine. Apraclonidine is a selective alpha two agonist. It is a derivative of clonidine107, 108, which is no more used in management of glaucoma due to its untoward side effects. Apraclonidine has prompt IOP reducing property when used as one percent solution. This property has been utilized to reduce sudden rise of tension following anterior segment laser procedures for glaucoma. It is used as 0.5% drops two times a day for management of glaucoma. It crosses the blood brain barrier minimally so its systemic side effects are very low and has no cardiopulmonary contra indication. Minor systemic side effects consists of dry nose and dry mouth. Commonest ocular side effect is chronic follicular conjunctivitis. Other ocular side effects consists of unwanted mydriasis, lid retraction and conjunctival blanching.

Brimonidine. It is selective alpha two agonist that reduces production of aqueous and increases uveoscleral outflow. It is used as 0.2% drop once or twice a day. It has minimal systemic side effect.

Betablockers. Betablockers are a group of drug that antagonise the adrenergic beta receptors. They are effective locally as well as when used orally or parentally. Locally, they are used only as drops. The local drops have systemic side effects as well. In fact betablockers when used for cardiological disorders were found to lower the intraocular pressure as well.

The betablockers are most widely used local drops for glaucoma therapy. They have replaced pilocarpine as first drug of choice. Their main function is to reduce aqueous production. The other modes of action are minimal lowering of episcleral pressure and slight increase in uveascleral outflow106, 107. They do not have any effect on pupil size or ciliary tone.

According to their cardio pulmonary action, they have been divided into two groups i.e. 1. nonselective that block both B1 as well as B2 adrenergic receptors and 2. cardio-selective that have no or very mild cardiac action.

Both types of betablockers have good additive effect when used with miotic. Commonly used non-selective betablockers are :

—Timolol 0.25%-0.5%

—Levobunotol 0.5%

—Cartelol 1%-2%

—Metiprantol 0.1%-0.3%

0.5% Betaxolol is the only cardio selective betablockers presently available.

Action of betablockers starts within 30 minutes and reach peak effect in 2 hours. The effect last for twelve to twenty hours. Hence they are administered twice a day. Initial fall of I.O.P with B.D. dosage is very good which becomes less in few weeks. This is called short term escape. Reduction in efficacy over months is called long term drift. Betablockers are effective in all types of glaucoma irrespective of width of angle. They have very little local side effects. Some eyes may experience ocular surface disorder. Other minor ocular side effects are burning, diminished corneal sensation and punctate erosion of cornea. The systemic side effects are bradycardia, reduced cardiac output, arrhythmia, heart failure and syncope. It causes bronchospasm, depression, anxiety and confusion.

The side effects can be minimised by using smallest possible drop and obstructing the lower puncta by pressing it with thumb for a minute following instillation in the conjunctiva.

In children it should always be used in consultation with pediatrician.

(d) Prostaglandin analogues. Prostaglandins are locally acting hormones scattered in various forms in various organs of the body. They are potent ocular hypotensive agents in very low dose. For ocular use they are available as latanoprost 0.005% drop in form of buffered isotonic solution with pH 6.7 and as unoprostane.

The latanoprost is used once in twenty four hours preferably at night as it reduces the nocturnal variation better than diurnal variation.

Latanoprost have synergistic effect with all anti-glaucoma drugs except pilocarpine. Latanoprost and pilocarpine both are known to reactivate uveitis and they are contra indicated in glaucoma secondary to uveitis.

Latanoprost is absorbed through cornea. It is an isopropyl pro drug that is hydrolysed by esterase in cornea to biologically active acid latanoprost. Peak concentration in aqueous is reached in two hours.

Its mode of action is by increasing uveoscleral outflow by 100% that reduces IOP by 35%. It is hundred times more potent than timolol 0.5%, has hardly any systemic side effects however hypersensitivity to latanoprost may occur.

Local side effects consists of reactivation of dormant anterior uveitis, worsening of existing iridocyclitis. Hence it is contra indicated in uveitis induced glaucoma. It also causes cystoid macular edema, less serious complications are darkening, thickening and elongation of lashes, darkening of skin of the lids.

E. Prostamides. These are chemical substances present in the eye like prostaglandin and histamine. They are neither hormones nor enzymes. They are members of fatty acidamide family. Prostamides are potent ocular hypotensive agents. They are believed to be involved in the endogenous regulation of IOP via prostamide sensitive receptors in the eye. Commonest form of prostamide used in bimotoprost that is a structural analogue of prostamide. It is used in once a day or twice a day dosage.

Carbonic anhydrase inhibitors (local as well as systemic). Oral carbonic anhydrase inhibitors are being used to reduce intraocular tension for last half a century109,111,112. Local use of carbonic anhydrase inhibitors (CAI) is a recent development and has not yet become

very popular. Advantages of CAI oral or local as ocular hypotensive agent lies in its versatility to lower IOP in all types of glaucomas, in all ages, irrespective of width of angle, pupillary size and duration.

Carbonic anhydrase is an enzyme widely distributed throughout the body that is responsible for the catalytic hydration of CO2 and dehydration of H2CO3. In the eye it is mainly concentrated in the ciliary epithelium where it is an integral part of aqueous formation by maintaining pH at optimum level.

Carbonic anhydrase inhibitors are a group of drugs that block the enzyme carbonic anhydrase and reduce formation of aqueous. By nature they are sulphonamides. They reduce formation of aqueous by twenty to twenty five percent. Being a sulphonamide they causes systemic acidosis and depletes serum potassium.

Acetazolamide is a prototype of all CAI, it is the most widely used systemic ocular hypotensive agent, mostly orally and rarely as intravenous injection to reduce acutely elevated IOP especially during retinal surgery.

Action of acetazolamide starts within one to three hours, reaches its peak in four to six hours. The effect passes off in ten to twelve hours. In children it is given in a dose of 10-20 mg/kg/day in divided doses. Acetazolamide does not change the pupillary size, depth of anterior chamber, width of angle of anterior chamber or structure of trabecular meshwork. Though CAI are mild diuretics, hypotensive property is independent of diuresis. As ocular hypotensive agent it can be used with all local and systemic oculo hypotensive agents. Sustained release acetazolamide has a delayed onset and prolonged therapeutic effect with less untowards effects. Acetazolamide is not administered for more than seven to ten days due to its systemic toxicity. However low dosages of acetazolamide i.e. as low as one fourth of usual dose have been found to give good oculohypotensive effect without much toxicity on long term.

Other carbonic anhydrase inhibitors are : Diclorphenamide 50mg once or two time a day, Methazolamide 25mg-50 mg pm once or twice a day.

Carbonic anhydrase inhibitors have a long list of systemic toxicity. They consist of 1. Metabolic acidosis, 2. Paresthesia, 3. Fatigue, 4. Headache, 5. Nausea, 6. Diarrhoea, 7. Metallic taste, 8. Diuresis, 9. Renal stone formation, 10. Thrombocytopenia, 11. Mild to severe mucocutaneous involvement may lead to Stevens Johnson syndrome. Only ocular side effect is transient myopia.

Locally acting CAI. Action of local carbonic anhydrase is same as systemic CAI i.e. blocking the enzyme carbonic anhydrase at ciliary epithelium due to change in pH thus reducing production of aqueous. The drug is absorbed through cornea. Absorption depends upon its lipid and water solubility, contact time and strength. Commonly used local CAI inhibitors are dorzolamide 2% two times a day, brinzolamide 1% and acetazolamide 5% two times a day.

Local CAI are less effective in children than in adults.

Common side effects are local irritation, conjunctival congestion, metallic taste. Systemic side effects are rare with local drops.

Hyperosmotic agents. Hyperosmotic agents are a group of drugs that lower intra ocular pressure following oral or intravenous administration by reducing vitreous volume. These drugs create a fluid gradient between the vitreous and blood which pulls fluid from the vitreous.