Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009
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Fluorescein Sodium and Other Dyes |
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Exact mechanism of fluorescence is not known. Havener suggests that a break in the epithelial barrier permits penetration of fluorescence into the Bowman's layer and stroma. Dye makes contact with alkaline interstitial fluid from aqueous and this causes change in colour of flourescein.
2.Siedel's test- a drop of fluorescein is placed on the superior bulbar conjunctiva in an attempt to detect a surgical wound leakage after cataract extraction. If leak is present a bright green rivulet of aqueous flows through the flourescein on the cornea. It is best seen in cobalt blue light or cobalt blue filter of slit lamp.
3.Contact lens fitting and management. It detects corneal epithelial damage. In soft contact lens usage if limbal epithelial hypertrophy occurs it leads to pooling of fluorescein around limbus.
4.Lacrimal system evaluationit is used to evaluate the integrity of precorneal tear film and patency of lacrimal drainage system. Tear break up time is defined as the interval between the last complete blink and the development of first randomly distributed dry spot in the tear film. Tear break up time less than 10 seconds indicates unstable tear film. It is also used to evaluate epiphora. 2% solution is used for patency of lacrimal system.
5.It is used to record IOP by applanation tonometry. O.25% solution is used for this purpose.
Intravenous Fluorescein
Fluorescein is excreted by a wavelength of 465nm and emits a wavelength of 525 nm. In bloodstream it binds to albumin and redblood cells. 80% of Fluorescein in blood is bound to albumin and remaining is present in free form unbound to albumin which passes through blood ocular barriers when it is damaged. This property of Fluorescein is made to use of fluorescein, to outline the vasculature of retina and to delineate lesions within the layers.
Fluorescein is available as 5%,10% and 25% solution. Depending on the concentration, quantity needed differs, i.e. 10ml of 5%, 5ml of 10%, 3ml of 25%. 25% solution is used when media is more opaque.After injection through antecubital vein the dye reaches retinal circulation (central retinal artery) in 10 - 15 seconds. The passage of dye through the circulation is divided into various stages. There may be hyperfluorescence or hypofluorescence depending on the pathology.
Hyperfluorescence Occurs Due To
i)Window defect — due to RPE atrophy and resultant unmarking of choroidal fluorescence.
ii)Pooling of dye — in subretinal and sub RPE space.
iii)Leakage — abnormal vasculature.
iv)Staining — Drusen.
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Hypofluorescence Occurs Due To
i)Blockage of fluorescence by retinal or choroidal lesion.
ii)Filling defects due to vascular occlusion.
Uses
1)Delineate vascular abnormalities of fundus.
2)In occlusive carotid disease by comparing the arm to retina circulation of both sides. A difference of more than 1 second is significant.
3)Iris angiography - for visualization of iris tissues and vessel infarcts.
4)Aqueous flow assessment.
VITREOUS FLUOROPHOTOMETRY
It is a non-invasive method of measuring fluorescein in vitreous. This is used to study the integrity of bloodretinal barrier.
Fluorescein can also be administered orally as powder form(1-2 gm) mixed in fruit juices. The dye appears in fundus in 15 minutes.
Side Effects
i)Nausea and vomiting are the most common and it depends on concentration of dye.
ii)Allergic reaction like urticaria, pruritis or pulmonary edema.
iii)Cardiovascular toxicity like hypotension and shock.
iv)Pain at site of injection and paresthesia of tongue and lips.
v)Temporary discolouration of skin and veins.
vi)Topical preparations cause transient urticaria of cornea or conjunctiva. Since hypersensitivity may occur; emergency medication should be available. It may stain soft contact lens, therefore should be reinserted after 1-2 hours of fluorescein application.
FLUOREXON
Fluorexon is N, N - bis - aminomethyl fluorescein tetrasodium salt. It is pale, yellow brown in colour. It stains both epithelial defects and devitalized tissues. It is less absorbed by contact lens and is more useful in evaluating contact lens fit. It is also particularly useful in evaluating hybrid design contact lens.
Topical application may produce mild stinging sensation. It is not used with highly hydrated soft lens because of discoloration.
ROSE BENGAL
It is mostly used in diagnosis of ocular surface disease. It is a derivative of Fluorescein and stains only degenerated or dead cells and mucous strands. It is formulated as 1% solution, and available as sterile filter paper strips.
It is a photoreactive compound which reacts with light and oxygen to form singlet oxygen which causes damage to single stranded DNA and cell membranes. Therefore, it is not a vital dye.
Fluorescein Sodium and Other Dyes |
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Uses
i)Evaluation of corneal ulcer.
ii)Diagnosis of keratoconjunctivitis sicca. George et al developed a grading scale for quantifying the severity of dry eye.
Grade |
Description of severity |
Punctate spots |
|
|
|
0 |
Absent |
0 |
1 |
Minimal |
3-10 |
2 |
Mild |
11-30 |
3 |
Moderate |
31-80 |
4 |
Severe |
>80 |
|
|
|
Rose Bengal is used intravenously in animal studies, as it initiates photothrombosis. This is used in occluding the corneal new vessels.
Topical application causes stinging sensation which may be reduced by topical anaesthesia. The ability to stain is dose related, and it stains skin, and contact lenses. Intravenous administration may cause liver toxicity.
INDOCYANINE GREEN
ICG is a water soluble, tricarbocyanine dye with peak absorption in near infrared spectrum of 805nm and maximal emission at 835nm. On intravenous administration 98% of the dye is protein bound; it does not leak through choriocapillaris and gives outline of choroidal circulation.
Uses
1.Fluorescent dye for retinal and choroidal angiography. It is mostly used to identify ischemic, inflammatory and degenerative disorders. It is used most frequently to identify choroidal neovascularisation.
It is administered by dissolving the dye in an aqueous solvent at a concentration of 12.5mg/ml for a total dose of 50 mg. It is administered via the antecubital vein at a rate of 1ml/sec. A serial of images are taken by infrared scanning technique.
It is as safe as fluorescein. It may cause discoloration of skin, and mucous membrane. Since, it contains iodine it is not given to patients allergic to iodine.
Other less commonly used dyes are methylene blue (5 %) and lissamine green( 1%). Methylene blue stain devitalized cells, mucus and corneal nerves. It is used to stain lacrimal sac before DCR. Lissamine green is a vital stain which stains degenerated cells and mucus like Rose Bengal.
Botulinum Toxin
It is produced by bacteria clostridium botulinum. Botulinum A toxin serotype is used therapeutically. Botulinm selectively interferes with release of acetyl choline from nerve terminals. It causes dose dependent paralysis that lasts for 9 months.
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Clinical uses
i)Correction of strabismus.
ii)Nystagmus
iii)Blepharospasm
iv)Hemifacial spasm
v)Lower lid entropion.
In strabismus it is most effective in small angle deviation, transient sixth nerve palsy, overcorrection and residual deviation after squint surgery.
Adverse effects are diplopia, ptosis, hemorrhage, pupillary dilatation, reduced accommodation, local swelling, ecchymosis, dry eye, ectropion and ectropion after treatment of facial spasm.
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Irrigating Solutions
Irrigating solution refers to any aqueous solution that could be used to clean a tissue while maintaining its moisture. Both intraocular and extraocular solutions are available. Intraocular irrigating solution must supply nutrition to anterior segment particularly the sensitive corneal endothelium.
The irrigating solution should have desirable properties to prevent damage to ocular tissues. They should have appropriate osmolality, pH and required concentration of minerals, glucose. It also depends on the metabolic demands of the tissues it comes in contact with. Corneal epithelium obtains its nutrients from tear film and limbal vessels; therefore, extraocular solutions need not be exacting in nature. Corneal endothelium requires glucose for its nutrients and this is supplied by aqueous humor, therefore intraocular irrigating solutions should have glucose, calcium and magnesium which are required for cell adherens. Uvea, retina obtain their nutrition from ocular blood vessels and this is not dependent on irrigating solutions.
The irrigating solutions should have the required osmolality. All commercial ophthalmic solutions have about 300mosm. Hypertonic solution causes cell shrinkage due to water loss and a hypotonic solution causes edema and even destruction of cells.
Specific salts like calcium, magnesium should be added to maximize cell adhesions and cellular transport during surgery. An ideal pH of 7.4 is required. Preservatives are added for extraocular irrigating solutions for their antimicrobial effects.
Extraocular irrigating solutions which contains salt of sodium, potassium, magnesium, calcium with preservatives are used for
•First aid, in case of chemical injury.
•After tonometry for removal of fluorescein.
•After gonioscopy.
•After removal of foreign body.
•Diagnostic nasolacrimal duct irrigation.
•Washing out mucus, purulent discharge.
Intraocular irrigating solution like normal saline and Ringer lactate which were used earlier cause corneal edema after prolonged usage(more than 35 minutes).
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These cause early breakdown of corneal endothelial cells because these solutions lack calcium and magnesium.
Balanced salt solution(BSS) is significantly less traumatic. It contains calcium and magnesium salts. It is useful for short term intraocular surgery as corneal edema occurs on prolonged use as it contains only salts and no glucose and bicarbonate ions.
BSS plus contains glucose and bicarbonate ions. It contains Glutathione as a reducing agent which prevents damage to endothelial cells by oxidants. BSS contains citrate acetate buffer. BSS plus should be prepared fresh every time. If surgery is done on compromised corneal endothelium or surgery exceeds longer than 60 minutes a complete irrigating solution is needed.
Glucose fortification of solution is needed to prevent cataract formation when vitrectomy is performed on diabetic individuals.
Components |
Ringer lactate |
BSS |
BSS plus |
|
|
|
|
p H |
6.6 |
7.4 |
7.4 |
NaCl |
102 |
109.5 |
122.2 |
KCl |
4 |
10.1 |
5.1 |
CaCl |
3 |
4.3 |
1.1 |
MgCl |
|
1.5 |
1.00 |
Sodium phosphate |
|
|
2.8 |
Sodium bicarbonate |
|
|
25 |
Glucose |
|
|
51 |
Glutathione |
|
|
0.3 |
disulfate |
|
28.6 |
|
Sodium acetate |
|
5.8 |
|
Sodium citrate |
28 |
|
|
Sodium lactate |
|
|
|
Sodium gluconate |
|
|
|
|
|
|
|
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Vitreous Substitutes
The success of surgery for retinal detachment is dependant on attaining closure of a retinal break, relieving traction on the retina by thorough dissection of epiretinal membranes or scleral buckling, or both, and minimizing the recurrence of traction. The use of intravitreally injected gaseous and liquid materials as adjuvant agents to vitreoretinal surgery plays a vital role in facilitating retinal reattachment. These materials are used as
i)Intraoperative instruments to reestablish intraocular volume.
ii)Assist in separating membranes adherent to the retina.
iii)Manipulate the retinal detachment.
iv)Mechanically flatten detached retina.
v)In the long, intravitreal gases and silicone oil maintain the neural retina in apposition to retinal pigment epithelium post-operatively.
Intra Operative Use of Vitreous Substitute Material
During surgery, substances are injected into the vitreous cavity to maintain intraocular volume and they are also used for their mechanical properties to function as 'soft instruments'. These liquids assist in separation of membranes or in hypokinetic manipulation of the retina and are used in membrane dissection, such as delamination and retinotomy. Finally at the end of the procedures, a material of high surface tension is injected to maintain closure of the retinal break until the maturation of chorioretinal adhesion is attained. A variety of gaseous and liquid substances are currently used intraoperatively.
Air and Other Gases
Air was the first gas to be employed in retinal surgery. Air can be used intraoperatively during buckling surgery to restore intraocular volume after drainage of subretinal fluid, to flatten 'fish mouth tears' that form radial folds, and to unroll the posterior flap of large retinal tear. The tamponade lasts only for 2448 hours.
Viscoelastic Fluids
The Viscoelastic fluids used in vitreoretinal surgery include sodium hyaluronate, chondroitin sulfate or hydroxypropyl methyl cellulose which are having molecular weights ranging from 30,000 to 4 million Daltons. At zero shear
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rate (steady state) these materials exhibit high viscosity, whereas at high shear rates (shearing occurs when a fluid is made to flow) the polymers undergo temporary and reversible deformation (pseudoelastic behavior), with the result that the viscosity of material decreases. This behavior makes the material to be injected through the small gauge cannulas and yet it will regain its shape after injection.
Sodium hyaluronate is most favorable viscoelastic used in vitreoretinal surgery.
It can be used to
i)gently separate an embedded foreign body from the retinal surface or choroid.
ii)separation of epiretinal membranes found in proliferative diabetic retinopathy
iii)unfold the retina during repair of giant retinal tear and to manage hemorrhage
Low Viscosity Perflurocarbon Liquids
Perflurocarbon liquids have properties of high density, surface tension, low viscosity and are optically clear. They can be easily injected and aspirated through small - gauge microsurgical instruments. The specific gravity of perflurocarbon liquids is almost twice the density of water, hence the force exerted by perflurocarbon liquids against the retina is greater than of silicone oil and flurosilicone oil. The interfacial tension of perflurocarbon liquids with water is roughly equivalent to silicone oil, and the material tends to be cohesive, so that liquid remains in one large bubble. Perflurocarbon liquids have some deterrence to passage through a break and are virtually inert.
Eg. - perflurotributylamine
•perflurodecalin.
•Peflurophenanthrene.
•Perflurooethylcyclohexane.
•Perflurooctylbromide
•Perfluro - n- ocatane
Perfluro - n - ocatane is preferred because, it is highly purified, has relatively lower boiling point and higher vapor pressure than other perflurocarbon liquids.
Indications
•retinal detachment with severe proliferative vitreoretinopathy
•traumatic retinal detachment
•giant retinal tears
•management of sub retinal hemorrhage, vitreous hemorrhage, dislocated lens and intraocular lenses and retinal detachment secondary to macular hole.
•To locate the peripheral retinal breaks that were not seen preoperatively.
•Aid in the removal of foreign body
Vitreous Substitutes |
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Silicone Liquid
Silicone liquid injection needs high pressure because of its high viscosity, bimanual manipulation is needed because of its lower density than that of water. It has been used during pars plana vitrectomy
•To reposition the retina
•Removal of the epiretinal membrane
•Unroll the flaps of retinal tears.
Fluorosilicone has higher specific gravity than silicone oil and has been used as an alternative intraoperative tool in the management of inferior retinal detachment.
Intraocular Gas
Intraocular gases are mainly employed for pneumatic retinopexy and are used in conjunction with scleral buckling and drainage of sub retinal fluid. In addition, for complicated forms of retinal detachments requiring vitrectomy, such as proliferative vitreoretinopathy or giant retinal tears, gases are used to provide internal tamponade post operatively. Two properties of a gas bubble are of particular importance in the repair of retinal detachment.
i)High surface tension between the gas bubble and the thin layer of aqueous covering the retina serves to tamponade a retinal break by blocking the flow of fluid from the vitreous cavity.
ii)Specific gravity of air or any gas is lower than that of water, the gas bubble exerts a buoyant force that pushes the neural retina against the pigment epithelium.
The gases commonly used for intraocular use are
•Sulfur hexafluoride (SF6)
•Perfluromethane (CF4)
•Perfluroethane (C2F6)
•Perfluropropane(C3F8)
•Octafluorocyclobutane(C4F8)
•Perfluoro - n- butane(C4F10)
Sulfur hexafluoride reaches its maximal expanded volume by 24 to 48 hours after injection. Perfluropropane reaches its maximal expanded volume by 72 to 96 hours after injection. These expansile substances are avoided in eyes with preexisting glaucoma or synechial angle closure. Intraocular gases are more useful in superior retinal breaks, in cases of superior and inferior retinal breaks intraoperative gases are mixed with silicone oil for better apposition.
Hydrophilic polymers( hydrogel) are used experimentally for apposition of retinal breaks. They can be used for superior and inferior retinal breaks. They are optically clear and special positioning of the patients are not required. Drawbacks of hydrogels are, they may react with ocular tissue and they are difficult to inject.
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Complications
Silicone oil use can lead to cataract due to mechanical obstruction of diffusion of nutrients to the lens. Therefore the patient has to avoid prolonged supine position. It can lead to glaucoma ma in aphakic eyes by pupillary block and emulsification of silicone oil leads to trabecular meshwork obstruction. Pupillary block is avoided by doing inferior iridectomy. Silicone oil in the anterior chamber may cause decompensation of corneal endothelium.
Intraocular gases can lead to cataract, pupillary block glaucoma, and corneal decompensation. Excessive gas expansion may lead to central retinal artery occlusion. It can cause optical disturbances due to scattering of light.