Introduction to Drugs Used to Aid Diagnosis in Ophthalmology
The use of diagnostic dyes represents one of the most efficient, objective, non-invasive, and directly visible means we have of identifying and tracking ocular-surface changes at the cellular level. Though they’re particularly useful in dry-eye diagnosis and clinical trials, the utility of these dyes also extends far beyond dry eye to numerous other ocular surface conditions that affect corneal and conjunctival cells.
These dyes are:
The dye was first synthesized in 1871 by Adolf von Baeyer, Commonly referred to as fluorescein. The dye is used for fluorescein angiography and staining tear film, conjunctiva and cornea. It is fluorescein sodium (C20 H10 Na2 O5). It is the water-soluble salt of fluorescein, also known as resorcinolphthalein sodium, or Uranine, A member of the xanthene group of dyes. It is a highly fluorescent chemical compound synthesized from the petroleum derivatives resorcinol and phthalic anhydride.
Fluorescence (Mechanism of action)
Fluorescein is a synthetic organic compound available as a dark orange/red powder soluble in water and alcohol. Fluorescence is a type of photoluminescence that occurs when susceptible molecules known as fluorophores absorb electromagnetic energy, temporarily exciting them to a higher energy state. As the molecules return to their original energy level, they emit light of a different, usually longer wavelength.
Unlike phosphorescence, which continues to occur after the excitation source is removed, fluorescence requires continuous excitation. Once the excitation source is removed, emission of fluorescence stops almost immediately (10-8 seconds)
Fluorescence occurs naturally in certain compounds and may occasionally be observed in the human eye.
Fluorescein absorbs blue light, with peak excitation occurring at wavelengths between 465-490 nm. The resulting fluorescence occurs at the yellow-green wavelengths of 520 to 530 nm. Dye concentration and pH can affect the intensity of fluorescence. Maximum fluorescence occurs at a pH of 7.4
Fluorescence is detectable in concentrations between 0.1% and 0.0000001%. In broad-spectrum illumination, diluted fluorescein sodium appears bright yellow-green in color. When illuminated with blue light, the yellow-green color intensifies.
The fluorescent properties of this dye have made it useful in a variety of industrial, scientific, military, and medical applications
It was first fluorescent dye used for water tracing purposes.
It has been used as a visible marker for search-and-rescue operations, to track and measure flow dynamics of water sources, map subterranean water courses, track hazardous spill dispersion patterns, identify point sources of pollution, and to detect leaks or obstructions in plumbing and sewage systems.
In ophthalmology, topical application of fluorescein sodium is routinely used for:-
Fluorescein strips are used in 2% and 4% concentration
As a vital stain in the documentation of ocular surface disorders such as corneal ulcers, abrasions, or other epithelial defects
Determine tear film breakup time
Check the fit of contact lenses
Patency of lacrimal passageways
To detect leakage of aqueous humour from corneal or conjunctival wounds using the Seidel Test.
Three and nine o’clock staining- present parallel to the nasal and temporal limbus and is due to contact lens associated dry eye. Patients may experience mild discomfort.
Dimple veil staining- is not true staining, but rather pooling of the dye into corneal indentions caused by trapped air bubbles under a poorly fitting rigid gas permeable contact lens. It presents as sharply demarcated, circular patterns of stain on the cornea.
Uses in Medicine
It has been used for intra-operative assessment of blood flow in surgical resections and grafts with a Wood’s Light to excite fluorescence.
The most common uses of fluorescein angiography are in retinal or choroidal vascular diseases such as Diabetic Retinopathy
Age-related Macular Degeneration
Photographic surveillance of passage of fluorescein through retinal and choroidal circulation
A molecule is excited by light of the certain wavelength to a higher energy level, release photon then comes down to the original state
Dosage and Administration
Fluorescein angiography is performed by injecting fluorescein sodium dye as a bolus into a peripheral vein. The normal adult dosage is 500mg and is typically packaged in doses of 5 ml of 10% or 2 ml of 25%. For pediatric patients, the dose is adjusted to 35 mg per 10 pounds of body weight. Upon entering the circulation, approximately 80% of the dye molecules bind to plasma proteins. The remaining unbound or free fluorescein molecules fluoresce when excited with light of the appropriate wavelength. With a molecular weight of 376, fluorescein diffuses freely out of all capillaries except those of the central nervous system, including the retina.
The dye is metabolized by the kidneys and is eliminated through the urine within 24 to 36 hours of administration.
Side effects of intravenous fluorescein include discolouration of the urine for 24 to 36 hours and a slight yellow skin discolouration that fades within a few hours.
Nursing mothers should be cautioned that fluorescein is also excreted in human milk.
Use of fluorescein sodium may be contraindicated in patients with a history of hypersensitivity to fluorescein
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