Glaucoma Flashcards
Where and how is aqueous humour produced?
produced from plasma by the ciliary epithelium of the ciliary body pars plicata, using a combination of
active and passive secretion. A high protein filtrate passes out of
fenestrated capillaries (ultrafiltration) into the stroma of the ciliary
processes, from which active transport of solutes occurs across the
dual-layered ciliary epithelium. The osmotic gradient thereby established facilitates the passive flow of water into the posterior chamber.
What is the nervous control of aqueous humour production?
Secretion is subject to the influence of the sympathetic nervous system, with opposing actions mediated by beta-2
receptors (increased secretion) and alpha-2 receptors (decreased secretion). Enzymatic action is also critical – carbonic anhydrase is
among those playing a key role.
What are the 3 components of trabecular meshwork?
Uveal meshwork
Corneoscleral meshwork
Juxtacanalicular (cribiform) meshwork
What proportion of aqueous humour drains through the trabecular meshwork?
90%
What is the anatomy of Schlemm canal?
a circumferential channel within the
perilimbal sclera. The inner wall is lined by irregular spindle-shaped endothelial cells containing infoldings (giant vacuoles) that are thought to convey aqueous via the formation of
transcellular pores. The outer wall is lined by smooth flat cells and contains the openings of collector channels, which leave the canal at oblique angles and connect directly or indirectly with episcleral veins. Septa commonly divide the lumen into
2–4 channels.
What are the 3 pathways of outflow of aqueous?
Trabecular (90%)
Uveoscleral (10%)
Iris (minimal)
What is the mean IOP in general population?
16
What % of population >40 have IOP >21 with open angles and no detectable glaucoma damage?
4-7%
What is the OHTS study?
a multicentre longitudinal trial. In addition to looking at the effect of
treatment of individuals with ocular hypertension (IOP in one eye
between 24 mmHg and 32 mmHg), invaluable information was
gained about the effect of a range of putative risks for conversion
from OHT to glaucoma.
What are the limitations of OHTS study?
the study goal was an IOP reduction of 20%, which may not be sufficient in some individuals; compliance with medication was not measured;
and there is a possibility that early glaucomatous damage was
already present in some patients.
What are some conclusions based on factors significant on multivariate analysis from OHTS study?
○Intraocular pressure. The risk of developing glaucoma increases with increasing IOP.
○ Age. Older age is associated with greater risk.
○Central corneal thickness (CCT). The risk is greater in eyes with OHT and CCT <555 µm and lower in eyes with high CCT (>588 µm). This may be due to under- and overestimation of IOP, although it is more likely that associated structural factors, perhaps at the lamina cribrosa, might be
involved.
○Cup/disc (C/D) ratio. The greater the C/D ratio the higher the risk. This may be because an optic nerve head with a
large cup is structurally more vulnerable, or it may be that
early damage is already present.
○Pattern standard deviation (PSD). The higher the PSD value the greater the risk. (This possibly signifies early
glaucomatous field change.)
What are some conclusions based on factors that were significant on uni-
variate analysis only in OHTS study?
○African ethnic background (including Afro-Caribbean, African-American) is associated with a higher glaucoma
risk.
○Males are more likely to convert.
○Heart disease is a significant risk factor
What are some conclusions based on Factors examined in the OHTS but found to be insignificant?
○ Myopia (although it is suspected that myopic discs are more susceptible to glaucomatous damage at a lower IOP than emmetropic discs).
○Diabetes.
○Family history of glaucoma (which is curious, as patients with glaucoma often have a family history of the disease).
What are overall conclusions from OHTS study?
○Early treatment reduces the cumulative incidence of glaucoma.
○The effect is greatest in high-risk individuals.
○Early treatment of low risk individuals is not needed.
○Individualized assessment of risk is useful and helps to guide management.
What are some genetics of ocular hypertension?
A single nucleotide polymorphism in TMC01 appears to be significantly associated with conversion to glaucoma in white people with
ocular hypertension (3-fold risk in individuals with two risk alleles
compared with those with no risk alleles).
A recent meta-analysis
has identified 112 genetic loci associated with IOP and suggests a
major role for angiopoietin-receptor tyrosine kinase signalling,
lipid metabolism, mitochondrial function and developmental
processes as risk factors for elevated IOP.
What is pre-perimetric glaucoma?
This concept refers to glaucomatous damage, usually manifested by a suspicious optic disc and/or the presence of retinal nerve fibre
layer defects, in which no visual field abnormality has developed.
The field-testing modality for this purpose is usually taken as
standard achromatic automated perimetry.
What was the percentages in people treated for OHT in OHTS study?
9.5% cumulative risk for people to develop glaucoma with OHT
Reduced to 4.4% in patients which low IOP attained
What is the definition of glaucoma?
Glaucoma is the term that is used to describe a group of conditions that have in common a chronic progressive optic neuropathy
that results in characteristic morphological changes at the optic
nerve head and in the retinal nerve fibre layer. Progressive retinal
ganglion cell death and visual field loss are associated with these
changes. Intraocular pressure is a key modifiable factor.
What % of people does glaucoma affect above the age of 40?
2-3%
What does the Early Manifest Glaucoma Trial (EMGT) provide data on?
prospective natural history data on progression of glaucoma in three common glaucoma types: high tension glaucoma (HTG), normal-tension glaucoma (NTG) and pseudoexfoliation glaucoma (PXEG),
using visual fields as an end-point.
The study reveals that the
mean rate of change in untreated individuals is as follows: HTG
−1.31 dB/year, NTG −0.36 dB/year, PXEG −3.13 dB/year.
What is POAG characterized by?
*Retinal nerve fibre layer thinning.
*Glaucomatous optic nerve damage.
*Characteristic visual field loss as damage progresses.
*An open anterior chamber angle.
*Absence of signs of secondary glaucoma or a non-glaucomatous
cause for the optic neuropathy.
*IOP is a key modifiable risk factor.
Which ethnic groups is POAG most prevalent in
European/African
Risk factors for POAG?
1) High IOP. Asymmetry >4 significant
2) Older age
3) Difficult to control in black than white people
4) FH POAG- sibling 4x, offspring 2x risk
5) Myopia
6) Anti VEGF injections risk of IOP elevation. More with bevacizumab than ranibizumab
7) Contraceptive pill- blocks protective oestrogen effect
8) Vascular disease
9) Translaminar pressure gradient- difference in level of IOP and orbital CSF pressure increase likelihood and progression of glaucoma damage due to associated deformation of lamina cribrosa
10) Optic disc area- large discs more vulnerable to damage
11) Ocular perfusion pressure. Large difference between arterial BP and IOP increase risk and progression of glaucoma
Which gene is associated with POAG?
MYOC gene coding for myocillin protein in trabecular meshwork and OPTN gene coding for optineurin
What is the pathogenesis of glaucomatous optic neuropathy?
Retinal ganglion cell death through apoptosis rather than necrosis. Preterminal event is calcium ion influx into cell body and rise in intracellular nitric oxide.
After injury, astrocyte and glial cell proliferation and alteration in ECM of lamina cribrosa and optic nerve remodelling.
What are the proposed mechanisms of optic nerve damage in glaucoma?
1) Direct mechanical damage to retinal nerve fibres at ONH as they pass through lamina cribrosa
2) Ischaemic damage due to compression of blood vessels at ONH.
3) Both mechanisms lead to reduced axoplasmic flow
In history taking, what aspects of previous ophthalmic history may be relevant?
Refractive status- myopia increased risk of POAG, hypermetropia PACG
Causes of secondary glaucoma eg ocular trauma or inflammation. Previous eye surgery eg refractive surgery which can affect IOP readings
What are the 4 subtypes of glaucomatous damage?
Focal ischaemic discs: Localised superior and or inferior notching and associated with localised field defects with early threat to fixation
Myopic disc with glaucoma- tilted shallow disc with temporal crescent of PPA + glaucoma damage. Sense superior/inferior scotomas are common.
Sclerotic discs- shallow saucerized cups and gently sloping NRR, variable PPA + peripheral VF loss.
Concentrically enlarging discs- fairly uniform NRR thinning and diffuse field loss. IOP significantly elevated at presentation
