Open-angle glaucoma (OAG) is a chronic, progressive, and irreversible multifactorial optic neuropathy that is characterized by open angle of the anterior chamber, typical optic nerve head changes, progressive loss of peripheral vision (typical visual field changes) followed by central visual field loss (blindness) for which intraocular pressure (IOP) is an important risk factor. The disease is usually bilateral, but asymmetry is often seen.
The proposed definition for definite OAG by Rotterdam study is 'a glaucomatous optic neuropathy in eyes with open angles in the absence of history or signs of secondary glaucoma characterized by glaucomatous changes based on the 97.5 percentile for this population together with glaucomatous visual field loss. In the absence of the latter or of a visual field test, it is proposed to speak of probable OAG based on the 99.5th or possible OAG based on the 97.5th percentiles of glaucomatous disc changes for a population under study.
Open-angle glaucoma is characterized by partial blockage of the trabecular meshwork in the eye, though the drainage angle between the cornea and iris remains open. Due to this blockage, the pressure in the eye gradually (very slowly) increases, resulting in damage to the optic nerve (progressive visual loss).
The rapid deterioration of visual field in OAG is associated with the following baseline features: worst mean deviation, a greater vertical cup-to-disc ratio at baseline, or older age.
Glaucoma is the second leading cause of blindness globally, and in the USA. Glaucoma is the leading cause of blindness in blacks. Overall, open-angle glaucoma is more common in populations of European or African descent than in populations of Asian descent in whom angle-closure glaucoma is more common. There are at least 2.7 million people aged ≥40 years with glaucoma in the United States. In 2015, there were 57.5 million people worldwide with primary OAG, and in 2020 65.5 million people are expected to be affected.Bilateral blindness due to OAG has been estimated to affect 4.5 million people in 2010 and 5.9 million people in 2020.
The exact cause of neuropathy encountered in open-angle glaucoma is not well known, though multiple risk factors have been identified.
Elevated Intraocular pressure:
Of these risk factors, the most studied risk factor had been elevated IOP, as it is modifiable. It has been shown that once IOP rises above 21 mmHg, there is a significant increase in the risk of developing visual field loss (even with only small increases in IOP), especially once IOP rises above 26 mmHg to 30 mmHg. High IOP is an important risk factor for the progression of glaucoma. High fluctuation of IOP may also lead to glaucoma progression. Reduction of IOP leads to less progression or stabilization of the glaucomatous optic nerve changes and visual field changes. About 40-50% of all OAG cases have IOP below 22 mm Hg in a single screening.
Pathomechanism of glaucoma:
The two main proposed mechanisms by which an elevated IOP is thought to contribute to glaucomatous damage includes vascular dysfunction resulting in ischemia to the optic nerve, and mechanical dysfunction as a result of compression of the axons by the cribriform plate.
When open-angle glaucoma in a patient is attributed to elevated IOP, the cause of this increase in IOP is commonly thought occur due to dysfunction in aqueous outflow through the trabecular meshwork of the eye. This may occur as a result of partial obstruction due to foreign material (e.g., accumulated mucopolysaccharides, in the trabecular meshwork), a reduction in the number of trabecular endothelial cells, a decreased density of trabecular pores, number of vacuoles, or size of the inner wall endothelium of the canal of Schlemm, loss of phagocytic activity, or dysfunction in the neurological feedback loop involved in drainage of aqueous humor. It is important to note that unlike angle-closure glaucoma, the drainage angle between the iris and cornea remain open in open-angle glaucoma.
Other proposed mechanisms for obstruction of aqueous humor outflow include oxidative damage to the meshwork, abnormal corticosteroid metabolism, adrenergic dysfunction, or an immunological process.
Finally, it has been proposed that certain individuals may have a genetic predisposition to cell death of individual axons in the eye, resulting in the release of potentially cytotoxic substances such as glutamate, calcium, nitric oxide, and free radicals, as well as apoptosis of neighboring cells.
Early changes in vision due to open-angle glaucoma involves a loss of peripheral vision at first, while visual acuity (e.g., central vision) is maintained until late in the course of the disease. For this reason, open-angle glaucoma progresses relatively asymptomatically, and patients often do not present with symptoms or visual complaints until late in the course of the disease. Thus, it is a silent, but potentially blinding disease. History should include:
OAG is characterized by a typical triad of
However, for a diagnosis of OAG high IOP is not mandatory. The American Academy of Ophthalmology defines primary OAG as 'chronic, progressive optic neuropathy in adults in which there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. This condition is associated with an open anterior chamber angle by gonioscopy.'
If the patient has a history of progressively declining visual acuity, it is important to rule out other potential causes such as cataracts, ocular surface disorders (e.g., dry eyes or blepharitis), age-related macular degeneration, or medication-related side effects (e.g., cholinergic/miotics). Additionally, before forming a diagnosis of open-angle glaucoma, one must also consider other secondary causes of glaucoma such as pigment dispersion syndrome, steroid-induced glaucoma, intraocular tumors, exfoliation syndrome, ocular inflammatory disorders, elevated episcleral venous pressure, lens-induced glaucoma and other syndromes (e.g., Axenfeld-Rieger syndrome).
When examining the anterior segment of the eye via slit-lamp examination, the practitioner should also examine the following for any damage, defects or irregularities that may or may not be related to glaucomatous disease:
When determining the IOP of a patient using tonometry, certain variables must be taken into consideration. Tonometry measurements can, for example, vary between examiners differing by approximately 10% per individual, which can translate to a difference in IOP measurement of 1 mmHg to 2 mmHg. An individual’s corneal thickness or diurnal variations of IOP (e.g., higher IOP in early morning hours or other time of the day, or variability in the time of day of maximal IOP between patients) can also have a tremendous effect on the accuracy of IOP measurements. For this reason, multiple measurements should be taken in any patient suspected of having an elevated IOP, while also correlating measurements with both optic nerve and visual field examinations. If there are previous tonometry measurements available, they should be reviewed and compared to those that are most recent. Also, the IOP may be different on the same time of the day on different days. Different instruments may capture different values of IOP.
If a difference of 3 mmHg or more is noted between the two eyes, there should be an increased suspicion for the presence of glaucoma. Physicians should expect approximately 10% variation between individual measurements, and thus should repeat measurements over at least two to three occasions before deciding on the plan for treatment. Goldmann applanation tonometry (GAT) is thought as the gold standard for measuring IOP but is affected by corneal thickness. Higher corneal thickness gives falsely high values of IOP whereas low corneal thickness leads to a falsely low measurement of IOP.
Evaluation of optic nerve:
The optic nerve should ideally be evaluated using a slit lamp and 90D or 78D lens so that the 3-dimensional features of the optic nerve is better appreciated. Normally, the inferior neuroretinal rim (NRR) is the thickest, followed by superior, nasal, and temporal NRR. This is called ISNT rule. In OAG, this rule is not followed, as superior and inferior NRR gets thinned in the disease. The optic cup should be determined by its contour and not its color.
Typical optic nerve head changes in OAG include:
To make a diagnosis of acquired glaucomatous visual field defect Hoddap–Parrish–Anderson criteria is used:
Static automated threshold perimetry is used with white stimulus on white background. Most studies used the Humphrey Field Analyzer, but other perimeters like Octopus have also been used successfully. SWAP (short-wavelength automated perimetry using blue stimulus on yellow background) and frequency doubling perimetry may pick up early visual field defects. The visual field must be reliable and field defects should be repeatable on at least 2 fields. The same machine, the same degree of field and protocol (eg, 24-2, 30-3, or 10-2) should be used to compare the fields to note for progression or stability. It has been estimated that at least 40%-50% ganglion cell loss is needed to reliably show visual field defects in threshold perimetry. Thus, structural changes of the optic nerve occur earlier than functional change (visual field loss) in OAG. This gives rise to the concept of Preperimetric glaucoma which has been defined as 'the presence of characteristic glaucomatous changes in the optic disc and increased vulnerability to damage in the retinal nerve fiber layer (RNFL), without the presence of visual field defects detectable with standard automated perimetry'.
Typical visual field changes in OAG include.
Gonioscopy should be performed to document the status of angle and to document that the angle is open, which is an important pre-requisite for diagnosing OAG.
Photographic documentation of the optic nerve head is done by color and red-free disc photo preferably stereo photos. Red-free images highlight area of RNFL defects.
Automated analysis and detection of deviation from normal of the optic nerve head and retinal nerve fiber layer may be performed using various technologies including
The goal of treatment of open-angle glaucoma is:
To achieve this goal, the concept of Target IOP was introduced. It is the upper limit of IOP, below which it is estimated that the visual field and the optic nerve head/RNFL parameters will not deteriorate, and the quality of life of the patient will not get compromised.
Debate exists over the optimal time to initiate treatment of Open-angle glaucoma with some physicians initiating treatment of IOP once it reaches above only 21 mmHg, and others reserving treatment either until there is evidence of optic nerve damage or if the patient is at high risk of damage or progression of open-angle glaucoma.
Treatment should be initiated if signs of damage as a result of open-angle glaucoma are evident (e.g., disc hemorrhage, nerve fiber layer defects, asymmetric cupping, vertical ovalization or notching of the cup) or if symptoms of elevated IOP are present (e.g., halos, blurred vision, pain, IOP consistently above 28 mmHg to 30mmHg) due to the high risk of optic nerve damage in the setting of elevated IOP. Some physicians begin a monocular trial with medications only in one eye, to assess the effectiveness and side effects of chosen medications before treating both eyes. However, different eyes might have a different response to the same drug, asymmetric IOP fluctuation may occur, and the drug may have a contralateral effect.
A target IOP should be set individually depending on the severity of structural and functional damage, baseline IOP, age, race, family history, corneal thickness, corneal hysteresis, and other risk factors.
Follow-up should also be scheduled based on the level of success in IOP reduction between visits (e.g., more frequent follow-up with slower progression in treatment response) and the severity of optic nerve damage/visual field loss.
Overall, treatment should be individualized, taking into consideration the risk factors, systemic complications of medication use, the patient’s life expectancy, medical history, concomitant conditions, and the patient’s desire to receive treatment. The target IOP should be revised based on the behavior of optic nerve head damage and visual function (visual field).
If IOP/visual field/optic nerve head worsens while the patient is on medical therapy the compliance to therapy must be checked. Also, systemic factors including diabetes, smoking, and nocturnal hypotension should be controlled. The physician should himself/herself confirm from the patient the drops and how many times the patient is using these. A check should also be done to note if the administration of topical drops is correct or not. Closure of eyelids after administration of drops with nasolacrimal duct occlusion may prevent systemic absorption of the topical medication.
Prostaglandin analog- Reduces IOP by 25% -33%. The usual dose in once daily. Side effects include lengthening of eyelashes, pigmentation of lids/ iris, exacerbation of uveitis/herpetic infection, and cystoid macular edema. It is preferred as initial therapy.
Adrenergic agents: Reduces IOP by 20%-25%. Brimonidine may cause allergic blepharoconjunctivitis and apnea/lethargy/bradycardia in children.
Beta-blockers: Reduces IOP by 20%-25%. Non-selective beta-blockers should be avoided in chronic obstructive pulmonary disease and asthma. Other contraindications include heart block, hypotension, and bradycardia.
Carbonic anhydrase inhibitor: Reduces IOP by 15%-20%.
Cholinergic/parasympathomimetic agents: Reduces IOP by 20%-25%.
These are used in the acute rise of IOP or when topical medications are not tolerated.
Carbonic anhydrase inhibitor:
Laser therapy for OAG:
The indications of laser trabeculoplasty include
The available methods of laser trabeculoplasty are:
Diode laser cyclophotocoagulation (DLCP)
DLCP is a method for ablation of the ciliary processes which secrete aqueous. Indications for DLCP include:
Surgical Management of OAG:
Indications for surgical management of glaucoma are
Surgical options include
This is another method of cycloablation using cryotherapy usually reserved for painfully blind eyes.
Painful blind eyes from glaucoma may need
The Americal Academy of Ophthalmology (AAO) preferred practice pattern (PPP) classifies the severity of glaucomatous damage to different categories:
'Mild: definite optic disc or RNFL abnormalities consistent with glaucoma as detailed above and a normal visual field as tested with standard automated perimetry (SAP)
Moderate: definite optic disc or RNFL abnormalities consistent with glaucoma as detailed above, and visual field abnormalities in one hemifield that are not within 5 degrees of fixation as tested with SAP
Severe: definite optic disc or RNFL abnormalities consistent with glaucoma as detailed above, and visual field abnormalities in both hemifields and/or loss within 5 degrees of fixation in at least one hemifield as tested with SAP
Indeterminate: definite optic disc or RNFL abnormalities consistent with glaucoma as detailed above, inability of patient to perform visual field testing, unreliable/uninterpretable visual field test results, or visual fields not performed yet'
Advanced POAG may cause optic atrophy and no perception of light, though most OAG patients will not lose vision in their lifetime. Risk factors for progression of OAG include:
In 10 years, the cumulative probability of end-stage glaucoma in at least one eye in untreated cases was 35% in a study.
Complications of glaucoma include:
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