Non-arteritic anterior ischemic optic neuropathy | |
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Other names | NAION |
Specialty | Ophthalmology |
Symptoms | Optic disc swelling, optic atrophy, vision loss |
Non-arteritic anterior ischemic optic neuropathy (NAION) is a medical condition characterized by loss of vision caused by damage to the optic nerve as a result of ischemia, or insufficient blood supply. The key symptom of NAION is optic disc swelling, which typically resolves within 2 months, but often leads to optic atrophy. The likelihood of vision improvement after developing this condition is low.
NAION is characterized by localized disruptions in blood flow to the optic nerve, often linked with broader systemic vascular conditions. Key risk factors include sleep apnea, diabetes, and hypertension. Currently, there is no universally accepted, scientifically proven treatment for NAION. However, there is a general consensus on the importance of managing underlying risk factors to prevent further complications. This includes controlling blood pressure, managing diabetes, and treating sleep apnea. [1]
The underlying causes of NAION are largely unknown. Multiple theories suggest different mechanisms for the reduction in blood flow that triggers this condition, but there is no consensus on the precise cause of optic nerve damage.
The term "disc-at-risk" refers to an optic nerve head characterized by a small cup-to-disc ratio and a crowding of optic nerve fibers. This anatomical feature is a significant factor in the development of NAION. [2] [3] Individuals predisposed to this condition typically have smaller optic discs with minimal or no cupping. This anatomical configuration leads to a congestion of nerve fibers, which can contribute to the onset of NAION. This mechanism is somewhat similar to compartment syndrome, where increased pressure within a confined space impairs blood flow and tissue function. [4]
The optic nerve head, or prelaminar disc, primarily receives blood from the peripapillary choroidal arterioles, which stem from the elliptical anastomotic annulus connected to the circle of Zinn-Haller. The circle of Zinn-Haller is formed by branches of the lateral and posterior ciliary arteries. [5] [6] Beyond this region, different segments of the optic nerve are supplied by various networks of arteries and capillaries originating from the ophthalmic artery and the central retinal artery. The Zinn-Haller circle also provides blood to the thin, sieve-like section of the eye's outer layer and the optic nerve fibers within it through small, inward-facing arteries. The area just behind this layer in the optic nerve is vascularized by small returning arteries and minute blood vessels that arise from the eye's surrounding circulation and the main ophthalmic artery, interweaving through the nerve's supporting fibers.
The parts of the optic nerve located within the eye socket and the canal it traverses receive blood from small arteries branching off the primary network surrounding the eye, as well as from the central retinal artery. Fluorescein angiographic studies [7] [8] have demonstrated that during the acute phase of NAION, there is a delay in blood flow to the optic disc, suggesting a potential impairment in the arteries directly supplying it. Other research indicates that a drop in blood pressure within specific critical areas of the optic disc's blood supply network may increase its susceptibility to damage. [9]
There are debates over other potential causes such as nighttime drops in blood pressure, as well as the hypothesis that the optic disc's ability to regulate its blood flow may be compromised. [10] Some researchers have even suggested that blockages in the veins could be responsible. [11]
One hypothesis suggests that the underlying cause may be a subtle decrease in blood flow to the optic nerve, which is enough to cause swelling of the nerve fibers but not severe enough to disrupt vision through tissue death and permanent damage to the optic nerve. When considering the possible causes for spontaneous NAION, the list includes other conditions like arteritic anterior ischemic optic neuropathy (associated with inflammation of arteries), optic neuritis (inflammation of the optic nerve), infiltrative and compressive types of optic neuropathy (where the optic nerve is invaded or pressed upon by abnormal substances or structures), diabetic papillopathy (swelling of the optic disc in diabetes), radiation-induced damage to the optic nerve, neuroretinitis (inflammation of the optic nerve and retina), and swelling of the optic disc linked with retinal diseases like central retinal vein occlusion.
While most cases of NAION have no known cause, it has been frequently linked to certain conditions. These include general surgical procedures, cataract surgery, hemorrhagic shock, certain medications, and optic disc drusen. The exact mechanism of optic nerve ischemia in these cases remains unclear, but contributing factors may include hypotension, anemia, hypoxia, and changes in the autoregulation of optic nerve arterial blood flow. The incidence of ischemic optic neuropathy leading to vision loss following general surgeries ranges between 0.1% and 0.002%. [13] [14]
Certain medications, such as amiodarone [15] and phosphodiesterase type 5 (PDE5) inhibitors like sildenafil, [16] [17] have been associated with optic neuropathy symptoms, including optic disc swelling and hemorrhages. The relationship between these medications and vision loss remains disputed due to anecdotal evidence, the lack of clear dose-response relationship, and co-existing risk factors. Clinical studies suggest a temporal increase in AION risk following PDE5 inhibitor use, leading to recommendations against their use in affected individuals to preserve remaining vision.
NAION in patients with optic disc drusen has unique characteristics: earlier onset, history of transient visual disturbances, and generally better visual outcomes. Mechanical pressure from drusen on blood vessels near the optic nerve may contribute to NAION development in these individuals. [18] [19]
Sleep apnea is a condition characterized by repeated interruptions in breathing during sleep, significantly affecting the flow of blood through the brain's blood vessels. These interruptions cause intermittent hypoxia, leading to vascular changes such as the constriction of cerebral blood vessels, thereby impacting overall brain blood flow. Sleep apnea can also result in reduced blood flow in the ciliary artery area, contributing to the development of NAION through various mechanisms.
The results of a retrospective study investigating high altitude (7,000-9,000 feet) as a potential risk factor for NAION suggested that high-altitude-associated NAION might be linked to undiagnosed obstructive sleep apnea. The study concluded that NAION could occur under high-altitude conditions, often in younger individuals with obstructive sleep apnea and "disc-at-risk". [20]
Each apnea episode typically causes temporary increases in blood pressure and heart rate, leading to fluctuations that can result in irregular blood flow to the brain. This may cause long-term changes in the structure and function of cerebral blood vessels. The brain's mechanism for maintaining constant blood flow despite changes in systemic blood pressure, known as cerebral autoregulation, can be impaired by sleep apnea. This impairment results in periods of both reduced and excessive cerebral blood flow. [21] [22]
Repeated airway obstruction during sleep leads to intermittent hypoxia, causing oxidative stress and damaging endothelial cells of blood vessels, including those supplying the optic nerve head. Chronic intermittent hypoxia impairs endothelial function, reducing nitric oxide production, which leads to vasoconstriction and reduced blood flow to the optic nerve head. Additionally, fluctuations in pressure within the thoracic cavity during apnea episodes can alter intraocular pressure, affecting the blood supply to the optic nerve head . Sleep apnea often causes dips in blood pressure during sleep, particularly in the early morning hours, reducing blood supply to the optic nerve head and increasing the risk of ischemia. [23] [24]
NAION is the most frequently diagnosed sudden optic nerve disease in adults over 50, predominantly affecting Caucasians, [25] with variable rates reported in Asian populations. [26] [27] While the exact number of cases is unclear, estimates suggest thousands of new cases occur annually in the United States alone. [28] [29] Associations with other health issues like diabetes and sleep apnea have been observed, though links with arteriosclerosis and cerebrovascular diseases are not typically found with NAION. [30] [31] [32] [33] [34] [35] [36] This condition affects both men and women equally, with the average age of onset being 66 years. [37]
NAION usually presents suddenly as painless vision loss in one eye, often noticed upon waking up. The visual field defects can vary, and while some patients may experience immediate maximal vision loss, others may notice a gradual worsening. The optic disc in these cases can appear swollen, sometimes accompanied by hemorrhages. [38] In some cases, there might be a phase where the disc appears swollen without immediate vision loss, potentially indicating a precursor to more severe damage. [39]
NAION may present with color vision deficiency and a relative afferent pupillary defect. In NAION, the severity of color vision deficiency correlates with the level of loss of visual acuity. [40]
Optical coherence tomography angiography effectively illustrates disruptions in microvascular blood flow within the retinal peripapillary capillaries and peripapillary choriocapillaries in individuals diagnosed with NAION. [41] [42] [43] [44] [45] This method aids in visualizing minute vascular changes that are crucial for accurate diagnosis. Concurrently, magnetic resonance imaging (MRI) of the optic nerves plays a pivotal role in distinguishing NAION from optic neuritis, a condition with similar symptoms. Notably, MRI revealed optic nerve abnormalities in only a small fraction (15.6%) of NAION patients, compared to almost all (96.9%) patients with optic neuritis. Additionally, certain symptoms, including elevated swelling, paleness, narrower arteries, and hemorrhages, were more common in NAION than in optic neuritis. [46]
The natural progression of NAION following acute vision loss typically includes an improvement in visual acuity by 3 or more lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart in 43% of those not receiving treatment. [47] As the initial swelling of the optic disc subsides, optic atrophy generally develops within one to two months after onset. A retrospective diagnosis of optic atrophy due to previous ischemic optic neuropathy is often possible when a small optic disc is detected in both the affected and the opposite eye, and when other tests for potential causes of optic atrophy yield normal results.
Following the ischemic damage to one optic disc, there exists a notable risk of involvement of the second eye. The recurrence rate of NAION in the same eye is approximately 6.4%. [48] Data from the trial estimate this risk at about 15% over 5 years. In cases where the second eye also experiences NAION, there is no clear consensus regarding the correlation between the final visual outcomes. [49] [50]
Proposed treatments include hyperbaric oxygen, [51] levodopa or carbidopa, [52] aspirin, [53] transvitreal optic neurotomy, [54] bevacizumab [55] [56] and vitrectomy. The Ischemic Optic Neuropathy Decompression Trial [57] [58] observed that while spontaneous visual function deterioration occurred in 12% of 125 control eyes, the condition worsened in 24% of 119 eyes that underwent decompressive surgery. [59] The application of corticosteroids in NAION treatment remains a topic of debate. [60] [61]
Research into potential therapies for NAION is ongoing, including studies using animal models to explore neuroprotective treatments for the optic nerve. Despite these efforts, including a clinical trial examining the potential neuroprotective effects of topical brimonidine that was discontinued due to stringent eligibility requirements, effective treatment for idiopathic NAION remains elusive. Further trials have been halted prematurely, and a third trial investigated the intravitreal injection of a small interfering ribonucleic acid targeting caspase 2 as a treatment approach.
Epigenetic reprogramming through a novel gene therapy shows promise in restoring vision loss in a non-human primate model of NAION. This study builds on previous research demonstrating that AAV2-induced transient expression of the reprogramming genes Oct4, Sox2, and Klf4 (OSK) could reverse retinal aging and restore visual function in mice. Given the limitations of mice for modeling human vision, African green monkeys were used as a more accurate model. NAION was induced in these primates, and two groups were treated with either AAV2-OSK gene therapy or a vehicle. The results showed that pre-treated eyes with AAV2-OSK had significantly improved visual function compared to vehicle-treated eyes, as measured by parameters such as pERG response and optic nerve axon count. Post-treatment also resulted in significant recovery, albeit after an initial decline. These findings suggest that AAV2-OSK gene therapy has potential for clinical application in treating human optic nerve diseases. [62]
Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes.
In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived from optic stalks during the seventh week of development and is composed of retinal ganglion cell axons and glial cells; it extends from the optic disc to the optic chiasma and continues as the optic tract to the lateral geniculate nucleus, pretectal nuclei, and superior colliculus.
Papilledema or papilloedema is optic disc swelling that is caused by increased intracranial pressure due to any cause. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare.
Amaurosis fugax is a painless temporary loss of vision in one or both eyes.
The optic disc or optic nerve head is the point of exit for ganglion cell axons leaving the eye. Because there are no rods or cones overlying the optic disc, it corresponds to a small blind spot in each eye.
Anterior ischemic optic neuropathy (AION) is a medical condition involving loss of vision caused by damage to the optic nerve as a result of insufficient blood supply (ischemia). This form of ischemic optic neuropathy is generally categorized as two types: arteritic AION, in which the loss of vision is the result of an inflammatory disease of arteries in the head called temporal arteritis, and non-arteritic AION, which is due to non-inflammatory disease of small blood vessels.
Posterior ischemic optic neuropathy (PION) is a medical condition characterized by damage to the retrobulbar portion of the optic nerve due to inadequate blood flow (ischemia) to the optic nerve. Despite the term posterior, this form of damage to the eye's optic nerve due to poor blood flow also includes cases where the cause of inadequate blood flow to the nerve is anterior, as the condition describes a particular mechanism of visual loss as much as the location of damage in the optic nerve. In contrast, anterior ischemic optic neuropathy (AION) is distinguished from PION by the fact that AION occurs spontaneously and on one side in affected individuals with predisposing anatomic or cardiovascular risk factors.
The ophthalmic artery (OA) is an artery of the head. It is the first branch of the internal carotid artery distal to the cavernous sinus. Branches of the ophthalmic artery supply all the structures in the orbit around the eye, as well as some structures in the nose, face, and meninges. Occlusion of the ophthalmic artery or its branches can produce sight-threatening conditions.
Ischemic optic neuropathy (ION) is the loss of structure and function of a portion of the optic nerve due to obstruction of blood flow to the nerve. Ischemic forms of optic neuropathy are typically classified as either anterior ischemic optic neuropathy or posterior ischemic optic neuropathy according to the part of the optic nerve that is affected. People affected will often complain of a loss of visual acuity and a visual field, the latter of which is usually in the superior or inferior field.
Arteritic anterior ischemic optic neuropathy is the cause of vision loss that occurs in temporal arteritis. Temporal arteritis is an inflammatory disease of medium-sized blood vessels that happens especially with advancing age. AAION occurs in about 15-20 percent of patients with temporal arteritis. Damage to the blood vessels supplying the optic nerves leads to insufficient blood supply (ischemia) to the nerve and subsequent optic nerve fiber death. Most cases of AAION result in nearly complete vision loss first to one eye. If the temporal arteritis is left untreated, the fellow eye will likely suffer vision loss as well within 1–2 weeks. Arteritic AION falls under the general category of anterior ischemic optic neuropathy, which also includes non-arteritic AION. AION is considered an eye emergency, immediate treatment is essential to rescue remaining vision.
Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain.
Ocular ischemic syndrome is the constellation of ocular signs and symptoms secondary to severe, chronic arterial hypoperfusion to the eye. Amaurosis fugax is a form of acute vision loss caused by reduced blood flow to the eye; it may be a warning sign of an impending stroke, as both stroke and retinal artery occlusion can be caused by thromboembolism due to atherosclerosis elsewhere in the body. Consequently, those with transient blurring of vision are advised to urgently seek medical attention for a thorough evaluation of the carotid artery. Anterior segment ischemic syndrome is a similar ischemic condition of anterior segment usually seen in post-surgical cases. Retinal artery occlusion leads to rapid death of retinal cells, thereby resulting in severe loss of vision.
Optic disc drusen (ODD) are globules of mucoproteins and mucopolysaccharides that progressively calcify in the optic disc. They are thought to be the remnants of the axonal transport system of degenerated retinal ganglion cells. ODD have also been referred to as congenitally elevated or anomalous discs, pseudopapilledema, pseudoneuritis, buried disc drusen, and disc hyaline bodies.
Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details.
Sohan Singh Hayreh was an ophthalmologist, clinical scientist, and professor emeritus of ophthalmology at the University of Iowa. As one of the pioneers in the field of fluorescein angiography, he was generally acknowledged to be a leading authority in vascular diseases of the eye and the optic nerve. For over 60 years, Hayreh was actively involved in basic, experimental, and clinical research in ophthalmology, publishing over 400 original peer-reviewed articles in various international ophthalmic journals, six classical monographs and books in his field of research, and more than 50 chapters in ophthalmic books. He made many seminal observations dealing with the ocular circulation in health and disease, the optic disc and the optic nerve, retinal and choroidal vascular disorders, glaucomatous optic neuropathy, fundus changes in malignant arterial hypertension, ocular neovascularization, rheumatologic disorders of the eye, and nocturnal arterial hypotension. He was an elected fellow of the National Academy of Medical Sciences.
Autoimmune optic neuropathy (AON), sometimes called autoimmune optic neuritis, may be a forme fruste of systemic lupus erythematosus (SLE) associated optic neuropathy. AON is more than the presence of any optic neuritis in a patient with an autoimmune process, as it describes a relatively specific clinical syndrome. AON is characterized by chronically progressive or recurrent vision loss associated with serological evidence of autoimmunity. Specifically, this term has been suggested for cases of optic neuritis with serological evidence of vasculitis by positive ANA, despite the lack of meeting criteria for SLE. The clinical manifestations include progressive vision loss that tends to be steroid-responsive and steroid dependent.
Normal tension glaucoma (NTG) is an eye disease, a neuropathy of the optic nerve, that shows all the characteristics of primary open angle glaucoma except one: the elevated intraocular pressure (IOP) - the classic hallmark of glaucoma - is missing. Normal tension glaucoma is in many cases closely associated with general issues of blood circulation and of organ perfusion like arterial hypotension, metabolic syndrome, and Flammer syndrome.
Helen Victoria Danesh-Meyer is a New Zealand ophthalmology academic, and as of 2008 is a full professor at the University of Auckland.
The visual pathway consists of structures that carry visual information from the retina to the brain. Lesions in that pathway cause a variety of visual field defects. In the visual system of human eye, the visual information processed by retinal photoreceptor cells travel in the following way:
Retina→Optic nerve→Optic chiasma →Optic tract→Lateral geniculate body→Optic radiation→Primary visual cortex
Diabetic papillopathy is an ocular complication of diabetes mellitus characterized by optic disc swelling and edema of optic nerve head. The condition may affect both type 1 and type 2 diabetic patients.