Recently, we encountered a patient whose vision in both eyes had deteriorated.
The patient was diagnosed with senile cataract at another hospital and was preparing for surgery.
The patient is a 57-year-old male who came for medical treatment due to progressive decline in his vision in both eyes.
Before the visit, it had been diagnosed in another hospital that both eyes were suffering from senile cataracts, and an admission certificate had already been issued.
This visit of the patient was also for preparing to undergo bilateral cataract surgery.
However, during the visit, it was found that the patient's vision in both eyes did not match the degree of lens opacity, so the diagnosis of cataract was suspected.
The patient's uncorrected visual acuity:
Right eye 0.3, Left eye 0.12. The opacity of the lens is not severe and does not match the vision significantly.
Therefore, examinations such as fundus, visual field, and intraocular pressure were conducted.
Under the ophthalmoscope, the optic discs of both eyes appeared pale in color.
No abnormalities were found in the OCT of both eyes, but the nerve fiber layer was significantly thinner.
The visual field shows extensive loss in both eyes.
The right eye only retains the nasal upper quadrant, while the left eye has an almost tubular visual field.
A consultation with the neurology department was requested, and a head MRI was performed.
Apart from showing mild brain atrophy, no obvious space-occupying lesions were found.
Based on the patient's aforementioned symptoms, a diagnosis of chronic ischemic optic neuropathy in both eyes was made (there might be some limitations as I am not an expert in ophthalmology and neurology).
However, regardless of the diagnosis, the damage to the optic nerve is clear.
Therefore, the current main treatment is not cataract surgery, but rather assisting in the recovery of the optic nerve.
Hence, the patient is given Tongsai Pulse Tablets and Cytosyl Choline Capsules for oral administration.
After three months of treatment, a follow-up visit was conducted and the vision in both eyes improved significantly.
The right eye has been raised to 0.6, and the left eye to 0.5.
The visual field of both eyes has significantly expanded and improved. This indicates that the treatment is effective.
Discussion
Chronic ischemic optic neuropathy of the eyes is an ischemic optic neuropathy centered on chronic hypoperfusion of the anterior part of the optic nerve.
It belongs to the same ischemic optic neuropathy spectrum as acute non-arteritic anterior ischemic optic neuropathy (NAION), but has its own uniqueness in terms of pathogenesis, clinical manifestations and disease course evolution.
The following provides a systematic elaboration on pathophysiology, clinical features, diagnostic key points, and treatment strategies.
Pathophysiological mechanism
Fundamentals of Hemodynamics
The blood supply to the anterior part of the optic nerve mainly comes from the branches of the posterior short ciliary artery, forming the choroidal vascular network around the optic disc and the microvascular network within the optic nerve head.
This area belongs to the vascular watershed region, with limited perfusion pressure reserve.
It is extremely sensitive to systemic blood pressure fluctuations and local vascular regulatory dysfunction.
The core mechanism of chronic ischemia is not the acute occlusion of blood vessels, but rather the chronic hypoxia and metabolic stress caused by a long-term state of low perfusion.
This low perfusion can arise from:
Nighttime hypotension is an important trigger factor.
During sleep, there is a natural drop in blood pressure.
If combined with the effects of antihypertensive drugs, autonomic nerve dysfunction, or orthostatic hypotension, the optic nerve perfusion pressure can drop below the critical level.
Repeated nocturnal hypoperfusion leads to axonal transport blockage in the optic nerve and mitochondrial dysfunction.
Sleep apnea-hypopnea syndrome (OSAHS) aggravates ischemia through multiple pathways.
Repeated apnea causes nocturnal hypoxemia, hypercapnia and severe fluctuations in intrathoracic pressure, leading to endothelial dysfunction of blood vessels, hypercoagulable state of blood and activation of the sympathetic nervous system, thereby damaging the microcirculation of the optic nerve.
The decline in vascular regulatory function should also not be overlooked.
As people age, the automatic regulation ability of the posterior short ciliary arteries declines, unable to effectively respond to blood pressure fluctuations, making the optic nerve more susceptible to the effects of changes in perfusion pressure.
Organ pathological changes
Chronic ischemia leads to the chronic degeneration of retinal ganglion cell axons, rather than acute infarction.
In the early stage, there are disorders in axoplasmic transport, mitochondrial aggregation and swelling. Subsequently, axonal demyelination and Wallerian degeneration occur.
The reactive proliferation of astrocytes leads to the formation of diffuse optic nerve atrophy.
This process can take place over a period of several months to several years, explaining the chronic and progressive course of the disease observed in clinical settings.
Clinical features
Onset and Course of the Disease
The onset is insidious.
Patients often have difficulty accurately recalling the exact time of the onset.
They commonly complain of "gradual decline in vision over the past several months" or "things are becoming increasingly blurry when I look at them", which is similar to cataracts.
The decline in vision is slow and progressive, lasting for several months to several years.
There may be fluctuations during this period, especially when blood pressure is not well controlled or when the overall condition changes.
This is in sharp contrast to the sudden vision loss seen in acute NAION.
Visual impairment
Involvement of both eyes is a typical feature, but it is often asymmetrical.
One eye may develop the condition first, while the other eye becomes affected several months or years later.
The degree of visual impairment varies from mild blurred vision to severe visual impairment.
Some patients retain their central vision but experience significant decline in contrast sensitivity and color vision.
Change of perspective
In the early stage, it may present as diffuse reduction in light sensitivity or peripheral central scotoma.
As the disease progresses, arcuate defects connected to the physiological blind spot, as well as nasal step-like patterns, gradually appear.
In the later stage, they fuse into tubular visual fields or temporal island-like visual fields.
The slow progression of visual impairment reflects the gradual loss of nerve fibers.
Fundus manifestations
During the acute phase, mild congestion of the optic disc or blurred borders can be observed, but it is usually not as severe as in acute NAION.
More patients were already in the atrophic stage during their visits, presenting with diffuse or segmental pallor of the optic disc, especially on the temporal side.
Around the optic disc, there is visible exposure or atrophy of the choroid.
The retinal nerve fiber layer (RNFL) shows diffuse thinning.
Optical coherence tomography (OCT) reveals a uniform decrease in RNFL thickness across all quadrants, with the lower quadrant showing the most significant reduction.
Associated symptoms
It is usually painless and without eye movement pain.
Some patients may experience mild eye discomfort or visual fatigue.
If OSAHS is combined, there may be symptoms such as daytime sleepiness, morning headache, and memory impairment.
Key points of diagnosis
Core diagnostic criteria
The diagnosis requires the consideration of the following elements:
Chronic and progressive decline in vision in both eyes (or in one eye that subsequently develops into both eyes).
The visual field defect is consistent with the distribution of optic nerve fiber bundles.
Symptoms of optic nerve atrophy;
The intraocular pressure is normal or there is no glaucomatous damage.
There are risk factors for chronic ischemia or evidence of hemodynamic abnormalities.
Risk factor assessment
Systemic vascular risk factors: Hypertension, diabetes, hyperlipidemia, ischemic heart disease, cerebrovascular disease.
It should be noted that some patients may have been ill but have not been diagnosed, or their blood pressure or blood sugar levels may not be well controlled.
Nighttime hypotension: Carefully inquire about the timing of taking antihypertensive drugs (taking them before bedtime may aggravate nighttime hypotension), symptoms of orthostatic hypotension, and morning dizziness, etc.
24-hour ambulatory blood pressure monitoring can detect excessive nighttime blood pressure drops (where nighttime systolic blood pressure drops by more than 20% compared to daytime or is lower than 90 mmHg).
Sleep apnea-hypopnea syndrome: High-risk groups include those who are obese, have a thick neck circumference, have a receding chin, and are habitual snorers.
The Epworth Sleepiness Scale score and nocturnal blood oxygen monitoring are screening tools, while a polysomnography (PSG) is required for a definitive diagnosis.
Anatomical factors: A small optic disc, a narrow or absent optic cup (known as "high-risk optic disc") are common predisposing factors for ischemic optic neuropathy, and they are also frequently observed in patients with chronic ischemia.
Drug factors: Phosphodiesterase-5 inhibitors (such as sildenafil), amiodarone, interferon-α and other drugs are associated with ischemic optic neuropathy.
Differential diagnosis
Normal tension glaucoma (NTG): Both conditions can present with progressive optic nerve atrophy, thinning of the retinal nerve fiber layer (RNFL), and visual field defects, with normal intraocular pressure.
The key points for differentiation include: characteristic changes in the optic disc of NTG (cupping along the disc margin, enlargement and deepening of the optic cup, and peripapillary hemorrhage);
Visual field defects usually begin with nasal step-like or arc-shaped blind spots.
The progression of NTG is slower, and the course of the disease is often measured in years.
Optical coherence tomography (OCT) of the optic nerve shows that the damage pattern of NTG is more consistent with glaucoma (with thinning of the retinal nerve fiber layer (RNFL) in the superior and inferior regions being prominent).
The two can coexist and a comprehensive judgment is required.
Hereditary optic neuropathy: Autosomal dominant optic atrophy (ADOA) and Leber hereditary optic neuropathy (LHON) can present as chronic vision loss in both eyes.
The onset age of ADOA is relatively young, and most cases have a family history.
The OPA1 gene test is positive in these cases.
LHON typically presents with an acute or subacute onset, and mitochondrial DNA mutation testing can confirm the diagnosis.
Toxic/nutritional optic neuropathy: Alcohol-tobacco-induced amblyopia, vitamin B12 deficiency, etc., usually have a clear exposure history.
The central scotoma is the main symptom.
It can partially recover after quitting smoking and alcohol.
Pressure-induced optic nerve lesion: Progressive decline in vision, often accompanied by color vision impairment and central scotoma.
On MRI, a space-occupying lesion can be seen in the optic chiasm or optic nerve canal.
Auxiliary examination
Visual function assessment
The standard automatic visual field test is used to determine the type and extent of the defect.
Optical coherence tomography (OCT) is used to quantitatively measure the thickness of the retinal nerve fiber layer (RNFL) and the thickness of the macular ganglion cell complex (GCC), and to conduct follow-up monitoring of the progression.
Visual evoked potential (VEP) assesses the conduction function of the optic nerve.
An extended latency and decreased amplitude of the P100 wave indicate axonal damage.
The color vision test (Farnsworth D-15) can detect early blue-yellow or red-green color vision disorders.
Hemodynamic assessment
24-hour ambulatory blood pressure monitoring can identify patterns of nocturnal hypotension and blood pressure fluctuations.
Polysomnography (PSG) is used to diagnose obstructive sleep apnea-hypopnea syndrome (OSAHS), and it records parameters such as apnea-hypopnea index (AHI) and the lowest blood oxygen saturation.
Carotid artery ultrasound and transcranial Doppler (TCD) were used to assess the blood flow of the internal carotid artery and the ophthalmic artery.
Cardiac assessment (electrocardiogram, echocardiogram) is conducted to detect arrhythmias and decreased cardiac output.
Laboratory examination
Complete blood count, blood glucose, glycosylated hemoglobin, lipid profile, coagulation function, homocysteine.
The levels of vitamin B12 and folic acid rule out nutritional causes.
Genetic testing (for OPA1 and mitochondrial DNA) should be conducted when necessary.
Imaging examination
MRI plain scan and enhanced scan of the skull and orbit were performed to rule out compressive, inflammatory and demyelinating lesions.
MRI of the optic nerve can reveal the thinning of the optic nerve or abnormal signals.
Treatment strategy
Etiological treatment
Blood pressure management: Optimize the blood pressure-lowering plan, avoid taking blood pressure-lowering medication before bedtime, and prevent nocturnal hypotension.
For those with nocturnal hypotension, it may be advisable to consider changing the type of antihypertensive drugs or switching to taking the medication in the morning.
When necessary, physical measures such as lying-down and standing-up blood pressure training and elastic stockings should be adopted.
Sleep apnea treatment: Continuous airway positive pressure ventilation (CPAP) is the first-line treatment for OSAHS, which can significantly improve nocturnal hypoxia and blood pressure fluctuations, and prevent the progression of optic nerve damage.
Oral appliances and side-lying sleep can be used as supplementary measures.
Control of vascular risk factors: Patients diagnosed with hypertension, diabetes, or hyperlipidemia need strict and targeted management to achieve the required standards.
Antiplatelet therapy (aspirin) is applicable to patients with hypercoagulable state or those at high risk of cardiovascular and cerebrovascular diseases.
Improve microcirculation
Vasodilators: Calcium channel blockers (such as nimodipine) can improve blood flow in the optic nerve and retina, but blood pressure monitoring should be taken into account.
Extracts from ginkgo leaves and traditional Chinese medicine preparations such as Tongsepu Tablets have a certain effect in improving microcirculation.
Neurotrophic therapy: Cytidine diphosphate choline, as a precursor of phosphatidylcholine and acetylcholine, has functions such as membrane repair, mitochondrial protection, and antioxidant effects, and can be used as an adjunctive treatment.
Mecobalamin promotes the repair of nerve myelin sheaths.
The multivitamin B complex supports neural metabolism.
Optic nerve protection
Antioxidants: Vitamins C, E, alpha-lipoic acid, etc. can alleviate oxidative stress damage.
Intraocular pressure reduction therapy: Even if the intraocular pressure is normal, moderately lowering the intraocular pressure (for example, reducing the target intraocular pressure to 12-14 mmHg) can increase the perfusion pressure difference of the optic nerve. Some patients may benefit, especially when they have high-risk factors for glaucoma.
Rehabilitation and Follow-up
Low vision rehabilitation training helps patients adapt to the tubular visual field, using visual aids and directional walking training.
Regular follow-ups of visual field, OCT and vision are conducted to assess the therapeutic effect and the progression of the disease.
It is recommended to have a re-examination every 3 to 6 months.