Causes and Clinical Characteristics of Compressive Optic Neuropathy in South Korean Patients
Article information
Abstract
Purpose
We aimed to investigate the causes and clinical features of compressive optic neuropathy in Koreans.
Methods
We analyzed the medical records of patients diagnosed with compressive optic neuropathy from March 2014 to December 2023 to determine the cause of optic nerve compression, symptoms and symptom patterns at first visit, accompanying symptoms, types of visual field defects, and visual prognosis after surgery. In addition, the results of visual field tests and optical coherence tomography were analyzed to determine the positivity rate of each test and factors affecting test results.
Results
A total of 73 patients were diagnosed with compressive optic neuropathy, and the most common cause was pituitary tumor (37 patients, 50.7%) followed by meningioma (16 patients, 21.9%), hemangioma (4 patients, 5.5%), thyroid ophthalmopathy (4 patients, 5.5%), and paranal sinus tumor tumor (2 patients, 2.7%). In terms of symptom pattern, half of the patients had vision and visual field defects that appeared gradually (41 patients, 56.2%), but there were also quite a few patients whose symptoms appeared suddenly (17 patients, 23.3%). The positivity rate of the diagnostic test was highest for visual field testing (89.0%). In pituitary tumors, tumor size affected diagnostic test results (p = 0.01).
Conclusions
The most common cause of compressive optic neuropathy in South Koreans was a pituitary tumor. Deterioration of visual function can also occur acutely, and visual field testing was useful for diagnosis.
Various space-occupying lesions can occur around the optic nerve head, intraorbital, and intracranial optic nerve to the optic chiasm and occipital lobe. When pressure is applied to the optic nerve and visual pathway, compressive optic neuropathy may occur. It is mainly caused by neoplastic diseases such as pituitary adenoma and meningioma and non-neoplastic diseases such as thyroid ophthalmopathy, but can also be caused by vascular diseases such as cerebral aneurysm [1,2]. Because compressive optic neuropathy is often caused by tumors that grow relatively slowly, such as pituitary adenoma, ophthalmic symptoms such as vision and visual field defects often appear gradually. However, depending on the cause, symptoms may occur rapidly and may also be accompanied by various neurological symptoms such as headaches and dizziness [3]. In addition, visual acuity, color vision, and visual field tests are used to diagnose compressive optic neuropathy, but recently, with the development of optical coherence tomography (OCT), it has been reported to be useful in diagnosing compressive optic neuropathy [4–6]. The causes, clinical features, and diagnostic tests of compressive optic neuropathy are well known in studies targeting overseas patients, but there is no research targeting in South Korean patients yet. Therefore, in this study, we investigated the causes and clinical aspects of compressive optic neuropathy in South Korean patients and attempted to analyze what tests are important for diagnosis.
Materials and Methods
Ethics statement
This study was approved by the Institutional Review Board of Chosun University Hospital (No. 2023-04-011-001). Written informed consent was waived due to the retrospective study design. The study was conducted in accordance with the Declaration of Helsinki.
Study design
We retrospectively analyzed the medical records of patients who visited the ophthalmology department or were transferred from other departments and diagnosed with compressive optic neuropathy from March 2014 to December 2023. The diagnostic criteria for compressive optic neuropathy were the presence of optic neuropathy in visual acuity, visual field, color vision, and fundus examination, and the discovery of compressive lesions directly related to this in imaging tests. Those who showed signs of cerebral hemorrhage or cerebral infarction in addition to compressive lesions on imaging tests or had a history of such lesions (history of trauma more than a concussion, being treated or had a history of glaucoma, or history of retinal or cataract surgery, etc.) were excluded. Patients with a history of ophthalmic surgery were also excluded. Patients with systemic diseases such as diabetes, hypertension, and hyperlipidemia but no ophthalmic complications were included. Patients with hyperthyroidism, myasthenia gravis, and ocular motor cranial nerve palsy were also included.
All patients’ sex, age at diagnosis, ophthalmic symptoms, accompanying symptoms, symptom pattern, symptom duration from symptom onset to ophthalmological examination, and follow-up after surgical treatment were confirmed through medical records. The results of basic ophthalmic tests such as slit-lamp microscopy, intraocular pressure, and refraction were confirmed, and the results of visual acuity, visual field, color vision, and fundus examination were analyzed. In addition, OCT was performed to analyze the peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular ganglion cell inner plexiform layer thickness (mGCIPLT). The results of brain magnetic resonance imaging and computed tomography were confirmed and the diagnosis, location, and size of the lesion were analyzed. For visual field testing, a static automatic visual field analyzer (Humphrey Visual Field Analyzer, Carl Zeiss Meditec) was used, and cases with fixation loss of more than 20% and false positives or false negatives of more than 33% were excluded from the analysis. The positive criterion for a visual field test is when 3 points with a probability of <5% are gathered on the pattern deviation map, or when there is 1 point with a probability of <1% or 2 points with a probability of <1% are gathered across the vertical meridian. OCT was measured using Cirrus HD-OCT (Carl Zeiss Meditec), and cases with a signal intensity of 6 or less were excluded from the analysis. The positive criterion for pRNFLT was when yellow or red appeared on the nasal or temporal side on the RNFL quadrants map, and the positive criterion for mGCIPLT was when yellow or red appeared on the superior-medial or inferior-medial side on the ganglion cell analysis sector map.
Based on the above results, we investigated the causative diseases of compressive optic neuropathy and the types of diseases that cause acute ophthalmic symptoms. The type of visual field defect was analyzed, and the positive rate of visual field test and OCT were compared to identify a useful test method for diagnosing compressive optic neuropathy. In addition, patients with pituitary tumors were classified separately, the results of visual field tests and OCT were analyzed, and the size of the tumor was measured in imaging tests. The size of the tumor was measured as the length of the longest vertical diameter of the tumor on the sagittal view of the brain magnetic resonance image. Based on this, we analyzed the relationship between symptom duration and tumor size and the positive rate of visual field tests and the positive rates of pRNFLT and mGCIPLT in OCT. Symptom duration was defined as the period of decreased visual acuity or visual field. Furthermore, we analyzed the visual prognosis of patients who were followed up after pituitary tumor surgery.
Statistical analysis
Statistical analysis was performed using IBM SPSS ver. 26.0 (IBM Corp). The statistical methods Dunnett T3 test and Games-Howell test were used. A p-value of <0.05 was defined as significant.
Results
A total of 73 patients (117 eyes) were diagnosed with compressive optic neuropathy, and the average follow-up period was 24.9 ± 24.4 months (range, 0–119.5 months). The average age at diagnosis was 54 ± 16.1 years (range, 7–85), and there were 35 men (47.9%) and 38 women (52.1%). At the first visit, the average visual acuity of the normal eyes was 0.86 (logarithm of the minimum angle of resolution [logMAR], 0.069) ± 0.13 (range, 0.25–1.0) based on Snellen, and 0.13 (logMAR, 0.88) ± 0.13 (range, no light perception to 1.0) for the symptomatic eyes. At the final follow-up, the average visual acuity of the symptomatic eyes was 0.10 (logMAR, 1.00) ± 0.10 (range, no light perception to 1.0). The average color vision was 13.9 ± 2.80 (range, 1–15) in the normal eyes and 7.6 ± 6.32 (range, 0–15) in the symptomatic eyes among the 15 plates of the Ishihara color vision test table. The most common cause of compressive optic neuropathy was pituitary tumor (37 patients, 50.7%), followed by meningioma (15 patients, 21.9%), hemangioma (4 patients, 5.5%), thyroid ophthalmopathy (4 patients, 5.5%), and paranasal sinus tumor (2 patients, 2.7%). The most common ophthalmic symptoms were decreased visual acuity. (46 patients, 63.0%), followed by visual field defects, double vision, ptosis, and eye pain. There were 16 cases (21.9%) without symptoms. As for accompanying symptoms, 19 patients (26.0%) complained of headaches, and other symptoms included dizziness, vomiting, nausea, and cognitive impairment. The majority of the patients (41 patients, 56.2%) had ophthalmic symptoms gradually and chronically, but there were also quite a few (17 patients, 23.3%) that showed acute symptoms. The causative disease among patients complaining of acute symptoms was pituitary apoplexy (five patients), hemangioma, metastatic tumor, sinus disease, meningioma, and aneurysm (Table 1).
Causes of compressive optic neuropathy
The most common pattern of visual field defect was temporal hemianopia in 32 patients (43.8%), followed by total blindness, scotoma, altitudinal defect, homonymous visual field defect, and nasal visual field defect (Table 2). The positive rate of diagnostic tests was the highest in visual field testing at 65 patients (89.0%), followed by OCT with pRNFLT positive rate in 30 patients (41.1%) and mGCIPLT positive rate in 47 patients (64.4%). As a result of separately classifying and analyzing 37 patients with pituitary tumors, the positive rate of visual field test was the highest at 30 patients (81.1%), followed by the positive rate of pRNFLT in 16 patients (43.2%) and the positive rate of mGCIPLT in 27 patients (73.0%). Pituitary tumor patients were classified as follows based on the test results: 10 in the visual field test positive group, 7 in the mGCIPLT positive group, 4 in both the visual field test and mGCIPLT positive group, and 16 in the visual field test, mGCIPLT, and pRNFLT positive group. The average tumor size of pituitary tumor patients was 23.853 mm (visual field test positive group, 21.774 mm; mGCIPLT positive group, 18.964 mm; visual field test and mGCIPLT positive group, 23.749 mm; and visual field test, mGCIPLT, and pRNFLT positive group, 25.439 mm). The tumor size in the mGCIPLT positive group was smaller than the visual field test, mGCIPLT, and pRNFLT positive group (p = 0.01) (Fig. 1). Additionally, the visual field test positive group tended to have a shorter symptom period than other groups, but there was no statistical significance (p = 0.19) (Fig. 2). Among 10 patients who were followed up after pituitary tumor surgery, 5 patients in the vision recovery group whose vision improved by more than 15 letters or visual field defects significantly improved, and 5 patients in the non-vision recovery group were analyzed. There was no significant change in pRNFLT and mGCIPLT before and after surgery in both groups, and although there was no statistical significance, the vision recovery group tended to have smaller tumor size (p = 0.200) and shorter symptom duration (p = 0.340) than the non-vision recovery group.
Visual field defect patterns of compressive optic neuropathy patients
Relationship between tumor size and diagnostic results in patients with pituitary adenoma. mGCIPLT = macular ganglion cell inner plexiform layer thickness; pRNFLT = peripapillary retinal nerve fiber layer thickness.
Relationship between symptom period and diagnostic results in patients with pituitary adenoma. mGCIPLT = macular ganglion cell inner plexiform layer thickness; pRNFLT = peripapillary retinal nerve fiber layer thickness.
Discussion
Common causes of compressive optic neuropathy include optic nerve glioma, optic nerve sheath meningioma, and metastatic tumor that occur primarily in the optic nerve or optic nerve sheath, and pituitary adenoma that occurs in the intracranial saddle, meningioma that occurs around the saddle, and craniopharyngioma are common [1]. In addition, intraorbital inflammatory diseases such as thyroid ophthalmopathy and inflammatory tumors within the paranasal sinuses such as mucocele may spread into the orbit and put pressure on the optic nerve [7]. In a recent US study that analyzed the incidence of compressive optic neuropathy based on the population, pituitary adenoma was the most common cause, accounting for 8 out of 23 patients (35%), followed by meningioma at 17%. Aneurysms, germinoma, craniopharyngioma, thyroid ophthalmopathy, hemangioma, and optic nerve glioma were also reported to be causes of compressive optic neuropathy [3]. In our study targeting South Koreans, pituitary adenoma and meningioma were found to be the most common causes of compressive optic neuropathy, which was the same as the results of the US study. Thyroid ophthalmopathy, hemangioma, craniopharyngioma, and aneurysm were also found to be causes, which were also the causes of compressive optic neuropathy in the US study. On the other hand, in this study, paranasal mucocele and paranasal tumor were investigated as causes of compressive optic neuropathy, but they were not reported in the US study, so there was a difference. However, direct comparison is thought to be difficult because the number of patients and population distribution between this study and the US study are different.
Tumors that cause compressive optic neuropathy, such as pituitary adenomas and meningiomas, generally grow slowly, so symptoms such as decreased vision and visual field defects are also likely to occur gradually [8]. However, in diseases that can grow suddenly, such as aneurysms and pituitary apoplexy, symptoms of optic neuropathy may also occur suddenly [3]. As a mechanism for acute vision loss, the tumor itself may suddenly grow and cause acute symptoms, or as the tumor grows, it may compress the blood vessels and cause ischemic symptoms to appear suddenly [9]. In fact, in this study, although the number of patients who developed symptoms gradually was higher at 56.2%, the number of patients who developed symptoms acutely was also significantly higher at 23.3%. In addition, the causes of acute symptoms were found to be diseases that can suddenly grow, such as pituitary apoplexy (Fig. 3A–3G), hemangioma, sinus mucocele, and aneurysm. Usually, patients who experience acute vision loss are not given priority for imaging tests such as brain magnetic resonance imaging due to suspicion of ischemic or inflammatory disease. However, because the results of this study confirmed that compressive optic neuropathy can also cause acute vision loss, patients showing clinical signs of acute optic neuropathy should also prioritize imaging tests to rule out the possibility of compressive optic neuropathy.
Images of a patient with pituitary apoplexy with acute symptom. Disc photographs of (A) the right eye and (B) the left eye. (C) Peripapillary retinal nerve fiber layer (RNFL) thickness and macular ganglion cell inner plexiform layer thickness. Visual field test of (D) the left eye and (E) the right eye. (F, G) Brain magnetic resonance imaging. Only visual field test defects were confirmed. ONH = optic nerve head; OU = both eyes; OD = right eye; OS = left eye; C/D ratio = cup/disc ratio.
When compressive lesions occur in the optic nerve and optic chiasm, pRNFLT and mGCIPLT may decrease due to ganglion cell apoptosis due to retrograde degeneration [10]. High-resolution OCT is an examination equipment that can observe each layer of the retina without a biopsy. It can observe the RNFL, ganglion cell layer, and inner plexiform layer that make up the inner retinal layer. The inner retinal layer is the area directly affected when there is a compressive optic nerve lesion, and therefore, the importance of diagnosing compressive optic neuropathy using OCT is increasing. In particular, the results of OCT for patients with pituitary adenoma, the most common cause of compressive optic neuropathy, have recently been reported [4–6]. Yum et al. [4] reported that 12 of 46 eyes of 46 patients with pituitary adenoma had normal visual field tests and pRNFLT, but decreased mGCIPLT. Tieger et al. [5] reported that there were six patients with normal visual field tests but decreased pRNFLT and mGCIPLT on OCT, and in particular, mGCIPLT decreased more. Blanch et al. [6] reported that overall or nasal mGCIPLT was decreased in seven patients with pituitary adenoma, but visual field examination was normal. In our study, among 37 patients with pituitary tumors, 7 patients had normal visual field tests but decreased mGCIPLT. In particular, in this study, it was found that the seven patients with decreased mGCIPLT had smaller tumors than other patients, which suggests that if the tumor size is small, structural optic nerve damage may occur but functional visual abnormalities may not appear. In glaucomatous optic neuropathy, it is known that visual field tests may be normal until 30% to 50% of ganglion cells are damaged [11]. In other words, it is thought that a similar mechanism can be applied to compressive optic neuropathy. In the future, it will be necessary to determine whether abnormal findings appear in visual field tests in the seven patients with decreased mGCIPLT in this study when the tumor grows and more ganglion cells are damaged.
In this study, we compared the positivity rate of diagnostic tests in patients with compressive optic neuropathy. The positivity rate of the visual field test was the highest at 89%, and the positivity rate of mGCIPLT and pRNFLT of OCT was 62% and 41%, respectively. In other words, since patients with compressive optic neuropathy are more likely to have abnormal findings in visual field tests, visual field tests are thought to be important as a diagnostic test in patients with compressive optic neuropathy. In addition, this study examined the clinical characteristics of 10 patients with pituitary tumors who had positive visual field tests and no abnormal findings on OCT. Although there was no statistical significance, these patients tended to have a shorter symptom period than other patients. It is generally known that it takes about 4 to 6 weeks for optic nerve atrophy to occur after optic nerve compression occurs [12]. Additionally, it has been reported that when damage to the optic nerve or optic chiasm occurs suddenly, visual field abnormalities appear first, and it may take several weeks for OCT changes to appear [13]. In other words, if the tumor grows rapidly, it can be assumed that the visual field defect may appear only before structural optic atrophy appears. In fact, Micieli et al. [10] reported that abnormal findings may appear only in visual field tests in patients with rapidly growing tumors, such as in pituitary apoplexy, and Biousse et al. [14] also reported that abnormal findings may appear first in visual field tests when acute visual loss occurs due to compression of the optic chiasm. It has also been reported that pRNFLT and mGCIPLT can be normal for several weeks [14]. Recently, the importance of OCT in the diagnosis of compressive optic neuropathy has increased, but visual field testing is still an important test in diagnosing compressive optic neuropathy. Especially in acute compressive optic neuropathy, only visual field testing can show abnormal findings so confirmation of this is absolutely necessary. On the other hand, as mentioned in the paragraph above, mGCIPLT is thought to be useful in detecting small tumors that grow slowly. In addition, since mGCIPLT had the second highest positive rate after visual field test, it is necessarily to check both visual field and mGCIPLT at the same time to detect compressive optic neuropathy.
This study has several limitations, including the relatively small number of patients, the retrospective study design, targeting only patients who visited a tertiary institution and an ophthalmology clinic, and the duration and pattern of symptoms being dependent on the patient’s subjective memory. Additionally, not all diagnoses of compressive optic neuropathy were confirmed through biopsy and the analysis of the macular ganglion cell inner plexus layer does not accurately represent the structural form of crossed and uncrossed fibers in the macula. Furthermore, the difficulty in confirming prognosis after surgical treatment due to the low follow-up rate remains as a limitation. Additional research is needed in the future to address these limitations. However, this study is meaningful in that it reported the causes and clinical features of compressive optic neuropathy in South Koreans for the first time and emphasized the importance of imaging tests, visual field tests, and OCT in diagnosis.
In conclusion, this study confirmed that the most common cause of compressive optic neuropathy in South Koreans was a pituitary tumor. It has also observed that a decline in visual function can also occur acutely, and that visual field testing is useful for diagnosis.
Notes
Conflicts of Interest
None.
Acknowledgements
None.
Funding
This study was supported by a research fund from Chosun Universitiy Hospital in 2023.