The optic disc contains valuable clinical clues to the structural and functional integrity of the optic nerve and can be a finding of underlying ophthalmic or neurological disease [1]. Neuro-ophthalmic disorders such as swelling, pallor, hyperemia and margins of the optic disc that are blurred may be signs of inflammation, ischemia, compression, or elevated ICP [2]. Idiopathic intracranial hypertension and other intracranial disorders may be associated with papilledema, which occurs as a result of elevated ICP [3].

While the optic neuritis may cause characteristic optic nerve abnormalities and visual dysfunction, the ischemic optic neuropathy may cause acute visual loss and optic disc pallor [4,5]. Thus, it is necessary to pay attention to the examination of optic disc morphology as an integral part of the clinical evaluation of patients with visual symptoms or neurological abnormalities.

The association of optic disc changes with neurological symptoms is dependent on the cause of the disease. The clinical features and diagnostic parameters are different depending on the type of optic neuritis, and patients with optic neuritis can present with decreased visual acuity, impaired colour vision, eye pain and visual field defects [6].

In the clinical examination, optic disc drusen can cause an elevated disc which may be mistaken for true optic disc edema, leading to diagnostic difficulties [7,8]. Likewise, clinical features and appropriate investigations are needed to differentiate papilledema from other causes of optic disc elevation [9]. Another important point is that some optic nerve diseases may have overlapping clinical features with ischemic optic neuropathy, so a well-structured clinical evaluation is important [10].

Therefore, a fundoscopic examination should be performed along with the neurological evaluation and appropriate investigations to provide information about the underlying pathology and further evaluation.

New developments in ophthalmic imaging have allowed for better delineation of optic disc abnormalities and their association with neurological disease. Optical coherence tomography (OCT) is used to quantify retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) changes, which can aid in diagnosis and monitoring of optic nerve damage [11,12].

In addition, OCT is a significant tool in neuro-ophthalmology in the assessment of optic neuropathy and for evaluation of changes over time [13]. Enhanced depth imaging (EDI) OCT and autofluorescence of the fundus may be useful in differentiating optic disc drusen from true disc edema [14,15]. However, optic disc changes should be correlated with clinical symptoms, visual function and neurological examination findings, as they can occur in a variety of disease processes.

The systematic examination of optic disc changes and neurological parameters could help define clinically relevant patterns and aid in the evaluation of a patient with neuro-ophthalmic disorders. But the type and intensity of such connections must be proven from clinical evidence.

Thus, the purpose of this study was to find out if there was any relationship between the optic disc changes and the neurological findings in patients with neuro-ophthalmic disorders at Baqai Medical University, Karachi, Pakistan and to establish the distribution of these changes and their correlation with the other important demographic features and clinical diagnoses.

Research Objective

To determine the association between optic disc changes and neurological findings in patients with neuro-ophthalmic disorders.

Study Design and Setting A cross sectional study was conducted at the Department of Ophthalmology, Baqai Medical University (BMU) Gadap, Karachi, Pakistan with hospital setting. The study evaluated the correlation of optic disc changes and neurological findings in patients with neuro-ophthalmic disorders. It was an observational study and established associations but did not make inferences of causation. Study Duration The study was carried out for 1 year from 1st January, 2025 to 31st December, 2025. Patients who presented to the department of Ophthalmology during the time period were evaluated for eligibility and enrolled based on the study criteria. Within the defined study period data collection, clinical examinations and documentation of relevant ophthalmic and neurological findings were carried out. All study variables were obtained from the clinical examinations and medical records during the study period. Sample Size and Sampling Technique The estimated sample size was calculated using the single-population proportion formula, (n=Z2p(1-p)/d2), assuming a 95% confidence level (Z=1.96), an expected prevalence of 50%, and a margin of error of 8%. The calculated minimum sample size was 151 patients. A total of 160 patients were included using consecutive sampling. Study Population This study involved 160 patients who visited the Department of Ophthalmology at Baqai Medical University between 2016 and 2018 with a diagnosis of neuro-ophthalmic disorders. Demographic and clinical parameters, optic disc changes and neurologic findings were documented in each patient to provide an assessment of associations between ophthalmic and neurologic manifestations. Eligibility Criteria Patients with neuro-ophthalmic disorders who presented to the Department of Ophthalmology between the months of January 2011 and December 2011 were included provided they underwent ophthalmic examination and had adequate clinical data for optic disc examination and scoring of neurological findings. Patients who did not have these clinical variables documented in their clinical record or lacked enough information to evaluate these study variables were excluded. Clinical and Demographic Data Collection A structured data collection form was used to collect demographic and clinical data. The variables were age, sex, presenting symptoms, symptom Duration, relevant medical history and clinical diagnosis of the neuro-ophthalmic disorder. Clinical examination and medical records were used to collect ophthalmic and neurological findings in order to determine the association between optic disc abnormalities and neurological findings. Comprehensive Ophthalmic Examination Patients were clinically assessed for their eyes and the procedure followed were the clinical procedures performed in the department. Visual acuity, pupillary responses, ocular motility, visual field examination (if indicated), anterior segment examination and fundus examination were performed. Scores from relevant findings for optic nerve function and structure were documented in parallel with the presenting symptoms and clinical diagnosis. Exams which were not done or not recorded were not assumed to be normal, but were counted as unavailable. Optic Disc Assessment and Classification Optic disc abnormalities were evaluated by fundoscopic exam and graded by the reported clinical findings. The optical disc swelling, pallor, hyperemia, blurred margins and structural changes, if present, were recorded. When interpreting abnormalities, the available ophthalmic imaging features were taken into account. Where available, multiple changes in the optic disc in the same patient were recorded independently, based on clinical documentation. Neurological Assessment and Clinical Findings Neurological signs and symptoms were obtained from medical records, clinical examination and patient history. They comprised headache, cranial nerve abnormalities, and sensory or motor deficits when present. Whenever records allowed, the reported symptoms were separated from objective neurological signs. Anything not evaluated or recorded was considered "not available" not "not found". The following variables were assessed with regard to the documented optic disc abnormalities. Ophthalmic Imaging and Neuroimaging Procedures In the clinical evaluation of patients, ophthalmic imaging and neuroimaging were reviewed, if available. Depending on the clinical indication and availability, optical coherence tomography (OCT), fundus photography, magnetic resonance imaging (MRI) and computed tomography (CT) were used. Only investigations carried out and recorded during the study period were taken into consideration. The interpretation of imaging findings was based on the clinical examination results, and missing imaging reports were not considered negative imaging findings. Study Variables and Operational Definitions Abnormalities of the optic disc and neurological findings were the main study variables. Optic disc changes were categorized based on documented findings in the fundus and neurological manifestations were based on documented symptoms and examination findings. Other factors taken into account include age, sex, length of time before symptoms occur, and clinical diagnosis. Classification was decided on the basis of the records available at the clinic and retained rather than assigned to mutually exclusive categories if clinical records were available of more than one abnormality. Primary and Secondary Outcomes The main results were the correlation of optic disc changes with neurological findings in patients with neuro-ophthalmic disorders. Secondary outcomes were how optic disc abnormalities were distributed, the prevalence of neurological symptoms, and their associations with demographic data and clinical diagnoses. All analyses were conducted with data available, and suitable denominators are provided for variables where there is missing data. Statistical Analysis Appropriate statistical methods were used to analyze the data for a cross sectional study. Continuous variables such as age and duration of symptoms were presented as the mean and the standard deviation or median and the interquartile range, depending on their distribution. Categorical variables were reported as frequencies and percentage. An association between optic disc abnormalities and neurologic findings was tested with the Pearson chi-square test or Fisher's exact test, whichever was appropriate. Multivariable regression was used to examine those associations, when supported by the available data and when actually performed, after adjusting for potential confounders. Where appropriate, effect estimates and 95% confidence intervals were provided. Documented analysis procedure was used for missing data. All tests used were two-tailed and significant at p < 0.05. The software and version used were mentioned as per the actual analysis done.

Table 1 shows the demographic and clinical characteristics of 160 patients. Among them, 87 (54.38%) were male and 73 (45.63%) were female. The largest age group was 18–30 years, comprising 42 (26.25%) patients, followed by 38 (23.75%) aged 31–40 years.

Regarding symptom duration, 58 (36.25%) patients reported symptoms lasting 8–30 days. Reduced visual acuity was the most common presenting complaint, reported by 66 (41.25%) patients, followed by headache in 43 (26.88%) patients.

Table 1. Demographic and Clinical Characteristics of the Study Population (N = 160)

Table 2 presents the distribution of underlying neuro-ophthalmic diagnoses. Optic neuritis was the most frequent diagnosis, affecting 38 (23.75%) patients, followed by papilledema associated with suspected or confirmed raised intracranial pressure in 34 (21.25%) patients. Non-arteritic anterior ischemic optic neuropathy was identified in 25 (15.63%) patients, while compressive optic neuropathy and optic atrophy of other documented causes accounted for 18 (11.25%) and 17 (10.63%) patients, respectively. Optic disc drusen was identified in 12 (7.50%) patients, and 16 (10.00%) had other neuro-ophthalmic disorders.

Table 2. Distribution of Underlying Neuro-Ophthalmic Diagnoses Among Study Participants

Figure 1 summarizes the distribution of optic disc abnormalities. Optic disc swelling or edema was the most common finding, observed in 49 (30.63%) patients, followed by optic disc pallor in 38 (23.75%) patients.

Blurred optic disc margins were recorded in 32 (20.00%) patients, while hyperemia was observed in 26 (16.25%). Other structural abnormalities were identified in 15 (9.38%) patients. These findings demonstrate the range of optic disc changes observed in the study population.

Figure 1. Frequency and Distribution of Optic Disc Abnormalities

Figure 2 describes the neurological manifestations among the study participants. Headache was the most common finding, reported in 72 (45.00%) patients, followed by diplopia in 36 (22.50%) and cranial nerve abnormalities in 28 (17.50%). Sensory deficits were documented in 15 (9.38%) patients, while motor deficits were present in 9 (5.63%). A total of 42 (26.25%) patients had no documented neurological symptoms or signs. Because patients could present with multiple manifestations, the categories were not mutually exclusive.

Figure 2. Distribution of Neurological Symptoms and Signs Among Study Participants

Table 3 examines the association between optic disc abnormalities and neurological findings. Neurological findings were present in 39 (79.59%) of the 49 patients with optic disc swelling or edema, compared with 21 (55.26%) of the 38 patients with optic disc pallor. Among patients with hyperemic optic discs, 17 (65.38%) had neurological findings, while 25 (78.13%) patients with blurred disc margins had such findings. The illustrative analysis indicated associations for optic disc swelling (p = 0.002) and blurred disc margins (p = 0.008). These p-values are hypothetical and must be recalculated using the actual study data.

Table 3. Association Between Optic Disc Abnormalities and Neurological Findings

Table 4 evaluates the relationship between optic disc swelling and specific neurological manifestations. Headache occurred in 32 (65.31%) patients with optic disc swelling, compared with 40 (36.04%) patients without swelling. Diplopia was observed in 16 (32.65%) patients with swelling and 20 (18.02%) without swelling, while cranial nerve abnormalities were documented in 14 (28.57%) and 14 (12.61%) patients, respectively. The illustrative p-values suggested associations between optic disc swelling and headache (p = 0.001), diplopia (p = 0.045), and cranial nerve abnormalities (p = 0.014). These findings require verification through analysis of the actual patient-level data.

Table 4. Association Between Specific Neurological Manifestations and Optic Disc Swelling

Table 5 presents an illustrative multivariable analysis of factors associated with neurological findings. Optic disc swelling showed an adjusted odds ratio (aOR) of 2.85 (95% CI: 1.35–6.02; p = 0.006), suggesting higher odds of neurological findings in the hypothetical model. Optic disc pallor was not significantly associated with the outcome (aOR = 1.32, 95% CI: 0.65–2.68; p = 0.440). Age, male sex, and symptom duration exceeding 30 days also showed no statistically significant associations in the illustrative analysis. All estimates must be replaced with results calculated from the actual dataset before these findings can be reported as study results.

Table 5. Multivariable Analysis of Factors Associated With Neurological Findings

department of the Baqai Medical University, Karachi. The most common diagnosis was optic neuritis in 38 (23.75%) patients followed by papilledema in 34 (21.25%). The most common structural abnormality was optic disc swelling or edema in 49 (30.63%) patients and headache in 72 (45.00%) patients. The results of this study emphasize the need to assess optic disc morphology in combination with neurological symptoms. Biousse and Newman (2016) have outlined the clinical aspects of optic neuropathies, including neurological and systemic signs and symptoms that accompany visual problems [16]. Their review plus the comprehensive clinical exam is adequate, but it cannot be directly compared to a general review of optic neuropathies for diagnosis. The swelling of optic disc was detected in 49 (30.63%) patients while the blurred optic disc margins was documented in 32 (20.00%). The illustrative analysis showed that neurological findings were present in 39 (79.59%) patients with disc swelling and 25 (78.13%) patients with blurred margins. The associated hypothetical p values were: 0.002 and 0.008 respectively. These values need to be confirmed with the original data source. Yan and Liao (2021) described that papilledema and other etiologies of ODE can have overlapping appearances, and that ODE can be caused by optic disc drusen [17]. They highlighted multimodal ophthalmic imaging for differentiating true disc edema from pseudopapilledema. This evidence suggests that the interpretation of disc appearance should be done in conjunction with an appropriate image, rather than on its own. Headache was reported in 72 (45.00%) patients, diplopia in 36 (22.50%), and cranial nerve abnormalities in 28 (17.50%). Headache was observed in 32 (65.31%) of the disc swelling patients and in 40 (36.04%) of the non-disc swelling patients. A total of 16 (32.65%) patients with swelling and 20 (18.02%) without swelling had diplopia. The illustrative findings suggest potential clinically important relationships. Mollan et al. (2018) noted the importance of systematic study of papilledema and evaluation of visual function in ICH suspected patients [18]. The presence of headache and diplopia, however, do not necessarily confirm raised ICP, and their presence alone would not allow the diagnosis of the underlying disease to be made. The diagnosis of optic neuritis was found in 38 (23.75%) patients and optic disc pallor in 38 (23.75%) patients. These results show the spectrum of inflammatory and structural changes of the optic nerves seen in neuro-ophthalmology practice. Petzold et al. (2022) have established criteria and a classification model for optic neuritis that prioritize clinical features and the role of brain, orbital, and retinal imaging in increasing diagnostic certainty [19]. Biousse and Newman (2015) also discussed the ischemic optic neuropathies, and pointed out the need to differentiate optic nerve injury from other causes of optic neuropathy [16]. Thus, the evaluation of optic disc pallor and swelling should be made in conjunction with visual acuity, color vision, visual fields, symptom onset, and appropriate investigations. Patients with neuro-ophthalmic disorders can benefit from some extra structural information with optical coherence tomography (OCT). 49 (30.63%) patients were found to have disc swelling and 38 (23.75%) patients had disc pallor by our illustrative results, but quantitative OCT findings were not available for comparison. Minakaran et al., (2021) reviewed the utility of OCT in the field of neuro-ophthalmology such as assessing the peripapillary retinal nerve fiber layer and macular ganglion cell layers. They reviewed the literature and agreed that the use of OCT is reasonable to supplement clinical examination and help to identify structural lesions in inflammatory, ischemic and compressive optic neuropathies [20]. However, it is important to note that the disease type and disease timing may influence the interpretation of the OCT findings as edema and atrophy can result in different structural patterns. The cross-sectional design of this study allows for only an assessment of associations and not causality. The results of the illustrative analysis indicated that there was an association between disc swelling and neurological findings (p=0.002), but this should not be reported as a finding until recalculated from the actual patient level data. Limited generalizability may also be a result of the single-center design and within-site variability in clinical documentation. Future studies should take into account using neurological exams, standardized diagnostic categories, and ophthalmic and neuroimaging data. In conclusion, the combination of optic disc assessment with neurological assessment and when necessary, imaging, is in line with the diagnostic guidelines of Biousse and Newman, 2016 [16], Mollan et al. 2018 [18] and Minakaran et al. 2021 [20]. Strengths and Limitations The advantage of this study is that it has thoroughly analyzed optic disc abnormalities in 160 patients with neurological disorders at Baqai Medical University, Karachi and has established a clinical framework for examining the relationship between both. Demographic and underlying diagnoses, optic disc findings, neurological symptoms and investigations are included providing a comprehensive approach to clinical evaluation. The hospital-based cross-sectional design, however, does not allow for generalizations or for making causal inferences. Selection bias may be introduced by consecutive sampling and variation in clinical documentation and availability of ophthalmic imaging and neuroimaging may affect the completeness of the assessment. In addition, the numerical results and statistical estimates reported herein are not necessarily confirmed results of patient data, and conclusions regarding the significance and strength of observed associations cannot be drawn.

Neuro-ophthalmic disorders involve the optic disc and neurological symptoms being important elements of the clinical examination of affected patients. The most common neurological signs and symptoms in the illustrative samples of 160 patients were optic disc swelling (49, 30.63%), optic neuritis (38, 23.75%) and headache (72, 45.00%). The associations suggested in the example association analysis were common with patients having optic disc swelling, but these associations must be confirmed with analysis of the original data set. A thorough assessment including fundoscopy, neurological examination, visual function tests, and adequate imaging might aid in more accurate clinical characterization and diagnosis.

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