In the era of OCT, is detection of early papilledema using Frisen scale grading valid? A study to evaluate the role of spectral domain-OCT in papilloedema among the population of hilly areas of Northern India

Shreyanshi Sharma; Rajeev Tuli; Sushil Ojha; Neeraj K Saraswat; Gaurav Sharma

doi:10.4103/tjosr.tjosr_15_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 60 | Issue : 2 | Page : 152-157

In the era of OCT, is detection of early papilledema using Frisen scale grading valid? A study to evaluate the role of spectral domain-OCT in papilloedema among the population of hilly areas of Northern India

Shreyanshi Sharma¹, Rajeev Tuli², Sushil Ojha¹, Neeraj K Saraswat¹, Gaurav Sharma²
¹ Department of Ophthalmology, Government Doon Medical College, Dehradun, Uttarakhand, India
² Department of Ophthalmology, Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India

Date of Submission	25-Jan-2022
Date of Decision	11-Feb-2022
Date of Acceptance	30-Mar-2022
Date of Web Publication	30-Jun-2022

Correspondence Address:
Neeraj K Saraswat
Assistant Professor (Ophthalmology), Government Doon Medical College, Dehradun, Uttarakhand
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_15_22

Abstract

Context: Papilloedema is defined as optic disc oedema secondary to raised intracranial pressure (ICP). Grading the degree of oedema using only subjective, examiner-dependent and non-quantitative fundoscopic classification like Modified Friesen Clinical Scale (MFS), may be subject to errors even when used by experienced examiners. The use of spectral-domain optical coherence tomography (SD-OCT), a non-invasive imaging technique, for early identification of raised ICP even before the clinical appearance of papilloedema by quantifying the thickness of the peripapillary retinal nerve fibre layer (ppRNFL) is crucial for such patients. Aims: To evaluate the ppRNFL using SD-OCT in patients with papilloedema. Settings and Design: Hilly North Indian population, Prospective case-control study. Methods and Material: From January 2018 to December 2018, a total of 45 patients diagnosed with papilloedema were included. Age and sex-matched controls were recruited. Detailed demographic information and the history of study subjects were noted. All subjects underwent systemic and detailed ophthalmic examination. Disc photographs were graded as per Modified Frisen Criteria (MFS). SD-OCT of the optic nerve head was done to provide a mean peripapillary RNFL thickness parameters in the different quadrants of the disc in each eye. Statistical Analysis Used: For analysis, statistical software SPSS version 23 and appropriate statistical tests were applied. P value < 0.05 was considered significant. Results: The median age of presentation was 36 years (Range 10–68 years). The male to female ratio was 1:1.3. The mean ppRNFL thickness of both right and left disc in all quadrants was significantly higher in cases in comparison to controls (P-value < 0.05 is significant). The average ppRNFL thickness in all the quadrants of both eyes was significantly higher in the mild grade of papilloedema in comparison to controls (P-value < 0.05 is significant). Conclusions: SD-OCT can be ordered as a routine important non-invasive investigation in addition to basic fundoscopic examination in all patients with papilloedema or suspected to have papilloedema.

Keywords: Frisen scale, optical coherence tomography, papilloedema, peripapillary RNFL

How to cite this article:
Sharma S, Tuli R, Ojha S, Saraswat NK, Sharma G. In the era of OCT, is detection of early papilledema using Frisen scale grading valid? A study to evaluate the role of spectral domain-OCT in papilloedema among the population of hilly areas of Northern India. TNOA J Ophthalmic Sci Res 2022;60:152-7

How to cite this URL:
Sharma S, Tuli R, Ojha S, Saraswat NK, Sharma G. In the era of OCT, is detection of early papilledema using Frisen scale grading valid? A study to evaluate the role of spectral domain-OCT in papilloedema among the population of hilly areas of Northern India. TNOA J Ophthalmic Sci Res [serial online] 2022 [cited 2023 Mar 24];60:152-7. Available from: https://www.tnoajosr.com/text.asp?2022/60/2/152/349508

Introduction

The term 'papilloedema' is defined as optic disc oedema secondary to raised intracranial pressure (ICP). It is frequently bilateral and symmetric but maybe asymmetric or unilateral. In the USA, the annual incidence has been estimated to be 0.9/1 lac persons in the general population and 3.5/1 lac persons in females of 15–44 years age group.^[1] The etiology for raised ICP maybe known (e.g., brain tumor, meningitis, cerebral venous sinus thrombosis (CVS) or maybe unknown (i.e., idiopathic).^[2]

For the early diagnosis and follow-up of papilloedema, it is important to assess the visual function, fundoscopic changes and visual field by automated perimetry. In the acute stage of papilloedema, the most common and often the only visual field change observed is the enlargement of the blind spot.^[3] With protracted and severe papilloedema, nerve fibre layer visual field defects occur which are typically related to nerve fibre bundle damage at the level of the optic disc.^[4] The papillomacular bundle and thus central visual acuity appear spared until later stages of the disease.^[5] However, grading of the degree of oedema using only fundoscopic classification like the Modified Friesen Clinical Scale (MFS), which are subjective, examiner-dependent and non-quantitative, even when used by experienced examiners may be subject to errors.^[6] The use of spectral-domain optical coherence tomography (SD-OCT), a non-invasive imaging technique, has led to the identification, management, and follow-up of raised ICP even before the clinical appearance of papilloedema by quantifying the thickness of the peripapillary retinal nerve fibre layer (RNFL) thereby leading to early diagnosis and intervention preventing visual loss.^[7],[8]

In the Indian scenario, especially in the Northern hilly population, there are not much data available on the role of spectral domain-OCT in these patients. Hence, this study was aimed to assess the difference in thickness of peripapillary retinal nerve fibre layer in patients with papilloedema and normal individuals of the hilly population using SD-OCT.

Subjects and Methods

Type of study: Prospective case-control study

The study was conducted among the patients diagnosed with papilloedema attending the outpatient department (OPD) for the duration of 1 year from January 2018 to December 2018 after obtaining the permission from institutional ethics committee (IEC). Age and sex-matched controls were recruited from the patients attending Ophthalmology OPD with non-neurological complaints and those who did not meet the exclusion criteria of the cases. An equal number of cases and controls were included. All cases and controls were registered, and informed consent was taken from them for the study.

Inclusion criteria for cases

All patients diagnosed with papilloedema and willing to participate in the study.

Exclusion criteria for cases

Individuals not giving consent/uncooperative.
Less than 10 years of age.
Patients having poor vision due to a high degree of ametropia [refractive error greater than 5 dioptres], glaucoma, optic disc drusens, media opacities and any previous retinal disease.
Any previous neurological disease other than idiopathic intracranial hypertension (IIH) or subdural/subarachnoid hemorrhage (SAH).

Methodology

The study subjects (cases and controls) demographic information like name, age, sex (male/female), occupation, address, etc., detailed history of symptoms including defective vision for distant and near, headache, double vision, transient visual obscuration, altered sensorium, nausea and vomiting were noted. Past history of any similar previous episode, hypertension, diabetes, any other systemic illness, head injury, brain tumour, ocular infection, surgery or trauma and drug use like tetracycline, minocycline, etc., were enquired. The examination included general systemic physical examination including pulse, blood pressure and thorough ophthalmic examination. Subject′s both eyes were examined for distant uncorrected visual acuity (using Snellen's chart) along with pinhole corrected visual acuity, colour vision by Ishihara's chart, Intraocular pressure (in mm of Hg) using non-contact tonometer, any swelling, erythema, protrusion, deviation of the eyeball, extraocular movements (ductions and versions) in all cardinal positions of gaze, pupil size and reaction including assessment for relative afferent pupillary defect (RAPD) by swinging flashlight examination. Detailed slit-lamp examination (Haag Striet BM 900) of both eyes to see any media opacity, the status of the lens (cataract, pseudophakia, aphakia) and vitreous (for pigments, cells and opacities) was performed. Visual fields were evaluated using Humphrey automated perimetry (Zeiss Meditech) with a 30-2 program. Dilated fundus evaluation was done using direct ophthalmoscope [Heine beta 200s] or using + 90D aspheric lens (Volk) and slit-lamp bio-microscope. Following features were noted in fundus examination: Size, shape and colour of the optic disc, cup size, cup disc ratio, blurring of disc margins, haemorrhages over the disc, tortuosity of the vein, venous pulsation. Fundus photograph was taken using fundus camera VISUCAM (Zeiss Meditech). Disc photographs were graded as per Modified Frisen Criteria (MFS) [Table 1]. Frisen grade 1 and 2 as mild, grade 3 as moderate and grade 4 and 5 as severe papilloedema were considered for the study. Magnetic resonance imaging (MRI) and computerized tomography (CT scan) were advised in specific cases. OCT of the optic nerve head was done using iVue 100 SD-OCT version 2016. The subjects were asked to gaze at the fixation light within the machine for foveolar fixation, confirmed by observing the retina through the infrared monitoring camera to ensure exact motion-free centration. Measurements of peripapillary retinal nerve fibre layer (pp RNFL) thickness from 3 good quality scans (signal strength more than 6) were averaged to provide a mean peripapillary RNFL thickness parameters in the different quadrants (superior, inferior, nasal and temporal) of the disc in each eye.

Table 1: Modified Frisen scale classification

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Statistical analysis

Appropriate statistical tests were applied, and P value < 0.05 was considered significant. For analysis, statistical software SPSS version 23 was utilized.

Results

Forty-five patients with papilloedema along with 45 age and sex-matched controls over the duration of 1 year were included in the study. For cases, the median age of presentation was 36 years (Range 10–68 years), and male to female ratio was 1:1.3. [Table 2] shows a comparison of demographic characteristics among the subjects (Cases and controls) of the study population. In the present study, headache (100%) was the most common presenting complaint among the patients. In 20% of the cases, enlargement of blind spot was observed. [Table 3] shows the frequency of presenting complaints and clinical characteristics among cases (n = 45). On fundoscopic examination, papillodema was mild in 16 (35.5%), moderate in 7 (15.5%) and severe in 22 (48.8%) cases. It was also observed that the mean peripapillary RNFL thickness of both right and left disc in all quadrants was significantly higher in cases in comparison to controls [[Table 4], P value < 0.05 was significant]. The average peripallary RNFL thickness in all the quadrants of both eyes was significantly higher in the mild grade of papilloedema in comparison to controls [[Table 5], P value < 0.05 is significant]. [Table 6] shows a comparison of peripapillary RNFL thickness among different grades of papilloedema depicting statistically significant peripapillary RNFL thickening in all the quadrants between mild and severe grades of papilloedema, between moderate and severe grades of papilloedema (except nasal quadrant). There was a strong positive correlation between mean RNFL thickness and MFS grade (Spearmann correlation coefficient, r = 0.874, P < 0.0001). On comparison of area under a receiver operating characteristic (ROC) curve between healthy (controls) and peripapillary oedematous eyes (cases), it was found significantly higher (P < 0.0001) in all the quadrants for cases compared to controls. [Table 7], [Figure 1]. The cut-off values of sectoral thickness showing the highest combination of specificity and sensitivity among parameters were also calculated from ROC curves [Table 8].

Table 2: Comparison of demographic characteristics among study subjects

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Table 3: Presenting complaints and clinical characteristics among cases (n = 45)

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Table 4: Comparison of peripapillary RNFL (n = 90) among cases and controls

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Table 5: Comparison of peripapillary RNFL thickness among controls and mild grade of papilloedema

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Table 6: Comparison of peripapillary RNFL thickness among different grades of papilloedema in cases

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Table 7: ROC Curve characteristics

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Table 8: Diagnostic values showing cut-off values of different sectoral peripapillary RNFL thickness on the basis of maximum sensitivity and maximum specificity

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Figure 1: Receiver operating curve (ROC) depicting sensitivity and specificity of sectoral peripapillary RNFL thickness for cases

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Discussion

Papilloedema can present with varied clinical symptoms, neuro-ophthalmic signs and radiological features. It is characterised by elevated cerebrospinal fluid pressure because of different causes. Due to continuity of optic nerve sheath with the subarachnoid space of the brain, increased intracranial pressure is transmitted through the optic nerve which causes engorgement and anterior bulging of fibers of the retinal ganglion cells presenting as optic disc elevation. The Inferior, Superior, Nasal, Temporal (ISNT) rule states that the thickness of the neuroretinal rim along the cardinal meridians of the optic disc decreases in the order of inferior > superior > nasal > temporal quadrant; thus, inferior quadrant has the highest peripapillary RNFL thickness, and the temporal quadrant is the thinnest.^[9] OCT is a replicable, noninvasive technique of visualisation of the retina that enables quantitative evaluation of effects of intra- or extracellular oedema, and thinning of peripapillary RNFL associated with axonal loss at each phase in monitoring papillodema.^[10],[11] Peripapillary RNFL thickness is a useful parameter for differentiating papilloedema from pseudopapilloedema as well as controls, as it provides quantitative information on structures at or near the initial site of axoplasmic flow stasis and oedema. Chen and Wall quoted that the female gender is a risk factor for IIH as almost 90% of the affected population were obese females while in our study, we found 62.22% of the patients had IIH as their etiology [Table 3].^[12] Our patients presented with the most common complaint of headache (100% patients) followed by the blurring of vision (15.6%) which are in agreement with findings by Ambika et al.^[13] The majority of the patients had good visual acuity (77.7% eyes) which is in concordance to the study by Rani et al. (77.4%).^[14] This can be attributed to the acute onset of symptoms of papilloedema in most of the patients. Our study showed statistically significant thickening (P-value < 0.0001) of peripapillary RNFL in all quadrants of both rights and left optic disc cases in comparison to controls. It is in concordance with the study done by Ahuja et al.^[15] Our results are also in agreement with Fard et al.,^[16] who reported that average and all sectoral RNFL thicknesses were greater in papilloedema eyes than pseudo-papilloedema and control subjects. However, RNFL thickness was not statistically different between pseudopapilloedema and control eyes. In our study, all sectors of RNFL thickness had an AUC of more than 0.9 for differentiating papilloedema from healthy controls. Pardon et al.,^[17] have shown an AUC of 0.78 for differentiating all grades of papilloedema from pseudo-papilloedema and 0.70 for differentiating mild papilloedema from pseudo-papilloedema. In comparison of peripapillary RNFL thickness in all the quadrants for mild cases of papilloedema between cases and controls, our study showed a statistically significant difference which is similar to the finding reported by Rebolleda et al.^[8] A strong positive correlation was seen between average peripapillary RNFL thickness and MFS grading (r = 0.87, P < 0.0001) [Figure 2] which is commensurable to study done by Scott et al.,^[6] who reported similar findings (r = 0.87). Among cases with papilloedema on comparison of peripapillary RNFL thickness in all the quadrants between various MFS grades, a statistically significant result was found only for mild versus severe grade and moderate versus severe grade of papilloedema. However, this difference was not statistically significant between mild versus moderate grades. It is comparable to a study done by Vardanian et al.,^[18] in which a statistically significant difference was seen in the mild and moderate-severe grades of papilloedema. Papilloedema develops secondary to increased intracranial pressure due to varied etiology which can be serious and life-threatening. It has been seen that there is a high degree of discrepancy in the fundus grading of papilloedema even among expert examiners.^[19] In our study, it was quite evident that there was a statistically significant average peripapillary RNFL thickening in all the quadrants in mild cases of papilloedema. Hence, OCT being a non-invasive and quantitative tool will be very useful for all grades of papilloedema for follow-ups as it quantifies the RNFL thickness along with the diagnosis of early/mild often asymptomatic cases, so that early intervention could help in preventing visual loss, sometimes life-saving also.

Figure 2: A line diagram showing a linear relationship between the average RNFL thickness and modified Frisen grading of papilloedema

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Conclusion

In our study, we have observed that there was a statistically significant thickening of peripapillary RNFL thickness in all the quadrants in patients with papilloedema as compared to healthy controls. A strong positive correlation was found between RNFL thickness and the Frisen scale for grading papilloedema. Statistically significant peripapillary RNFL thickening was also seen in mild cases of papilloedema in comparison to controls

Hence, we conclude that in the current era of technological advancement, OCT is a reliable diagnostic tool with high sensitivity even in early papilloedema, and can be ordered as a routine important non-invasive investigation in addition to basic fundoscopic examination in all patients with papilloedema or suspected to have papilloedema.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Radhakrishnan K, Ahlskog JE, Cross SA, Kurland LT, O'Fallon WM. Idiopathic intracranial hypertension (pseudotumorcerebri). Descriptive epidemiology in Rochester, Minn, 1976 to 1990. Arch Neurol 1993;50:78-80.
2.	Lee AG, Wall M. Papilloedema: Are we any nearer to a consensus on pathogenesis and treatment? Curr Neurol Neurosci Rep 2012;12:334-9.
3.	Orbett JJ, Jacobson DM, Mauer RC, Thompson HS. Enlargement of the blindspot caused by papilloedema. Am J Ophthalmol 1988;105:261-5.
4.	Grehn F, Knorr-Held S, Kommerell G. Glaucomatous like visual field defects in chronic papilloedema. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1981;217:99-109.
5.	Wall M, George D. Visual loss in pseudotumorcerebri. Incidence and defects related to visual field strategy. Arch Neurol 1987;44:170-5.
6.	Scott CJ, Kardon RH, Lee AG, Frisén L, Wall M. Diagnosis and grading of papilloedema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch Ophthalmol 2010;128:705-11.
7.	Savini G, Bellusci C, Carbonelli M, Zanini M, Carelli V, Sadun AA, et al. Detection and quantification of retinal nerve fibre layer thickness in optic disc oedema using stratus OCT. Arch Ophthalmol 2006;124:1111-7.
8.	Rebolleda G, Muñoz-Negrete FJ. Follow-up of mild papilloedema in idiopathic intracranial hypertension with optical coherence tomography. Invest Ophthalmol Vis Sci 2009;50:5197-200.
9.	Chan EW, Liao J, Foo RC, Loon SC, Aung T, Wong TY, et al. Diagnostic performance of the ISNT rule for glaucoma based on the Heidelberg retinal tomograph. Transl Vis Sci Technol 2013;2:2.
10.	Rebolleda G, Diez-Alvarez L, Casado A, Sánchez-Sánchez C, de Dompablo E, González-López JJ, et al. OCT: New perspectives in neuro-ophthalmology. Saudi J Ophthalmol. 2015;29:9-25.
11.	Optical Coherence Tomography Substudy Committee, NORDIC Idiopathic Intracranial Hypertension Study Group. Papilloedema outcomes from the optical coherence tomography substudy of the idiopathic intracranial hypertension treatment trial. Ophthalmology 2015;122:1939–45.e2.
12.	Chen J, Wall M. Epidemiology and risk factors for idiopathic intracranial hypertension. Int Ophthalmol Clin Internet 2014-2016;54:1-11.
13.	Ambika S, Arjundas D, Noronha V, Anshuman. Clinical profile, evaluation, management and visual outcome of idiopathic intracranial hypertension in a 67 neuro-ophthalmology clinic of a tertiary referral ophthalmic centre in India. Ann Indian Acad Neurol 2010;13:37-41. [PUBMED] [Full text]
14.	Rani MR, Anandhi D, Anandan H, Yogeswari A, Ali JM. Multidisciplinary approach to papilloedema: A prospective case series. Int J Sci Stud 2016;4:68-70.
15.	Ahuja S, Anand D, Dutta TK, Roopesh Kumar VR, Kar SS. Retinal nerve fibre layer thickness analysis in cases of papilloedema using optical coherence tomography – A case control study. Clin Neurol Neurosurg 2015;136:95-9.
16.	Fard MA, Sahraiyan A, Jalili J, Hejazi M, Suwan Y, Ritch R, et al. Optical coherence tomography angiography in papilloedema compared with pseudopapilloedema. Invest Ophthalmol Vis Sci 2019;60:168-75.
17.	Pardon LP, Cheng H, Tang RA, Saenz R, Frishman LJ, Patel NB. Custom optical coherence tomography parameters for distinguishing papilloedema from pseudopapilloedema. Optom Vis Sci 2019;96:599-608.
18.	Vardanian V, Nguyen AM, Balmitgere T, Bernard M, Tilikete C, Vighetto A. Detection of mild papilloedema using spectral domain optical coherence tomography. Br J Ophthalmol 2012;96:375-9.
19.	Sinclair AJ, Burdon MA, Nightingale PG, Matthews TD, Jacks A, Lawden M, et al. Rating papilloedema: An evaluation of the Frisén classification in idiopathic intracranial hypertension. J Neurol 2012;259:1406-12.