Exploring the utility of retinal optical coherence tomography as a biomarker for idiopathic intracranial hypertension: a systematic review

This study aimed to examine the existing literature that investigated the effectiveness of optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) as a biomarker for idiopathic intracranial hypertension (IIH). Our search was conducted on January 17th, 2024, and included the databases, Medline, Scopus, Embase, Cochrane, Latin American and Caribbean Health Sciences Literature (LILACS), International Standard Randomized Controlled Trial Number (ISRCTN) registry, and the International Clinical Trials Registry Platform (ICTRP). Our final review included 84 articles. In 74 studies, OCT was utilized as the primary ocular imaging method, while OCT-A was employed in two studies including eight studies that utilized both modalities. Overall, the results indicated that IIH patients exhibited significant increases in retinal nerve fiber layer (RNFL) thickness, total retinal and macular thickness, optic nerve head volume, and height, optic disc diameter and area, rim area, and thickness compared to controls. A significant correlation was observed between cerebrospinal fluid (CSF) pressure and OCT parameters including RNFL thickness, total retinal thickness, macular thickness, optic nerve head volume, and optic nerve head height. Interventions aimed at lowering CSF pressure were associated with a substantial improvement in these parameters. Nevertheless, studies comparing peripapillary vessel density using OCT-A between IIH patients and controls yielded conflicting results. Our systematic review supports OCT as a powerful tool to accurately monitor retinal axonal and optic nerve head changes in patients with IIH. Future research is required to determine the utility of OCT-A in IIH. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-024-12481-3.


Introduction
Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology characterized by raised intracranial pressure (ICP) that predominantly affects obese women of childbearing age [1].The prevalence of IIH in the general population is 1-3 per 100,000 people but among women of childbearing age, the prevalence rate is higher at 5.5 per 100,000 [2][3][4][5].The incidence of IIH has increased due to the rapid increase of obesity and the estimated total cost of IIH in the USA alone has exceeded USD $444 million [6].Although the exact cause of IIH is unknown, several theories have been postulated, including increased abdominal pressure, sleep apnea syndrome, reduction in cerebrospinal fluid (CSF) outflow or elevated venous sinus pressure [7][8][9].The predominant symptom of IIH is headache, which can vary in intensity from mild to severe [10,11] and chronic headache has been shown to significantly impact the quality of life of individuals with IIH [12,13].Other symptoms of IIH include tinnitus, visual obscuration, and diplopia [1,10,14,15].The accepted criteria for diagnosis of IIH includes the combination of raised ICP without hydrocephalus or mass lesions, normal CSF composition, and normal neuroimaging [13].There are currently no evidence-based guidelines for the medical and surgical management of IIH due to a lack of information on the efficacy of treatments and possible side effects [16,17].
Chronic elevated ICP can lead to cerebral ischemia, cerebral edema, herniation, irreversible brain damage and in severe cases, death [18].Hence, the precise measurement and continuous monitoring of ICP are crucial in caring for patients with IIH [19].ICP can be accurately assessed using lumbar and transcranial methods but are invasive and carry an increased risk of bleeding and infection [20,21].Several non-invasive methods such as magnetic resonance imaging, computerized axial tomography imaging, transcranial doppler ultrasonography, tympanic membrane displacement, and ocular ultrasound have also been used to monitor the ICP changes in patients with raised IIH.However, these methods have limitations such as low sensitivity and specificity, poor inter-rater reliability, and poor test predictability [22].Therefore, more accurate and reliable biomarkers are needed to evaluate the disease state.
Optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) are imaging modalities that provides qualitative and quantitative evaluation of the changes in the retinal nerve fibre layer (RNFL), optic nerve head, macula, and retinal and choroidal perfusion.While OCT can provide structural information about the retina and choroid, OCT-A provides information about the vasculature and blood flow of the retina and choroid (Table 1).OCT/OCT-A are routinely used in ophthalmic clinical settings to diagnose and monitor retinal conditions such as diabetic retinopathy, age-related macular degeneration, and retinal vascular occlusions [23][24][25][26][27][28][29].OCT allows visualization of optic nerve head swelling, changes in the RNFL and retinal pigment epithelium/Bruch's membrane (RPE/BM) layer associated with acute and chronic changes in ICP.In addition, OCT-A allows the evaluation of vessel density on the optic disc and peripapillary region in both newly diagnosed and chronic IIH cases, making these imaging modalities valuable tools for both diagnosing and monitoring IIH [30,31].OCT can be useful to differentiate true disc edema, including papilledema from pseudoedema due to optic disc drusen.Studies have shown that RNFL thickness particularly in the nasal and inferior quadrants were reduced in optic disc drusen compared to optic disc edema [32,33].The standard for evaluating the severity of papilledema is the Frisén scale which grades the optic disc swelling from 0 to 5. Three-dimensional OCT parameters such as optic nerve head volume, height, and shape could potentially offer greater sensitivity compared to the Frisén scale in evaluating treatment outcomes among IIH patients [34].This is because even in IIH patients with normal RNFL thickness, the optic nerve head volume has been shown to be elevated [35].The configuration of the RPE/BM layer in OCT scans can aid in distinguishing papilledema from disc edema caused by other factors like anterior ischemic optic neuropathy (AION).In papilledema, the RPE/BM layer exhibits a U-shape, angled toward the vitreous, whereas in AION and normal individuals, it assumes a V-shaped configuration, angled away from the vitreous [36,37].Increased ICP in IIH can cause biomechanical stress on the optic nerve head and retina resulting in retinal and choroidal folds, and OCT has been shown to be more sensitive than fundus photography is detecting these folds [38].Quantitative assessments of vessel density surrounding the optic nerve head have shown a reduction in disorders such as optic neuritis, arteritic anterior ischemic optic neuropathy (AAION), and optic atrophy [39].As such, the usefulness of OCT-A in diagnosing and monitoring IIH is still unclear.This systematic review examined the current body of literature regarding the utilization of OCT/OCT-A as a biomarker for IIH and reports the most suitable OCT/ OCT-A parameters for the diagnosis and monitoring of IIH.

Methods
This systematic review followed the reporting guidelines outlined in the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and was registered with the International Prospective Register of Systematic Reviews (PROSPER; ID: CRD42024520282).An initial search was performed using Medline and CINAHL to identify relevant articles and keywords.An extensive search strategy was then developed in Medline based on the identified keywords and index terms.The keywords used for the search included: "idiopathic intracranial hypertension", "pseudotumor cerebri", "pseudotumor syndrome", "Nonne's syndrome", "otitis hydrocephalus", "benign intracranial hypertension", "non-infective serous meningitis".The retrieved articles from the Medline search were evaluated to confirm the inclusion of key publications.The search strategy, including the keywords and index terms, were adapted for other bibliographic databases such as PsycINFO (via Ovid SP), Latin American and Caribbean Health Sciences Literature (LILACS) and Scopus (Elsevier) (Online Resource 1).Each database search strategy was run on 17 January 2024.In addition, grey literature sources were searched including the International Standard Randomized Controlled Trial Number (ISRCTN) registry and the International Clinical Trials Registry Platform (ICTRP).There were no limits applied to language, but studies were excluded if they were solely animal studies, case report/case series, editorials, reviews, or conference abstracts.The primary outcome was to report the retinal and optic nerve head changes using OCT/OCT-A in IIH patients.Two authors (MPS and    Any discrepancies in the screening were resolved by mutual consensus between the authors.Reasons for exclusion of the studies were reported in each step of the review process.Included studies were assessed for quality according to the National Institutes of Health Quality Assessment Tool for observational cohort, case-control, cross-sectional, before-after studies with no control groups and controlled intervention studies.The assessment of case-control and before-after studies included 12 items scored as "yes", "no", or "other" (cannot determine, not applicable, not reported).The assessment of cohort, observational, and controlled intervention studies included 14 items that were again scored as "yes", "no" or "other" (cannot determine, not applicable, not reported).

Results
Our initial search yielded 852 articles.Upon reviewing titles and abstracts, 718 articles were excluded (Fig. 1).After examining the full text of the remaining articles, an additional 50 were excluded.The final review comprised 84 articles that utilized ocular imaging as a biomarker for IIH (Table 2).We categorized the included articles into two groups: (1) studies employing OCT as the imaging technique in IIH, and (2) studies employing OCT-A as the imaging technique in IIH.The assessment of the risk of bias of the studies included in this review is shown in Online Resource 2.

OCT & OCT-A PLEX Elite
There was a decreased peripapillary capillary density without changes in capillary flux intensity (CFI) in eyes with papilledema.There were a positive association between the CFI and the RNFL and a negative association between the capillary perfusion density (CPD) and the RNFL subjects had higher RNFL thickness compared to those with IIH, while another study found no significant difference in RNFL thickness between IIH patients and controls [81,90].In addition, it was observed that that IIH patients had initially thicker RNFL measurements, which gradually decreased over subsequent follow-up periods at 1, 3, 6, and 12 months [34,40,66,67].Among the IIH patients, those with severe papilledema were shown to have thicker RNFL than in patients with normal optic discs/minimally or moderately raised discs [41].Patients with recurrent IIH and those without recurrence of IIH were found to have significantly different RNFL thicknesses, with the recurrence group reported to have thicker neural tissue [91].Similarly, RNFL was greater in papilledema than in pseudopapilledema patients [54].However, the RNFL thickness did not differ between the symptomatic and asymptomatic groups [85].Compared to healthy controls, patients with chronic and atrophic papilledema had significantly thinner RNFL thickness [102].In OCT imaging, ppRPE/BM is seen as a well-defined layer above the choroid in the outer retina.It is V-shaped and angled away from the vitreous in normal individuals (Fig. 4).However, in IIH patients with raised ICP, it is U-shaped and angled toward the vitreous (Fig. 5) [36,98].Interventions aimed at lowering the CSF pressure such as lumbar puncture and CSF shunt have demonstrated an ability to transform the ppRPE/BM layer from a U-shaped configuration to the more typical V-shaped configuration [19,30,36].Few studies used a custom segmentation algorithm to develop 3D parameters such as optic nerve head volume and optic nerve head height to compare the optic nerve head changes between IIH patients and controls.They showed that the optic nerve head volume and optic nerve head height were increased in IIH patients than in controls [35,103].In addition, optic nerve head volume was used to differentiate between controls, treated, and untreated patients with IIH [35].Optic disc area, diameter, rim area, thickness, and Bruch's membrane opening were reported to be thicker in IIH patients compared to controls [69,90].In contrast, individuals with IIH exhibited thinner macular GCC, diminished thickness of the peripapillary choroid, reduced depth of both the anterior and posterior lamina cribrosa surfaces depths, and a decrease in optic cup volume [42,77,81,90,99].OCT imaging was also shown to be sensitive in detecting folds such as peripapillary wrinkles, retinal and choroidal folds in patients with IIH [95].
Studies that investigated the utility of OCT in evaluating treatment outcomes in IIH patients demonstrated a significant improvement in the OCT parameters (RNFL thickness, total retinal thickness, choroidal thickness, optic nerve head volume, rim, and disc area) after interventions such as weight loss, oral acetazolamide, and optic nerve sheath fenestration [45,86,91].Studies that examined the relationship between OCT measurements and clinical parameters showed a significant positive correlation between CSF pressure and various OCT parameters, including RNFL thickness, retinal thickness, macular GCC, optic nerve head volume, optic nerve head height, ppRPE/BM layer and Bruch's membrane opening [35,50,51,59,61,69,86].RNFL thickness showed significant positive correlation with visual acuity, visual field loss, papilledema severity, and the Modified Frisén Scale (MFS grades) from fundus photographs [40,65,77].
In addition, macular GCC thickness was found to be significantly associated with optic disc pallor [81].However, no association was identified between CSF pressure and the shape of the optic nerve head [97].

Studies investigating OCT-A as the imaging modality in IIH
Ten studies explored the applicability of OCT-A as a noninvasive imaging biomarker for IIH.In these studies, OCT-A examinations were primarily done in acute settings of papilledema except two studies in chronic papilledema settings.Most of these studies employed OCT-A to assess the peripapillary vascular density differences between individuals with IIH and control groups.The peripapillary area is a ringshaped zone extending from the optic disc boundary (Fig. 4) [104].Vessel density is defined as the percentage of area occupied by both large vessels and microvasculature in a specific area and is calculated over the entire scan area, as well as in the defined sectors within the scan [105].Capillary flux intensity is defined as the total weighted area of perfused microvascular per unit area and capillary perfusion density is defined as the total area of perfused microvasculature per unit area.
The retinal vascular network is organized into four distinct plexuses: the superficial capillary plexus (SCP), intermediate capillary plexus (IP), deep capillary plexus (DCP), and radial peripapillary capillary plexus (RPC) [106].The central retinal artery supplies blood to the SCP which then anastomoses and creates the IP and the DCP.The SCPs are located with the RNFL, ganglion cell layer, and the inner plexiform layer and the DCPs are located within the outer plexiform layer below the IP.The RCP, however, runs parallel with the nerve fiber layer axons (Fig. 5).
Several studies have investigated the peripapillary vessel density in patients with IIH in comparison to controls.Tuntas et al. found a significant reduction in peripapillary vessel density among IIH patients compared to controls in their study using the AngioVue OCT-A device, which exclusively reported peripapillary vessel density (both global and sectoral).[107] Similarly, Cakir et al., utilizing Topcon imaging, observed a notable decrease in peripapillary vessel density across different retinal capillary plexus (SCP, DCP, and choriocapillaries) in IIH patients compared to controls [108].However, Kaya et al., also using AngioVue reported a significant elevation in peripapillary vessel density in IIH patients compared to controls, offering a contradictory perspective [109].In contrast, Fard et al., employing AngioVue found no significant difference in peripapillary capillary density between papilledema patients and controls [110].Moreover, microvascular densities showed an increase in the nerve fiber layer plexus (NFLP) but a reduction in the SCP and DCP in IIH patients compared to controls using the Svision imaging OCT-A device [111].Chonsui et al.in their study using PLEX Elite device showed a decreased peripapillary capillary density without changes in capillary flux intensity in eyes with papilledema [112].
Wang et al.in their study using AngioVue device showed that NFLP positively correlated with Frisén scores of patients with IIH [111].However, SVP, IP, and DCP inversely correlated with Frisén scores of patients with IIH.Similarly, Pahuja et al. showed a negative correlation between superficial peripapillary retinal vessel perfusion and grades of papilledema using the Angioplex device (reported superficial capillary retinal vessel perfusion, deep retinal vessel perfusion and peripapillary choriocapillary perfusion) [102].Kwapong et al. showed microvascular densities (superficial vascular complex and deep vascular complex) positively correlated with ICP using the Svision OCT-A device [113].Peripapillary capillary vessel density in DCP was significantly reduced in optic disc edema compared to the control group, a condition that can mimic IIH.[108]

Discussion
OCT and OCT-A are non-invasive imaging methods widely used in ophthalmology to provide high-resolution crosssectional images of the retina [114,115].OCT and OCT-A measurements have also shown to be a reliable indicator of neuronal death in various neurological disorders such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, neuromyelitis optica, and spinocerebellar ataxia [116][117][118][119].This systematic review examined existing literature to assess the effectiveness of OCT/OCT-A as a diagnostic and monitoring modality for IIH.The predominant imaging technique in the reviewed studies was OCT, with only ten studies using OCT-A.Among studies using OCT as the imaging modality for IIH patients, the most frequently assessed parameter was RNFL thickness.Conversely, studies employing OCT-A as the imaging modality for IIH patients predominantly focused on peripapillary vessel density.In summary, studies utilizing OCT revealed increased thickness in RNFL, retina, as well as increased measurements in optic nerve head volume, optic nerve head height, optic disc diameter, rim area, and rim thickness.However, studies that used OCT-A as the imaging modality showed conflicting results regarding the peripapillary vessel density.
The RNFL comprises axons originating from retinal ganglion cells that converge from the retina and macular region to form the optic nerve.The RNFL is visualized in OCT images as the inner most retinal layer beneath the internal limiting membrane (Fig. 2).The peripapillary RNFL is measured along a 3 mm diameter circle centered on the optic nerve head and the mean thickness of the upper retinal layer is then presented as the average RNFL thickness (Fig. 6).The increased RNFL thickness reported in individuals with IIH is due to the disruption of the axonal transport and intraneural optic nerve sheath ischemia caused by the elevated CSF pressure in the subarachnoid space surrounding the optic nerve.Conversely, the reported decrease in macular GCC thickness in IIH patients is due to the loss of nerve fibers and retinal ganglion cells resulting from oxidative stress-associated prolonged swelling.The subarachnoid space connected to the optic nerve sheath undergoes structural changes due to alterations in the translaminar pressure gradient (difference between intraocular pressure and CSF pressure).Elevated ICP compresses the retrolaminar optic nerve and peripapillary scleral flange, causing deformation of the ppRPE/BM and adjacent sclera toward the vitreous [120][121][122].Studies in this review have shown that in IIH patients, the configuration of the ppRPE/BM follows a U-shaped pattern around the optic nerve head, transitioning to a V-shape after interventions to lower CSF levels [19].
The earliest finding of raised ICP is optic disc swelling which takes about a week or 10 days to appear.However various diagnostic methods such as MRI, serum hormonal assay, axial length evaluation, pattern electroretinogram (PERG), and visually evoked potential (VEP) tests, can aid in detecting subclinical IIH.Liu et al. demonstrated that patients experiencing pulsatile tinnitus displayed several ocular and intracranial signs of IIH on MRI scans, such as optic nerve sheath enlargement, optic nerve tortuosity, posterior globe flattening, empty Sella, downward displacement of cerebellar tonsils into the foramen magnum, and slit-like lateral ventricles [123].According to a study by Prabhat and colleagues, hormonal abnormalities such as raised prolactin, decreased TSH, and decreased cortisol were found in 37.5% of patients with IIH [124].Moreover, studies have shown that the mean PERG and VEP amplitudes were reduced in IIH patients compared to healthy individuals [125].Madill et al.in their study reported a significant difference in globe shape and axial length between patients with IIH and control subjects [126].
Swelling of the optic disc and increased thickness of the RNFL are not exclusive indicators of IIH or increased ICP because they can also occur in other optic neuropathies like optic neuritis and AION.Nevertheless, various parameters that describe the shape of the optic nerve head, such as, optic nerve head volume, optic nerve cup volume, central optic nerve head thickness, volume of Bruch's membrane opening region, bending energy, minimal rim width of Bruch's membrane opening (BMO-MRW), surface area of BMO-MRW, and area of Bruch's membrane opening, may aid in distinguishing between different optic neuropathies.In a study by Yadav et al., a 3D model of the optic nerve head was constructed using high-resolution OCT volume scans, and it was demonstrated that all of the aforementioned parameters, except for bending energy, exhibited differences between IIH, healthy controls, and optic neuritis [127].Similarly, Kaufhold and colleagues employed volume scans to gauge optic nerve head volume in their study, revealing that 3D parameters such as optic nerve head volume and height could distinguish between IIH patients and controls [35].These parameters were shown to be elevated in IIH patients even when the RNFL showed normal thickness, suggesting that it could serve as a potential marker of treatment efficacy and disease advancement [35].Future studies employing OCT as a diagnostic tool for IIH could utilize the 3D optic nerve head parameters to differentiate IIH for other optic neuropathies such as glaucoma, optic neuritis, and AION.
The central retinal artery and ophthalmic artery traverse through the subarachnoid space and are influenced by changes in ICP [128].Out of ten studies utilizing OCT-A as an imaging modality in IIH, five revealed a decrease in peripapillary vessel density [107,108,[111][112][113], one demonstrated an increase in vessel density [109], and one found no disparity in vessel density between IIH patients and controls [110].The decrease in vessel density seen in OCT-A can be due to mechanical compression of the capillary network caused by elevated ICP [129] or due to artifacts arising from the shadowing effect of fluid in papilledema artificially leading to decreased capillary density [129,130].Reduction in capillary vessel density has also been reported in other acute and chronic optic neuropathies such as optic neuritis, Leber's hereditary optic neuropathy (LHON), optic atrophy and non-arteritic anterior ischemic optic neuropathy (NAION) [39].In cases of optic neuritis and dominant optic atrophy, the decrease in vessel density may result from reduced metabolic demands caused by neuronal degeneration and the atrophy of the peripapillary RNFL and GC-IPL, which subsequently reduces blood flow through autoregulatory mechanisms [131].However, LHON is a peripapillary microangiopathy that affects the endothelial and smooth muscle components of the blood vessel walls causing a significant reduction in the peripapillary capillary density [132].In NAION, ischemic alterations due to dysfunctional vascular autoregulation may lead to the destruction of the capillaries [39].
The OCT parameters such as RNFL thickness, macular GCC thickness, rim area, disc area, and cup volume are easily obtained through device software (Figs. 6 and 7).However, certain parameters like optic nerve head volume, optic nerve head height, optic nerve head shape, peripapillary Bruch's membrane angle, anterior laminar surface depth, posterior laminar surface depth, and Bruch's membrane opening require manual calculation using custom segmentation algorithms.Most OCT devices do not automatically provide these measures, limiting their practicality in routine clinical use.In addition, accurately segmenting the outer retinal boundary in the presence of papilledema can be challenging and may lead to inaccuracies [133].Another crucial OCT parameter for distinguishing papilledema in IIH from optic disc edema caused by other factors is the ppRPE/BM shape changes.These changes have shown a correlation with ICP [96].However, the practical application of using ppRPE/BM changes in guiding clinical therapy is hindered by the lack of a commercial method and the need for extensive image processing to identify the RPE/BM boundary beneath an enlarged optic nerve head, limiting the integration of ppRPE/BM changes into clinical decision-making.OCT-A is relatively newer imaging methods offering both Fig. 7 Optical coherence tomography (OCT) imaging test results showing A, macular thickness and B, ganglion cell complex (GCC) thickness structural and blood flow information within the retina and the choroid [134].Given that recent studies using OCT-A in IIH have produced inconsistent findings regarding peripapillary vessel density, future research should concentrate on changes in the perifoveal capillary network.This is because IIH is linked to reduced blood flow in the ophthalmic and central retinal arteries [135].This is the first systematic review to explore studies utilizing ocular imaging as a biomarker for IIH.One of the strengths is that it included 84 studies that used either OCT or OCT-A as the imaging modality in IIH patients.In addition, this systematic review employed study quality assessment tools to appraise the quality of the included studies.There were some limitations in the study.Most of the studies included in this review were case-control studies, with only two randomized control trials.This is because most studies focused on comparing the retinal and optic nerve head changes between IIH patients and healthy controls, thus adopting a case-control design.Another limitation of the study was that it only reviewed various OCT/OCT-A parameters in IIH and could not perform a meta-analysis of these common parameters.This initial step was necessary to understand the current studies and their reporting methods, which will facilitate future meta-analyses.Moreover, conducting a meta-analysis was not possible at this stage given the following reasons: (1) the studies had significantly different designs, methods, and levels of rigor, it might be inappropriate or misleading to statistically combine their results, (2) the outcomes were reported in diverse ways, making it difficult to aggregate the results meaningfully, and (3) some studies lacked sufficient data points for a robust meta-analysis, and some were of low quality or had a high risk of bias, which could lead to misleading conclusions if combined.A narrative approach allows for a more nuanced discussion of the quality and implications of each study.Finally, the specific research question or objective of the review was thought to be better addressed through a narrative synthesis, particularly because the question is broad or exploratory in nature.Another limitation was that our review comprised just ten studies examining the utility of OCT-A in individuals with IIH.This limited number of studies may be attributed to the fact that OCT-A is a relatively recent technology, and its effectiveness in a systemic condition like IIH has yet been firmly established.
To conclude, several OCT parameters have been demonstrated to be different in IIH patients compared to controls and retinal imaging may be useful as an efficient, non-invasive, and affordable biomarker for IIH patients.
of optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) imaging techniques Optical coherence tomography (OCT) Optical coherence tomography angiography (OCT-A) Key components It is a three-dimensional technique Optical coherence tomography uses infrared light directed toward the tissue under examination.The reflected light waves are then analyzed for time delay and differences in signal strength, which allows for assessment of tissue depth and imaging at the selected location The axial resolution of various OCTs is between 5 and 20 μm in the tissue It is a three-dimensional technique Optical coherence tomography angiography uses low coherence interferometry with a focus on motion contrast of red blood cells for vascular imaging.The differences in the reflected OCT signal strength from consecutive OCT B-scans captured at the same location are used to generate an image of the blood flow The resolution of the instrument is 5-10 μm in the axial direction and ∼20 μm in the transverse direction Strengths Cross-sectional retinal imaging providing detailed imaging of the retinal, choroidal, and optic nerve head structure Rapid image generation, with processing completed in seconds Non-invasive Portable Detailed imaging of the retinal, choroidal, and optic nerve head vasculature and perfusion Quantitative imaging on vascular density and perfusion Rapid image generation, with processing completed in seconds Enables imaging of the retinal vascular flow without the need for injection of a dye Non-invasive Portable Limitations Inability to image blood flow Motion artifacts during imaging can lower the quality of the image It lacks the ability to show vascular leakage Small field of view Presence of artifacts can hinder accurate interpretation of the image Image JE) independently evaluated the titles and abstracts and then full-text reports for relevance utilizing Covidence (IBM, Detroit USA).

Fig. 1
Fig. 1 Flow diagram of the systematic literature review search

Fig. 2 Fig. 3 Fig. 4 AFig. 5
Fig. 2 Optical coherence tomography (OCT) image of the retina showing the different layers.ILM inner limiting membrane; RNFL retinal nerve fiber layer; GCL ganglion cell layer; INL inner nuclear layer; IPL inner plexiform layer; ONL outer nuclear layer; OPL outer plexiform layer; ELM external limiting membrane; RPE retinal pigment epithelium.Macular thickness = distance between ILM and RPE; retinal thickness = distance between ILM and photoreceptor layer; choroidal thickness = distance between the outer border of RPE and choroidoscleral surface

Fig. 6
Fig. 6 Optical coherence tomography (OCT) test results showing optic nerve head (ONH) and retinal nerve fibre layer (RFNL) thickness of right (OD) and left eye (OS)

Table
Comparison

Table 2
Summary of the studies included in the systematic review