Retinal Architecture in Parkinson’s Disease with Rapid Eye Movement Sleep Behaviour Disorder: Insights from a Scoping Review

Abstract

Background

Parkinson’s disease (PD) is the leading age-related neurodegenerative disorder with a deposition of α-synuclein-containing Lewy bodies. Idiopathic REM sleep behaviour disorder (iRBD) can occur a decade prior to motor symptoms onset in PD. The retina acts as a window to the brain and its structural changes, along with RBD, may serve as a prodromal marker for PD.

Summary

We evaluated the existing scientific evidence on structural retinal alterations in subjects with iRBD and PD with and without RBD. The selected four studies were observational and investigated the structural retinal layer thickness in iRBD patients, PD patients who likely had RBD (probable RBD), PD lacking RBD, and healthy individuals. Findings reported thinning of the retinal ganglion cell layer, nerve fibre layer (RNFL), outer and inner plexiform layers, inner and outer nuclear layers, reduced ganglion cell complex thickness, and peripapillary RNFL. Additionally, one study reported functional changes, including diminished contrast sensitivity and visual acuity in both the iRBD and PD groups.

Key Message

This scoping review highlights significant thinning of retinal layers in RBD subjects in the context of PD. Retinal imaging serves as a biomarker in the early detection of neurodegeneration.

Keywords

Parkinson’s disease rapid eye movement sleep behaviour disorder retina optical coherence tomography

Introduction

Parkinson’s disease (PD) is an accelerating neurodegenerative disorder that predominantly affects individuals aged over 60 years and has a higher prevalence in males.¹ A meta-analysis from 1990 to 2023 estimates the global prevalence of PD at approximately 151 in 100,000 population.² PD exhibits multiple clinical manifestations affecting motor and non-motor functions. Non-motor symptoms include autonomic dysfunction, such as gastrointestinal issues, like constipation, neuropsychiatric illness, cognitive impairment, circadian rhythm disruptions, hyposmia and sleep disturbances (SD), such as insomnia, excessive daytime sleepiness and rapid eye movement (REM) sleep behaviour disorder (RBD).^3–7 Among the SD, RBD symptoms often occur before the clinical manifestation of α-synucleinopathies (ASP) such as PD, multiple system atrophy or diffuse Lewy body dementia.^{8, 9} Characterised as a parasomnia, RBD involves nocturnal vocalisations, acting out dreams, shouting, kicking, punching and even causing injury to oneself or a bed partner during sleep.^{10, 11} RBD is more frequent in older adults aged over 50 years.¹² The pathophysiology of RBD involves key brainstem regions, specifically the sublaterodorsal tegmental nucleus (SLD) and the precoeruleus region, which regulate REM sleep, as established in the rodent model.¹³ Clinical case reports have also shown that a pontine lesion can result in RBD. Hence, the pons is critical in sleep regulation.¹⁴

The International Classification of Sleep Disorders, 3rd edition criteria, based on polysomnographic findings, state that during REM sleep, muscle tone is minimal.¹⁵ The annual phenoconversion rate from idiopathic RBD (iRBD) to ASP is 6.3% per year.¹⁶ RBD can also manifest after PD diagnosis.^{9, 17} The pooled prevalence rate of RBD is nearly 46% in patients with PD of older age.¹⁸

Furthermore, structural changes in the retina can manifest as prodromal symptoms and precede the motor manifestations of PD. Animal models suggest that melanopsin-containing retinal ganglion cells (RGCs) perceive environmental cues, known as zeitgebers, and transmit this information through the retinohypothalamic tract to the master regulator of circadian rhythms, the suprachiasmatic nucleus.¹⁹ In 1975, Aschoff et al. demonstrated that the synchronised internal circadian system follows the zeitgeber shift.²⁰ The temporal synchronisation of internal clocks with key zeitgebers, such as light, food and physical activity, regulates sleep and rest-activity rhythms.²¹ Consequently, the retina may act as a critical mediator in sleep regulation.

Numerous studies have documented structural retinal changes in patients with PD, suggesting that an interlink exists between neurodegeneration and retinal pathology.^22–29 Supporting this, animal studies have demonstrated retinal abnormalities associated with ASP,^{30, 31} which are consistent with the pathology observed in human post-mortem enucleated eyes from patients with ASP.³² Notably, Pérez-Acuña et al.’s study showed that intravitreal injection of α-synuclein preformed fibrils into the eyes of mice results in the deposition of α-synuclein aggregates in both the retina and brain along the visual pathway,³¹ and leads to impaired vision.³³ Previous evidence suggests that neurodegenerative processes may occur concurrently in the retina and the brain, with retinal alterations serving as early markers of PD. Based on the available scientific evidence, we hypothesise that the coexistence of RBD and retinal abnormalities in an individual may further increase the risk of developing PD. Therefore, both RBD and retinal changes are considered potential early indicators of neurodegenerative disease, offering an opportunity for timely detection and intervention.

Methods

The scoping review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines.

Search Methodology

We comprehensively and systematically searched electronic databases, including MEDLINE, to retrieve suitable articles up to June 2025, utilising MeSH terms: PD, RBD, optical coherence tomography (OCT) and retina. Figure 1 illustrates the combination of keywords used in retrieving an appropriate article suitable for the review. The authors, M.S.N. and P.M., independently screened the research studies for titles and abstracts. The study selection inclusion criteria included those studies for analysis if they were (a) peer-reviewed original research articles and (b) full-text articles available in the English language.

Figure 1.

Note: OCT: Optical coherence tomography; PD: Parkinson’s disease; RBD: REM sleep behaviour disorder.

The exclusion criteria included: (a) presence of other movement disorders, like atypical parkinsonism or neurological co-morbidities; (b) sleep disorders like insomnia and excess daytime sleepiness; and (c) ocular diseases like glaucoma. To minimise the risk of bias, two authors searched the relevant articles independently, and they made a joint decision in the event of any conflicts.

Study Extraction

We retrieved the following information from each selected study: author, publication year, number of study participants, type of OCT device used, study cohorts, cohort sample sizes, retinal structures and findings, as tabulated in Table 1.

Table 1.

Retinal Structural Changes Among Patients with iRBD, PD With and Without RBD and Healthy Controls.

Author	Number of Participants	Type of OCT Device Used	Retinal Layers Across Cohorts			Findings
Rascunà et al.³⁴	PD: n = 21; iRBD: n = 19; HCs: n = 17;	Cirrus HD-OCT SD angiography OCT-A	Significant thinning in RNFL, GCL, INL, OPL, ONL, pRNFL in iRBD versus HCs.	Significant thinning in RNFL, GCL, OPL, ONL, pRNFL: PD versus iRBD.	Significant thinning in RNFL, GCL, INL, OPL, ONL, pRNFL: PD versus HCs.	Significant retinal layer thinning in PD < iRBD versus HCs (p < .001). Positive correlation: retinal thinning b/w impaired visual acuity/colour vision.
Whitfield et al.³⁵	PD + RBD: n = 11; iRBD: n = 12; HCs: n = 28;	Zeiss SD-OCT	NS differences in GCL, IPL, RNFL in iRBD versus HCs.	NS differences in GCL, IPL, RNFL: iRBD versus PD + RBD.	NS difference in GCL, IPL, RNFL: PD versus HCs.	CSVA significantly reduced: PD + RBD < iRBD < HCs (p < .05). 3/12 (25%) iRBD developed parkinsonian symptoms + ↑UPDRS on follow-up.
Lee et al.³⁶	PD: n = 49; iRBD: n = 21; HCs: n = 54;	Spectralis SD-OCT	GCC thickness: ↓ Inner temporal and inner inferior sectors in iRBD versus HCs.	NS difference in GCC between dnPD versus iRBD.	GCC thickness ↓ outer temporal, outer nasal, inner temporal, inner inferior sectors in dnPD versus HCs.	Significant GCC thinning: dnPD < iRBD < HCs (p < .05). Significant WRT thinning: dnPD < HCs (p < .05). Reduced striatal DAT uptake correlates with retinal thinning in iRBD.
Yang et al.³⁷	PD: n = 63; iRBD: n = 14; HCs: n = 26;	HD-OCT (Zeiss)	pRNFL: ↓ Average and superior quadrants in iRBD versus HCs.	pRNFL: Reduced in the average and inferior quadrants in PD + pRBD versus PD-pRBD.	pRNF: ↓ Average and inferior quadrants in PD + pRBD versus HCs. pRNFL: ↓ Inferior quadrant in PDND versus HCs.	Significantly reduced pRNFL in RBD (iRBD/PD + pRBD) versus non-RBD (PD-pRBD/HCs) (p < .0001). RBD (iRBD/PD + RBD) is associated with pRNFL thinning; retinal changes worsen with disease progression.

Note: b/w: Between; CSVA: Contrast sensitivity visual acuity; DAT scan: Dopamine transporter scan; dnPD: Drug-naïve PD; GCC: Ganglion cell complex; GCL: Ganglion cell layer; HCs: Healthy controls; HD-OCT: High definition OCT; INL: Inner nuclear layer; IPL: Inner plexiform layer; iRBD: Idiopathic RBD; NS: Not significant; OCT: Optical coherence tomography; ONL: Outer nuclear layer; OPL: Outer plexiform layer; PD: Parkinson’s disease; PDND: Newly diagnosed PD; PD + pRBD: PD with probable RBD; PD-pRBD: PD without probable RBD; pRNFL: Peripapillary RNFL; RBD: REM sleep behaviour disorder; RNFL: Retinal nerve fibre layer; SD angiography OCT-A: Spectral domain optical coherence tomography angiography; SD-OCT: Spectral domain OCT; UPDRS: Unified Parkinson’s Disease Rating Scale; WRT: Whole retinal thickness; ↓: Decreased; ↑: Increased.

We retrieved 19 articles from the MEDLINE database using a fusion of MeSH keywords. After removing 11 duplicate records and one conference proceeding, seven unique articles were screened in accordance with the PRISMA-ScR guidelines, as illustrated in Figure 2. Of these, we excluded three articles: one reported on Gaucher’s disease, another discussed a biomarker for cognition, and the third was a review article with a meta-analysis.

Figure 2.

The Flowchart Depicts the Selection of Articles According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) Guidelines.

Quality Review

We evaluated the quality of the selected research articles using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist and the Newcastle–Ottawa Quality Assessment Scale (NOS), which apply to observational studies, including case-control and cohort studies. The STROBE checklist comprises 22 items, designed for standard reporting of observational studies. At the same time, NOS consists of three domains: (a) selection, (b) comparability and (c) exposure, which capture the quality assessment of case-control studies. Table 2 summarises the article quality assessment based on the STROBE criteria, while Table 3 presents the evaluation results using the NOS checklist.

Table 2.

Represents the Paper Quality Using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist.

Grouped Items	STROBE Components	Rascunà et al.³⁴	Whitfield et al.³⁵	Lee et al.³⁶	Yang et al.³⁷
Items 1 and 2	Title and abstract; background/rationale	Yes	Yes	Yes	Yes
Items 3–8	Objectives; study design; setting; participants (cohort/cross-sectional); variables; data sources/measurement	Yes	Yes	Yes	Yes
Item 9	Bias	No	No	No	Yes
Items 10–12	Study size; quantitative variables; statistical methods (cohort/cross-sectional)	Partial	Partial	Yes	Yes
Items 13–17	Participants; descriptive data; outcome data; main results; other analyses	Yes	Partial	Yes	Yes
Items 18–22	Key results; limitations; interpretation; generalisability; funding	Yes	Yes	Yes	Yes
	STROBE quality check	Good	Good	Good	Good

Note: No: Not reported; Partial: Not adequately reported; Yes: Adequately reported.

Table 3.

Evaluates the Paper Quality Using the Newcastle–Ottawa Quality Assessment Scale (NOS) Tool.

Grouped Items	NOS Case-control Study	Rascunà et al.³⁴	Whitfield et al.³⁵	Lee et al.³⁶	Yang et al.³⁷
A	Selection
1234	Adequacy of case definition Representativeness of cases Selection of controls Definition of controls Total	*–3*	***4	***4	**–3
B	Comparability
12	Study controls for age Study controls for other confounding factors Total	*2	–1	*2	*2
C	Exposure
123	Ascertainment of exposure Same method of ascertainment for cases and controls Non-response rate Total	**3	**3	**3	**3
	NOS quality check	High	High	High	High

Note: Scoring: *Item fulfils the criteria. Score 7–9: High quality. Score 4–6: Moderate quality. Score 0–3: Low quality.

Study Participants and Sample Sizes

Sample sizes in the respective studies are as follows: Rascunà et al. studied patients with PD (n = 21), iRBD (n = 19) and healthy controls (HCs) (n = 17).³⁴ Whitfield et al. included patients with PD + RBD (n = 11), iRBD (n = 12) and healthy cohorts (n = 28).³⁵ Lee et al.’s study involved patients with PD (n = 49), iRBD (n = 21) and healthy individuals (n = 54).³⁶ Yang et al. recruited patients with PD (n = 63), iRBD (n = 14) and HCs (n = 26).³⁷ All the studies utilised OCT imaging to assess the retinal structures.^34–37

Results

Four clinical studies satisfied the predetermined inclusion criteria for this scoping review. The selected research articles met the requirements of both the STROBE and NOS checklists, and the authors rated them as high-quality publications. Table 1 provides the core findings of the selected studies.

Retinal Structural Changes

Three studies investigated structural alterations in the macular retinal layers.^34–36 Rascunà et al. found a significant reduction in macular retinal nerve fibre layer (RNFL) thickness in patients with PD against iRBD subjects (p < .001).³⁴ Additionally, Rascunà et al. noted a substantial reduction in RNFL thickness in iRBD subjects compared to HCs (p < .001).³⁴ Conversely, Whitfield et al. found no significant difference in RNFL thickness between PD patients with RBD and those with iRBD.³⁵ Rascunà et al. also found a considerable thinning of the ganglion cell layer (GCL) in PD compared with iRBD, and in iRBD in comparison with HCs (p < .001).³⁴ Lee et al. studied the ganglion cell complex (GCC).³⁶ The authors found significantly reduced thickness across outer temporal, outer nasal, inner temporal and inner inferior sectors of the drug-naïve PD (dnPD) group relative to HCs (p < .05).³⁶ Lee et al. also observed thinning in the inner temporal and inner inferior sectors of the GCC in patients with iRBD versus HCs (p < .05).³⁶

In addition to the RNFL and GCL layers, the authors studied other macular layers. Rascunà et al. observed significant thinning of the inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL) in iRBD subjects when compared with HCs.³⁴ While Whitfield et al. found no notable differences.³⁵ Lee et al. and Yang et al. did not study the other macular retinal layers.^{36, 37}

Notably, Rascunà et al. found significant thinning in the peripapillary RNFL (pRNFL) across the three groups (PD, iRBD and HCs) (p < .001).³⁴ Similarly, Yang et al. reported profound thinning of the pRNFL in the average, superior sector of iRBD patients and in the average, inferior sector of PD + PD with probable RBD (pRBD) patients relative to HCs (p < .001).³⁷ In addition, Yang et al. observed reduced pRNFL thickness in the average and inferior quadrants between PD + pRBD and PD-pRBD (p < .05).³⁷ Apart from macular retinal layers, one study reported thinning in the inner superior, outer and inner temporal, as well as the inner inferior sectors of the whole retina in dnPD patients, in contrast to HCs (p < .05).³⁶

Functional Changes

Beyond structural changes, Whitfield et al. observed functional changes, with significantly reduced contrast sensitivity visual acuity (CSVA) in subjects with PD and RBD compared with those with iRBD, and iRBD versus HCs.³⁵ The authors, upon a 1-year follow-up, reported a significant decline in CSVA scores (n = 12; 6 PD + RBD and 6 iRBD).³⁵

Lee et al. performed dopamine active transporter (DaT) imaging in study subjects. They found a significant reduction in tracer uptake in the bilateral caudate and left anterior putamen among the iRBD and dnPD groups, distinct from HCs (p < .001).³⁶ In patients with iRBD, tracer absorption was markedly reduced in the right anterior and bilateral posterior putamen (p < .001), differing from HCs.³⁶

Discussion

The key findings of our scoping review, based on scientific studies, include: (a) patients with RBD exhibit thinner RNFL in the context of PD.^{34, 35} (b) Functional visual changes may precede structural retinal changes in subjects with RBD.³⁵ (c) The parafoveal GCC thinning may occur upon the initial presentation of ASP, in iRBD and dnPD patients.³⁶ (d) A potential relationship exists between retinal changes and dopaminergic innervation of the striatum, highlighting a parallel degeneration in the retina and brain.³⁶

To our knowledge, the literature is scarce on retinal changes in individuals with RBD in relation to ASP.^34–37 The first scoping review aims to explore the retinal changes in subjects with iRBD and those with PD associated with RBD. Rascunà et al. reported RNFL thinning in both PD and iRBD subjects,³⁴ whereas Whitfield et al. found no significant changes in RNFL thickness in PD with RBD and iRBD subjects.³⁵ The discrepancies in findings might be due to differences in sample size, disease severity and OCT instruments. Rascunà et al. used Cirrus OCT,³⁴ and Whitfield et al. used Zeiss OCT,³⁴ for retinal imaging. Moreover, Rascunà et al. did not specify RBD status in PD subjects,³⁴ while Whitfield et al.’s study involved iRBD and PD with RBD subjects.³⁵

Zhou et al. identified an association between the thinning of the GCL part of the ganglion cell-inner plexiform layer (GCIPL) complex and an increased risk of RBD.³⁸ Evidence on GCC and GCL thinning is consistent.^{34, 36} Rascunà et al. and Lee et al. found reduced GCL and GCC thickness in iRBD, dnPD and PD cohorts compared to HCs.^{34, 36} Conversely, Whitfield et al. found functional changes, such as reduced CSVA, in both iRBD and PD with RBD groups, and no notable difference in GCL thickness between the iRBD and PD with RBD groups versus HCs.³⁵

Although study results vary, three out of four studies demonstrate RNFL, GCL and GCC thinning in iRBD and PD cohorts, establishing these structural retinal changes as robust biomarkers for early α-synucleinopathy.^{34, 36, 37} Whitfield et al. uniquely identified early functional CSVA deficits without any structural alterations,³⁵ likely reflects that functional loss precedes structural degeneration. As the disease progresses, retinal structural thinning provides reliable and quantifiable evidence of neurodegeneration. These findings position both structural and functional changes in the retina as complementary biomarkers for early PD detection.^34–36

Despite varied findings, the above studies indicate that there could be a presence of underlying shared neurodegenerative pathology between iRBD and PD with RBD. Notably, Lee et al. demonstrated correlations between GCC thinning and dopamine loss in the striatum (both motor and cognitive regions) among patients diagnosed with iRBD and newly diagnosed dnPD groups, relative to the healthy group.³⁶ Nguyen-Legros observed decreased dopaminergic innervation in the retinal system of parkinsonian patients.³⁹ These results reinforce the concept of a parallel, global loss of dopamine in both the retina and the brain.^{36, 39}

Further supporting the concept of concurrent loss of dopamine in the retina and brain, a study conducted by Ortuño-Lizarán et al. examined melanopsin-containing RGCs in donor eyes from PD patients and found significant reductions in cell number and dendritic branching.⁴⁰ Since RGCs project into the brain’s circadian centres, regulating the circadian rhythm, such degeneration may also contribute to sleep and circadian disturbances in PD.⁴⁰ Taken together, reduced GCL, GCIPL or GCC thickness could serve as an emerging biomarker for prodromal ASP in individuals with RBD.

Nishikawa et al. further supported the connection between retinal and striatal neurodegeneration by reporting reduced DaT tracer uptake in 29 subjects with iRBD, who met the prodromal PD diagnostic criteria.^{41, 42} At the molecular level, a possible mechanism for changes in retinal structure may involve phosphorylated α-synuclein deposits, which could trigger microglial activation and neuroinflammation, contributing to structural changes.^{43, 44} Moreover, Bodis-Wollner et al. report the presence of α-synuclein deposition in the retinal ganglionic cells in post-mortem eyes of patients with PD.⁴⁵ α-synuclein deposits can contribute to the altered visual processing and retinal morphological changes in PD, implicating retinal involvement in PD pathology.⁴⁵

Several studies have reported thinning of pRNFL in patients with PD.^{26, 34, 37, 46} Ma et al. identified that the patients with PD showed a distinct pattern of altered pRNFL, showing significantly reduced thickness in the nasal and inferotemporal sectors relative to HCs.⁴⁷ Similarly, studies by Yang et al. and Rascunà et al. demonstrated reduced pRNFL in different sectors.^{34, 37} The findings suggest the preferential involvement of pRNFL in PD manifestation.

Furthermore, Whitfield et al. observed three patients with iRBD who developed parkinsonian symptoms upon a 1-year follow-up, as observed by increased Unified Parkinson’s Disease Rating Scale (UPDRS) scores.³⁵ Another study by Zhou et al., using a Mendelian randomisation approach, found no significant link between genetically predicted pRNFL thickness and motor severity, although they reported reduced UPDRS scores.³⁸ Nevertheless, Yang et al. studied pRNFL and motor severity using UPDRS in patients with PD + RBD and PD without RBD, and found no significant association between pRNFL thickness and motor severity.³⁷

Zhou et al.’s study was excluded from our review, as it did not involve imaging-based retinal measurements or directly compare PD patients with and without RBD.³⁸ The studies by Zhou et al. and Whitfield et al. employed different methodological approaches: Zhou et al. explored the genetic predisposition to retinal thinning, whereas Whitfield et al. studied retinal thinning in the context of prodromal PD-related pathological changes.^{35, 38} Collectively, these findings suggest that, whether retinal thinning is genetically predisposed or acquired through disease progression, it is not associated with motor symptom severity in PD.³⁸

In addition to structural changes in the retina, the authors also investigated possible functional visual impairment in subjects with RBD.^{35, 36} Marques et al. assessed visuoperceptive function using contrast sensitivity testing in patients with PD, with and without RBD, and in the iRBD group.⁴⁸ The authors found no appreciable differences among the PD + RBD, PD-RBD and iRBD groups.⁴⁸ Similarly, Whitfield et al. and Lee et al. reported no significant differences in CSVA scores between patients with PD + RBD, dnPD and iRBD.^{35, 36} A plausible reason for these similar findings is the comparable functional deficits in the underlying shared mechanism, such as early dopaminergic lateral inhibition.^49–51

Foundational studies support the concept of dopaminergic lateral inhibition.^49–51 In 1956, Hartline et al. described the mechanism of lateral inhibition in the Limulus eye, in which stimulation of one photoreceptor suppressed the activity of the neighbouring photoreceptors, thereby enhancing contrast in visual perception.⁵¹ Later, Kelly demonstrated the relevance of lateral inhibition in human colour perception.⁵² Extrapolating from these findings, we infer that early impairment of dopaminergic lateral inhibition may contribute to visual dysfunction in PD and iRBD, particularly deficits in CSVA. Given that iRBD can be a part of the prodromal phase of PD, such impairments may reflect a shared early neurodegenerative mechanism.³⁵

Supporting the body-first hypothesis, iRBD, anxiety, depression, constipation and anosmia can manifest prodromally.^{53, 54} In contrast, the brain-first subtype of PD with RBD negative showed primary loss of dopamine in the brain.⁵⁵ Similarly, Nishikawa et al. reported that 95% of iRBD cases displayed a body-first phenotype, suggesting a more widespread systemic distribution of α-synuclein pathology rather than brainstem confinement.⁴¹ In addition, as the retina is an extension of the embryonic ectoderm, early retinal changes detected by OCT in iRBD subjects could serve as an important marker of α-synucleinopathy. Moreover, Lee et al. found reduced tracer uptake in iRBD and dnPD subjects with reduced GCC thickness.³⁶ Taken together, this review suggests that the retinal changes are integral to the iRBD phenotype and support the body-first hypothesis, which contributes to synucleinopathies, as schematically represented in Figure 3. Furthermore, retinal changes, such as RNFL or GCC thinning, serve as a biomarker that reflects the parallel neurodegenerative process in the brain, as illustrated in Figure 3. Hence, OCT is a valuable, non-invasive biomarker for neurodegeneration in iRBD.

Figure 3.

Note: GCC: Ganglion cell complex; GCL: Ganglion cell layer; INL: Inner nuclear layer; IPL: Inner plexiform layer; LC: Locus coeruleus; OCT: Optical coherence tomography; ONL: Outer nuclear layer; OPL: Outer plexiform layer; pRNFL: Peripapillary RNFL; RBD: REM sleep behaviour disorder; RBDSQ: REM sleep behaviour disorder screening questionnaire; RNFL: Retinal nerve fibre layer; SLD: Sublaterodorsal tegmental nucleus.

The limitations of our review are:

The articles searched in the MEDLINE database may have limited the breadth of the review.

Due to the paucity of studies and small sample sizes reported thus far, it is challenging to comprehensively understand the exact pattern of underlying pathology in iRBD in the context of PD-related conditions.

Some included studies relied on probable RBD diagnosis rather than polysomnography-proven RBD, which may add diagnostic inaccuracies.

Conclusion

Our review highlights that patients with RBD exhibit thinner macular RNFL and GCL in the context of PD, along with functional changes such as reduced CSVA. Hence, both structural and functional changes thus complement RBD as biomarkers for early ASP detection in the PD spectrum. GCC, in particular, may identify individuals with iRBD who are at risk of later α-synucleinopathy manifestations. Also, the findings likely support the body-first subtype hypothesis and its role in PD progression. Consequently, a multimodal approach combining non-invasive OCT with other imaging biomarkers holds promise for early detection of dopaminergic neurodegeneration in the retina and the brain. Future longitudinal, multicentre studies warrant the use of retinal biomarkers in iRBD and PD populations.

Footnotes

Authors’ Contribution

M.S.N.: Writing—original draft preparation, data curation and execution. P.M.: Conceptualisation, supervision, manuscript review and critique. M.D.: Manuscript review and critique. P.K.P.: Manuscript review and critique. R.Y.: Conceptualisation, supervision, manuscript review and critique. All authors approved the final version for submission.

Declaration of Conflict of Interests

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Megha Shri Nanjundaswamy gratefully acknowledges the financial support from Council of Scientific and Industrial Research (CSIR) funding with sanction no: 09/0490(16118)/2022-EMR-I and Parkinson’s Disease and Movement Disorders Research Fund (File no: 13020). The funders had no role in the study design and preparation of the manuscript.

Statement of Ethics and Patient Consent

As this scoping review article is based solely on existing published literature, it does not require ethical approval or patient consent from the institution.

ORCID iDs

Megha Shri Nanjundaswamy

Ravi Yadav

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