“Choroidal nevus through a broader vision: Retinal imaging acquisition captured with Broad Line Fundus Imaging technology.”

doi:10.21203/rs.3.rs-1620401/v1

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“Choroidal nevus through a broader vision: Retinal imaging acquisition captured with Broad Line Fundus Imaging technology.”

https://doi.org/10.21203/rs.3.rs-1620401/v1

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Purpose: To describe the peculiarities in imaging acquisition of fourteen patients with choroidal nevus using the Broad Line Fundus Imaging (BLFI) technology.

Study Design: Single-center, retrospective, cross-sectional analysis.

Methods: We retrospectively reviewed the clinical records of 14 patients with choroidal nevus. We analyzed the retinal images by deconstructing them into color channels (Red, Green, and Blue) with broad line fundus imaging technology. The lesions were categorized as detectable or undetectable. Detectability was qualitatively characterized as dark or light following assessment by two experienced ophthalmologists.

Results: We have found that choroidal nevus is undetectable in the blue channel (BC) (435 - 500 nm) and the green channel (GC) (500-585 nm). The only visible changes are related to the drusen, which appeared in BC and GC as light focal dots, correlated to the yellowish foci in the true-color image. On the red channel (RC) (585-640 nm), all lesions revealed the same pattern: a well-defined dark spot, with enhanced contrast, allowing the better visualization, measuring, and characterization of the nevus when compared with the other color channels, including the true-color imaging.

Conclusion: BLFI application in choroidal nevus might be helpful at presentation, refining the diagnostic reliability, and monitoring, as it allows for better detection of alterations in the lesions. The peculiarities of the choroidal nevus are better assessed when using the RC due to its longer wavelength and deeper penetration in the retina and choroid.

Choroidal Nevus

Multimodal Imaging

Broad Line Fundus Imaging

True Color Imaging.

Choroidal nevus is the most common benign intraocular tumor, with overall prevalence ranging from 5–25% in the adult population.[1–6] The term is used to describe a benign tumor composed of “normal or atypical melanocytes derived from the neural crest.”[7] This lesion is typically found incidentally on routine ophthalmic funduscopic examination. Several studies aimed to highlight sentinel signs predictive of malignant transformation, and easily recalled mnemonics were developed, providing resources to the medical society that may optimize patient monitoring and counseling. The mnemonic was updated by Shields et al.[8] to “To Find Small Ocular Melanoma Doing IMaging,” reflecting the paramount role of the current multimodal imaging era. Choroidal nevus is currently evaluated with fundus photography, ultrasonography, fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography (OCTA).[9]

Currently, several devices offer different methods for acquiring retinal images. A recent publication sought to determine the potential use of the red-green channel feature of ultra-wide-field (UWF) imaging in the early detection of a suspicious choroidal naevus or small choroidal melanoma by using a Scanning Laser Ophthalmoscope system. They found two distinct patterns in the vast majority of the patients regarding the red channel (RC) and the green channel (GC): the lesions were dark on RC/undetectable on GC or dark on RC/light on GC. The authors suggest that the RC may be superior to autofluorescence for the follow-up of choroidal nevus due to deeper penetration. However, the study could not correlate with prognostic significance despite novel and promising observations acquired.[10]

By the same token, digital UWF retinal imaging systems powered by Broad Line Fundus Imaging (BLFI) technology enable high-resolution imaging acquisition through sequential illumination of broad-spectrum red, green, and blue light-emitting diodes.[11] The single image can be deconstructed in channels to see the individual wavelength views. The blue channel (BC) (435–500 nm) increases the visibility of anterior retinal layers, the GC (500–585 nm) permits a view from the sensory retina to the retinal pigment epithelium (RPE), and the RC (585–640 nm) and Infrared laser diode (785nm) scans the deeper structures from the RPE to the choroid.

This study aims to enlighten and describe choroidal nevus imaging acquisition peculiarities using the BLFI technology.

A single-center, retrospective, cross-sectional analysis was performed by reviewing the clinical records of 14 patients with choroidal nevus in follow-up at the Leitão Guerra - Oftalmologia, Salvador, Brazil, from September 2021 to December 2021. This 4-months period did not overlap previous investigations on this topic, and no patient in this series was included in any previously published series. The Research Ethics Committee of the Suel Abujamra Institute reviewed and approved this study protocol. This study was conducted in accordance with the tenets of the Declaration of Helsinki, and the reporting of this study conforms to the STROBE statement.

Data were collected regarding patient demographic features, tumor characteristics, visual symptoms, and ocular comorbidities. Each patient underwent a complete ocular examination, including best-corrected visual acuity (BCVA), anterior segment examination, intraocular pressure measurement, dilated fundus examination, FAF, and color fundus photography. FAF, True Color composite images and individual reflectance images (blue, green, red, infrared) were acquired using CLARUS 700 (Carl Zeiss Meditec, Dublin, California, USA). This system utilizes BLFI, a hybrid of confocal scanning laser ophthalmoscopy and traditional fundus photography. It utilizes line scanning illumination with light-emitting diodes and an aperture confocal to the illumination.[12] The UWF images were then reviewed in all of the color channels (red, green, and blue) by adjusting the blend function of the software. The lesions were categorized as detectable or undetectable. Detectability was qualitatively characterized as dark or light following assessment by two experienced ophthalmologists (RLLG and GCSB).

Only patients with complete and good-quality imaging were included in the present study. The diagnosis of choroidal nevus was based on clinical appearance and examination. All the patients were followed-up, at least annually after diagnosis, with imaging documentation to detect changes of the lesions. During each monitoring visit, the patients underwent a complete ophthalmological examination.

A total of 14 eyes from 14 patients presenting choroidal nevus were included. The mean age at diagnosis was 52,7 (± 13,3) years. Seven patients were male, 7 were females, and all were Caucasian. No patient had significant systemic and ocular comorbidities. All the patients were asymptomatic at presentation, with BCVA ⩾20/25, remaining stable until the final follow-up. All the lesions were incidentally discovered during a routine examination. Slit-lamp biomicroscopy, IOP measurement using Goldmann applanation tonometer, and pupillary light reflexes were unremarkable in both eyes of all patients. No significant findings in the fellow eyes were identified. The demographic and clinical characteristics are summarized in Table 1.

Table 1

Demographics and clinical presentation in patients with choroidal nevus.
Patient Number	Eye	Age (years) at diagnosis	Sex	BCVA at presentation	Clinical presentation
#1	Right	69	Male	20/20	Dark, flat, and well-defined lesion in the juxtapapillary region (temporal-superior)
#2	Right	33	Male	20/20	Dark, flat, and well-defined lesion in the inferotemporal arcade.
#3	Left	54	Female	20/25	Dark, flat, and well-defined lesion in the juxtapapillary region (nasal-superior).
#4	Left	24	Female	20/20	Dark, flat, and well-defined lesion with drusens in the temporal-inferior quadrant.
#5	Left	71	Female	20/25	Dark, flat, and well-defined lesion in the superotemporal arcade.
#6	Right	50	Female	20/20	Dark, flat, and well-defined lesion in the inferior quadrant.
#7	Right	56	Male	20/20	Two small lesions (dark, flat, and well-defined), one in the superotemporal arcade and the other in the inferotemporal arcade.
#8	Left	57	Female	20/25	Dark, flat, and well-defined lesion in the nasal-inferior quadrant.
#9	Left	67	Female	20/20	Dark, flat, and well-defined lesion in the inferotemporal arcade.
#10	Right	58	Male	20/20	Dark, flat, and well-defined lesion in the superior quadrant.
#11	Left	41	Male	20/20	Dark, flat, and well-defined lesion in the nasal-superior quadrant.
#12	Left	50	Male	20/25	Dark, flat, and well-defined lesion in the temporal-superior quadrant.
#13	Left	48	Male	20/20	Dark, flat, and well-defined lesion with drusens, in the superior quadrant.
#14	Right	60	Female	20/20	Dark, flat, and well-defined lesion in the superior quadrant.
BCVA: best-corrected visual acuity.

All of the lesions clinically evinced a melanocytic appearing consistent with a flat choroidal nevus showing no overlying subretinal fluid or RPE changes and absence of any other new fundus abnormalities. The overlying vitreous and the surrounding retina were unremarkable in all cases. As peculiarities of the cases and lesions, case #7 revealed two choroidal nevus in the same eye (right eye), one in each temporal arcade, and approximately the same size; cases #4 and #13 presented drusens compounding the choroidal nevus.

In all assessed images (Fig. 1), the choroidal nevus revealed the same behavior. Regarding BC, the lesions were undetectable in every image obtained. The only visible change is related to the drusen present in the choroidal nevus in cases #4 (Fig. 1N) and #13, which appeared in BC as light focal dots, correlated to the yellowish foci in the true-color image. This pattern was maintained in GC and RC, although its contrast was more evident in the GC (Fig. 1O) compared to the other channels.

Lesions were also undetectable in the GC, and it was only possible to detect the presence of drusen as hyperrefringent foci. None of the lesions were categorized as a light spot in the GC, although previous studies have described this behavior when using other image acquisition systems.

In respect of the RC, all the lesions revealed the same pattern, presenting as a well-defined dark spot, with higher contrast levels, allowing the better identification, measuring, and characterization of the nevus when compared with the other color channels, including the true-color imaging. The features of choroidal nevus in each color channel are summarized in Table 2.

Table 2

Choroidal Nevus Features in Each Color Channel.
Color Channel	Features
Blue Channel	Choroidal nevus are undetectable. Drusen appear as low contrast light focal dots.
Green Channel	Choroidal nevus are undetectable. Drusen appear as medium contrast light focal dots.
Red Channel	Choroidal nevus appears as a dark, flat, and well-defined lesion. Drusen appear as low contrast light focal dots.

Our study analyzed choroidal nevus images assessed with the BFLI technology, highlighting the particularities between color channels separately and reinforcing the value of RC in assessing choroidal nevus details. These features may be used to better detect and monitor these lesions, besides providing subsidies for further studies in the area.

Choroidal nevus is the most common primary intraocular tumor.[13] These tumors should be routinely monitored for potential malignant transformation into melanoma,[9] and it is crucial to detect suspicious features at an early stage. The concept of artificial-intelligence-based screening of choroidal nevus has already been raised, and specialists suggest that it would significantly enhance the detection and early treatment of melanoma, with the potential to save lives.[14] Several reports aimed to identify clinical factors[8, 15, 16] and, more recently, multimodal imaging factors that may predict the transformation of nevus into melanoma.[17] A recent study sought to evaluate clinical and multimodal imaging features per millimeter increase in nevus thickness and correlate increasing thickness with a greater risk of growth into melanoma.[18]

The choroidal nevus is generally found incidentally on routine ophthalmic funduscopic examination, and documentation of the lesions is paramount for the better monitoring, counseling, and treatment of the tumors and their complications. With the advent of UWF true-color fundus cameras, a single capture is enough in the great majority of the cases to identify a choroidal nevus and its associated clinical features. In addition, these devices dispose of different technologies for their image acquisition.[19]

To the best of our knowledge, no study aimed to examine features of choroidal nevus using a digital UWF retinal imaging system powered by BLFI technology. Previous studies have been harnessed in assessing choroidal nevus by using a Scanning Laser Ophthalmoscope system with two laser wavelengths.[10, 20] Kernt et al.[20] suggest that the pattern “dark on RC/light on GC” distinctive malignant melanoma. On the other hand, Papastefanou et al. postulate that these devices’ use of red-green channels is not a reliable diagnostic tool in the early detection of small melanomas. The authors also found that RC has the benefit of assessing tumor margins in serial monitoring, but RC and GC patterns are limited in differentiating choroidal nevus from melanomas.

We have found that choroidal nevus is undetectable in BC. This was already expected since this color channel allows for better visibility of anterior retinal layers such as nerve fibers, inner limiting membrane, and vessels.

Concerning the GC, the choroidal nevus was undetectable in all of our cases. None of the lesions of our sample presented as light or bright spots in GC, as previously reported by others studies.[10, 20] We suggest that this observation is related to the different image acquisition modalities, reinforcing the slight disparities between these different systems.

In the RC, all the choroidal nevus turned up as a well-exposed dark spot, with well-defined margins and contrasting with the underlying retina. This pattern is consistent with other studies that used different technologies of imaging acquisition. This information reinforces the role of RC in the better definition and characterization of choroidal nevus, regardless of the imaging acquisition method.

The limitations of our study are the small sample of cases collected for analysis, in addition to the fact that we did not use a comparative population, such as choroidal melanoma. On the other hand, our study provided novel information using an image acquisition method that had not been described in the literature for the proposed condition. As this is a lesion with potential for malignancy in choroidal melanomas, we believe that retinal photography alone should not be used to distinguish prognostic predictors, regardless of the technology applied. However, new information can improve the multimodal assessment, aiding clinical examination.

Several imaging tools and technologies can be used with different diagnostic values to assess the choroidal nevus's pathological features. We brought to light the features of these lesions when assessed by the BLFI technology, highlighting the role of RC in the better definition and characterization of choroidal nevus. We believe that this approach may provide information that might be useful both at screening, increasing the diagnostic reliability, and at follow-up, allowing a more accurate assessment of the lesion.

Ethics approval and consent to participate

The Research Ethics Committee of the Suel Abujamra Institute reviewed and approved this study protocol. This study was conducted in accordance with the tenets of the Declaration of Helsinki, and the reporting of this study conforms to the STROBE statement. The participants provided informed consent, and the confidentiality of the data collected during the survey is maintained by the authors.

Consent for publication

Not applicable.

Availability of Data and Material (ADM)

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

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

Funding

No funding or sponsorship was received for this study or publication of this article.

Authors' contributions

All authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by GCSB, EFM, EAN, and RLLG. The first draft of the manuscript was written by GCSB and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Acknowledgment

We sincerely thank the participants of this study.

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No competing interests reported.

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“Choroidal nevus through a broader vision: Retinal imaging acquisition captured with Broad Line Fundus Imaging technology.”

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