Sickle cell proliferative retinopathy usually presents first in the peripheral retina and the ability to extend and enhance our visualization of the peripheral retina would allow for superior clinical decision-making. In our practice, we had a 28-year-old patient diagnosed with major sickle cell disease of the homozygous type SS (HbSS) that presented with sickle cell proliferative retinopathy detected by ultra-widefield imaging in the nasal side of the left fundus. At follow-up, neovascularization was detected in the extreme nasal periphery of the left eye by ultra-widefield imaging fluorescein angiography with right gaze. The case was graded as Goldberg stage 3, and the patient was administered photocoagulation treatment. With further advancements in the quality and modality of peripheral retinal imaging, novel proliferative lesions can be detected and appropriately managed much earlier than was previously possible. Ultra-widefield imaging allows for the visualization of the central 200 degrees of the retina but, with gaze view, peripheral retina beyond 200 degrees can be reached.

© 2023 The Author(s). Published by S. Karger AG, Basel

Sickle cell disease (SCD) is the most common monogenetic disorder worldwide [1] and manifests due to a mutation in the β-globin gene that is associated with microvascular occlusions making it a multisystem, life-threatening disorder [2]. Notwithstanding the current advances in medicine and patient care, SCD has become a chronic disease and an economic burden [3].

SCD is characterized by hemoglobin S, an abnormal variant of hemoglobin A. The homozygous variety of homozygous type SS (HbSS) is associated with a more severe display than compound heterozygous varieties such as HbSC and HbSThal, where hemoglobin S coexists with other hemoglobin variants such as hemoglobin C and thalassemia hemoglobin, respectively [4].

The eye can be affected by microvascular occlusions because of SCD in several ways, such as orbital bone infarction and secondary glaucoma. However, the main sight-threatening complication is proliferative sickle cell retinopathy (SCR) which can result in vitreous hemorrhages, tractional retinal detachment, or neovascular glaucoma [5]. The Goldberg classification system is used to grade the disease and guide appropriate management. Grade I indicates peripheral arterial occlusion, grade II indicates peripheral arteriovenous anastomosis (hairpin appearance), grade III indicates neovascularization and sea fan appearance, grade IV indicates vitreous hemorrhage, while grade V indicates tractional retinal detachment [6]. Hemoglobin SC is more heavily affected by proliferative retinopathy with respect to HbSS and HbSthal. A possible explanation for this phenomenon could be related to the high hematocrit value of HbSC, causing a higher tendency of stagnated blood in small vessels leading to thrombus formation, occlusion, and ischemia. Sea fan neovascularization can appear at the edge of the ischemic area as a result of the release of angiogenic factors [5].

Laser photocoagulation is the first-line treatment used to manage SCR with an acceptable safety profile in the peripheral retina but with varying results [7]. Treatment of SCR is required at grade III of Goldberg classification. Newly diagnosed patients are followed up with different imaging modalities like fluorescein angiography and optical coherence tomography to grade the disease and determine a management plan.

Ultra-widefield (UWF) imaging has proven an important tool in grading patients with SCR – its ability to detect 200 degrees of the retina allows the far periphery to be evaluated more effectively. UWF also allows for fundus photography and fluorescein angiography (UWF-FA), although the latter proved to have better grading accuracy [8].

More importantly, UWF-FA can capture vascular borders in 98.6% of cases [8], surpassing the usual 7-standard field fluorescein angiography that could capture vascular borders in only 50% of cases [9]. With a more accurate detection and diagnosis of SCR, earlier treatment with laser photocoagulation is possible, ultimately allowing earlier treatment and delaying the complications of SCR. UWF needs fewer technical skills to image and to analyze the peripheral retina, and less time is asked to the patient, which makes it particularly useful in pediatric patients with SCR, which was recently found to be more common in the pediatric population than previously reported [10, 11]. However, Han et al. [8] found that UWF-detected changes have not changed the clinical decision. This paper explores the case of a patient with SCR, which was only detected by UWF-FA, with gaze view. This manuscript adheres to the CARE Checklist, which has been submitted as online supplementary material (for all online suppl. material, see www.karger.com/doi/10.1159/000529479).

A 28-year-old patient was diagnosed at the age of three with major SCD of the HbSS associated with a minor thalassemia trait (HbA2 of 4%). His baseline hemoglobin was determined to be 9 mg/dL. This patient had a history of multiple transfusions and suffered two single artery occlusion episodes in 2015 and 2016. He had no other comorbidities and he did not smoke. In March 2021, he was referred for screening for SCR. He underwent UWF fundus photography and UWF-FA using Optos Optomap 200Tx (California; Optos plc) (Fig. 1, 2). A small area of fluorescein diffusion was noted in the nasal peripherally of the left fundus, but fortunately no neovascularization was detected. The clinical management was to follow up in 6 months. When the patient returned for follow-up in September of 2021, further UWF imaging was taken, focusing on the nasal peripheral retina of the left eye by directing the patient to gaze to the right. Neovascularization was found in the extreme nasal periphery of the left eye, detected only by UWF-FA with right gaze (Fig. 3). The case was graded as Goldberg stage 3, and the clinical decision was to commence laser photocoagulation treatment.

Basic UWF fundus photography.

Basic UWF fluorescein angiography of the left eye, showing a small area of diffusion of fluorescein in the nasal side in the extreme periphery.

Follow-up UWF fluorescein angiography with gaze to the right, showing an area of non-perfusion, sea fan sign, with leakage of fluorescein.

SCR is less common in the HbSS homozygous type of SCD [12]. However, in this case, SCR of the HbSS type was detected using UWF retinal imaging. The presence of proliferation in the far peripheral retina, graded as a Goldberg III classification, resulted in a change of clinical management and laser photocoagulation was commenced. A conservative decision to follow up was taken as a direct result of not detecting a sea fan at the first examination even by UWF imaging. However, UWF imaging allowed us to suspect a leakage and repeat the FA a few months later in lateral gaze. By taking a more proactive approach, earlier treatment of SCR may lead to early disease control with minimal laser photocoagulation and consequently improve patient outcomes by limiting peripheral field loss [13, 14].

UWF imaging allows 200 degrees of the retina to be visualized, compared to the 75° detected by the traditional ETDRS 7-standard field visualization of the retina. This is significantly useful for the early detection of diseases that present in the extreme far periphery, like SCR [15]. ETDRS 7-standard field angiography was developed as a gold standard for grading diabetic retinopathy, however, there is no such gold standard for SCR. In addition to the limited field visualization of the ETDRS 7-standard field angiography system, it is dependent on pupil size, patient cooperation, and operator skills. These limitations are overcome with UWF retinal imaging [15, 16]. The ability to visualize 200 degrees of the retina facilitates the early discovery and management of neovascular SCR, which would otherwise remain undetected with routine fluorescein angiography [15]. UWF imaging has the ability to further enhance visualization of the peripheral retina by instructing patients to gaze in different directions, allowing a more refined image of the area of interest. The problem of image distortion due to representing a 3-dimensional structure on a 2-dimensional image has been recently resolved by a new software update that provides image processing calculations to account for the distortion of the eye surface in the retinal periphery and which also offers the advantage of improving contrasts in the posterior pole and parts of the periphery [17, 18].

UWF imaging has not yet the ability to see the entirety of the retina from ora serrata to ora serrata. However, it does provide the largest field of visualization available in retinal imaging. Additionally, further areas of the retinal can be visualized and treated by directing gaze view.

As life expectancy and the chronicity of disease increases, there will be an increase in ocular complications. This case is evidence of the potential detection of neovascularization in the extreme peripheral retina and consequently, early treatment with targeted laser photocoagulation. It is recommended to screen sickle cell patients with UWF retinal imaging to facilitate early disease detection. Using gaze view is also recommended to examine more peripheral retina.

Assistance in medical writing was provided by GP Communications, which was funded by Optos.

This study complies with the 1964 Declaration of Helsinki and its amendments. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. This retrospective review of patient data did not require ethical approval in accordance with local/national guidelines.

The authors have no financial or proprietary interest in any material or method mentioned in the study.

No funding was provided for this study.

Prof. Audrey Giocanti-Aurégan was responsible for the conception and design of the work, acquisition and analysis of data, initial drafting, and final revising of the paper. Dr. Franck Fajnkuchen contributed to the data acquisition, analysis, and the critical revision of the manuscript. Both Prof. Audrey Giocanti-Aurégan and Dr. Franck Fajnkuchen gave the final approval for the paper’s submission and both agree to be accountable for all aspects of the work.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.

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