This is the first study that systematically evaluates the potential of WFFA in diagnosing and treating active anterior scleritis, where one-third of the patients presented with retinal findings. Studying the peripheral retinal area has helped to detect novel peripheral pathology in numerous diseases.

Now we have new diagnostic tools like WFFA to visualize the retinal and choroidal vasculature. The findings can reflect systemic inflammatory processes that affect these vascular structures. WFFA can identify areas of vascular leakage, perivascular sheathing, and occlusions, which are suggestive of active vasculitis, providing important diagnostic and monitoring information. Still, we should keep in mind that there is not always a clinical-angiographic correlation. Another advantage is that vascular changes are frequently found in the retina´s periphery, and standard field cameras (30–60º) often cannot capture them.

Retinal angiography is not frequently used as a routine diagnostic test for scleritis. In certain cases, it can help diagnose associated complications or rule out other conditions that may contribute to the inflammation [7, 8, 10].

Therefore, we conducted a study to determine whether WFFA allows us to find changes in patients with active anterior scleritis. It is important to note that retinal angiography is an invasive procedure that carries some risks and is used when other less invasive diagnostic tests have failed to provide a clear diagnosis or when there is a specific concern that can be addressed.

In normal eyes, WFFA can assess vascular perfusion of the retina, leakage, or abnormal vessel morphology. Vascular leakage in the far peripheral retina is reported in 19.8%, [13, 14] and it may show abnormal blood vessel permeability. Vascular leakage is a common finding in eyes with uveitis; peripheral vascular leakage prevalence may vary depending on age, type of uveitis, and severity. It ranges from 27% in many uveitis [12] to 75.7% in Behcet´s disease [13], with intermediate values reported for conditions such as intermediate uveitis (29%), [15] anterior uveitis (42%), [16] juvenile idiopathic arthritis (64.86%), [17] and tubulointerstitial nephritis and uveitis (TINU) (72.2%) [18]. Additionally, it may be more likely to occur in eyes with active inflammation (55% vs. 31%) [16]. In our study, we observed it in a smaller proportion (19.2%), probably because our patient’s primary site of inflammation was the sclera and presented mild active intraocular inflammation.

A retinal examination is required in all patients with scleritis, as RV at onset is typically asymptomatic until vision loss occurs, with no unusual fundus findings. RV is an extra-articular manifestation of rheumatic diseases and can be the first finding of systemic activity in a patient with non-specific rheumatologic presentations [4]. Rheumatologists have attempted to incorporate information on end-organ involvement, to develop a universal scoring system for diagnosing, staging, and treating these conditions [4].

RV can be present in all autoimmune diseases, mainly in RA, SLE, and AAV, and it is associated with increased mortality [1, 4]. RV involves endothelial inflammation, leading to vascular occlusion and eventual ischemia.

The frequency of RV findings associated with rheumatologic diseases has been reported to be up to 12% with conventional angiography [19] and 67.7% with ultra-wide-field angiography [20]. The difference between these last two studies and ours is that their association refers to RV as an isolated finding, and not in combination with active anterior scleritis. RV is usually related to an inflammatory breakdown of the retinal blood-brain barrier. Eyes with RV manifest focal, segmental, or diffuse vascular leakage [12]. It is important to determine whether there is endothelial dysfunction or if active inflammation is secondary to retinal blood vessel disruption, with focal leakage from the retinal vasculature, or obstruction of the vascular lumen [4]. Peripheral vascular leakage correlates with patients requiring additional immunosuppression, which may influence management decisions versus standard-of-care treatment [4].

We found retinal leakage in WFFA, along with CME and vascular occlusion, indicating complications of chronic inflammation. These complications are more frequent in AAV and may not been detected without imaging [8, 20, 21]. Few studies have analyzed retinal and choroidal vessels in patients with scleritis. It is postulated that necrotizing scleritis represents a primary vasculitis affecting the deep episcleral vessels, while non-necrotizing scleritis may involve a delayed hypersensitivity reaction [22]. In a microscopical examination of eyes with necrotizing scleritis, evidence shows endarteritis and periarteritis of the thickened choroidal vessels, especially associated with the scleral reaction [23].

Further, we found 24.3% of venous tortuosity in the WFFA. Venous tortuosity is observed in all types of scleritis and related systemic diseases. Many retinal pathologies consider tortuosity a negative risk factor, and modifications in retinal vessels give clues about disease severity and changes in disease activity [24]. For example, in diabetes, increased vessel tortuosity relates to hemodynamic alterations caused by the disease, including disturbed blood flow, tissue hypoxia, endothelial dysfunction, and increased levels of VEGF [25, 26]. Studies have reported associations between endothelial dysfunction and conditions such as antiphospholipid syndrome, human immunodeficiency virus, and RA. This endothelial phenomenon can occur at macrovascular and microvascular levels and has a prognostic value for cardiovascular events. For example, in RA, endothelial function improved in patients whose disease activity responded to treatment [25, 27, 28]. Understanding the associations between venous tortuosity with systemic diseases is essential in the treatment and prognosis of scleritis and related conditions.

Scleritis must be properly diagnosed to guarantee accurate and sufficient treatment to improve outcomes. The sclera is more vulnerable to inflammation because of vascular circulations [11]. Active scleritis in patients with autoimmune diseases can be a manifestation of systemic activity of the underlying autoimmune condition. Flares or worsening of scleritis often parallels increased activity or exacerbations of the systemic autoimmune disease [3]. Our study detected a systemic association with active anterior scleritis in 50% of the cases, consistent with previous literature findings [29]. The most commonly associated disease was AAV, a primary systemic vasculitis involving small vessels and it was the only one with peripheral vascular occlusion on WFFA in our study. Disease activity, including extension and subsequent damage from ischemia and necrosis, should be considered when establishing if organ-threatening vasculitis exists in addition to systemic disease [3, 30]. The second commonly associated disease was RA. In RA, elevated levels of inflammatory and endothelial dysfunction markers contribute to subclinical vasculitis due to systemic activity. This has also been seen in the choroid, with an increase in choroidal thickness [31]. A previous study described RV in 18% of patients lacking clinical signs of RV [32]. Also, in rheumatoid subclinical vasculitis, there can be a decrease in blood supply, along with a thinned choroid layer, which can produce ischemia in the foveal avascular zone [33].

WFFA has the potential to provide insights into the underlying systemic disease processes associated with scleritis and can help with treatment-related decision-making. The correlation between active anterior scleritis and changes in WFFA emphasizes the connection between ocular inflammation and systemic diseases. Therefore, patients with anterior scleritis must be accurately evaluated for systemic diseases. In addition, detecting changes in retinal angiography could quantify the response to treatment and the disease course over time [4, 12].

Our study has multiple strengths. We showed that posterior pole involvement occurs simultaneously in eyes with and without active anterior scleritis. This can play an important role in deciding whether to initiate or escalate treatment and can affect short-term or long-term morbidity and mortality. However, the study also has some limitations. The first is the small sample size. Second, there may be a possibility for selection bias, given that our hospital is a tertiary referral center. Third, this being as a cross-sectional study, we do not have the evolution of retinal findings or whether they improved with the established treatment. Finally, we did not have a control group with to compare the WFFA findings with.