In this study, the majority of active fellow-eye neovascularization that developed during the follow-up of unilateral neovascular AMD was detected on crosshair scans. However, approximately one-sixth of neovascularization cases could not be detected solely through crosshair scanning, and raster scanning was required for accurate diagnosis. Two factors, the type of neovascularization in the initially affected eye and the interval between fellow eye examinations, were significantly associated with undetected fellow-eye neovascularization on crosshair scanning.
In particular, the risk of failure to detect fellow-eye neovascularization on crosshair scan was 9.6 times higher in type 3 MNV, than in typical neovascular AMD. We believe that the primary reason for this finding is the characteristic lesion distribution in type 3 MNV. It is well known that type 3 MNV lesions typically develop with foveal sparing [19, 20]. The absence of a deep capillary plexus in the foveal region, which is postulated to be the origin of type 3 MNV, may contribute to the distinctive distribution pattern of the lesions [19].
Type 3 MNV is frequently accompanied by prominent macular edema and PED [21, 22]. However, during its early stages, the extent of the lesion is typically confined to a small area, presenting as small hyperreflective foci with mild edema in the surrounding region [16, 18]. For prompt diagnosis of type 3 MNV, OCT should be performed directly at the site of the lesion. This is particularly crucial when a lesion develops relatively distant from the fovea. Type 3 MNV is a progressive disease [22] with the potential for a relentless course, making the prevention of undertreatment a key aspect in its management [23, 24]. Given the potential for worse prognosis with disease progression, [25] early diagnosis is crucial for improving the treatment outcomes and prognosis. Considering the markedly high risk of fellow-eye neovascularization in type 3 MNV, it is imperative to perform raster scans and meticulously examine all acquired images during fellow-eye screening, even if it entails additional time and effort.
We propose implementing the aforementioned examination protocol even in patients with non-neovascular AMD accompanied by reticular pseudodrusen. Reticular pseudodrusen is frequently observed in eyes diagnosed with type 3 MNV [19, 26]. Moreover, the presence of pseudodrusen is speculated to be associated with the development of type 3 MNV [21]. Therefore, special attention should be paid during regular check-ups to the potential development of type 3 MNV in eyes with non-neovascular AMD accompanied by reticular pseudodrusen, and OCT raster scans should be routinely performed.
In recent years, significant progress has been made in the application of artificial intelligence (AI) in the field of ophthalmology, including the development of AI-based automated interpretation of OCT images for the detection of fluid in neovascular AMD [27]. Furthermore, an AI-enabled tool for treatment decisions in neovascular AMD is under investigation [28]. Based on the findings of this study, we believe that the development of sophisticated techniques for accurate analysis of raster scan images is crucial in establishing an AI model for determining treatment strategies in patients with type 3 MNV.
In this study, fellow-eye neovascularization was not detected on crosshair scans when the interval between fellow-eye examinations was shorter. It is possible that more frequent screenings may have led to the detection of neovascularization at an earlier stage, thus influencing study outcomes. In a previous study with type 3 MNV, a longer fellow-eye examination interval was associated with poor visual acuity and greater visual deterioration of the fellow eye at neovascularization [10]. To date, there is no established consensus for the optimal interval of fellow-eye examinations in cases of unilateral neovascular AMD. Both the present study and a previous study [10] underscore the importance of frequent fellow-eye examinations for the timely detection of neovascularization.
In contrast to the detection of fellow eye neovascularization, the diagnosis of neovascularization in the initially involved eye showed sufficient results with cross-hair scans alone in most patients, regardless of the type of neovascularization. Continuous fellow eye examinations during the treatment of unilateral neovascularization, regardless of the presence of symptoms, may allow for the early diagnosis of fellow eye neovascularization. In contrast, at the initial diagnosis, most patients visited the hospital with symptoms such as visual disturbances, suggesting that the disease was in a somewhat progressive state. This difference may lead to variations in the detection rates when using cross-hair scans alone.
This study focused on detecting neovascularization using OCT. However, in clinical practice, fundus examinations or photography are routinely used to identify retinal abnormalities. Because type 3 MNV are often accompanied by small retinal hemorrhages, [21, 29] a thorough examination of the fundus can help diagnose early type 3 MNV. In addition, advancements in OCT technology can reduce the time required to obtain raster scan images. For example, swept-source OCT consumes less time for image acquisition compared to the spectral domain OCT [30]. This advancement in OCT technology are expected to aid in detecting subtle abnormalities in the macular area through denser scanning lines.
This study had several limitations. First, this retrospective study was based on treatment data obtained in a clinical setting. Therefore, the follow-up protocol was not strictly controlled. Second, owing to the absence of monthly follow-up, the detection of fellow-eye neovascularization may have been delayed in some patients. Third, OCT angiography, which exhibits good sensitivity for detecting neovascularization in its early stages, was not routinely performed for fellow-eye monitoring. Fourth, since our study assessed active neovascularization, which is accompanied by exudation and hemorrhage, the results are not valid for subclinical neovascularization. Fourth, the sample size was relatively small. Lastly, all patients were Korean.
In conclusion, in unilateral neovascular AMD, 16% of active fellow-eye neovascularization was not detected on OCT crosshair scans but was identified using raster scans. The risk of undetected neovascularization on crosshair scans is markedly high when the initially affected eye is diagnosed with type 3 MNV. These findings suggest the need for routine OCT raster scans during fellow-eye examinations in cases of unilateral neovascular AMD, particularly in patients with type 3 MNV.
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