This study intends to elucidate the pathologic findings of RAP by OCT in terms and patterns which have not been depicted by previous studies. Furthermore, we attempt to propose characteristic findings of OCT in patients with RAP that may be diagnostically significant.
Materials and Methods
We studied 29 eyes of 25 patients with exudative ARMD complicated by RAP of variable onset that were identified from January, 2007 to January, 2011. The diagnosis of RAP was based on angiographic evidence (FA and ICGA) of an intraretinal neovascular complex connected with the retinal circulation, the patients were subjected to one of the three vasogenic stages described by Yannuzzi et al. [
4] (stage I: intraretinal neovascularization, stage II: subretinal neovascularization with or without PED, and stage III: CNV with RCA). All patients were older than 53 years and exhibited unique presentations of ARMD, such as soft or exudative drusen, retinal pigment epithelium (RPE) pigmentation and geographic atrophy.
None of the patients had other neovascular maculopathy that may be complicated by chorio-retinal anastomosis, such as infectious or inflammatory chorioretinal disease, angioid streaks, hereditary retinal disorders or trauma. We performed a complete ophthalmologic examination including FA (Digital retinal camera CX-1; Canon, Tokyo, Japan), dynamic ICGA (HRA2-KT-02972; Heidelberg Engineering, Heidelberg, Germany) and OCT (Spectral OCT SLO; A Division of OPKO Health, Toronto, Canada) in all 29 eyes.
Discussion
RAP has emerged as an increasingly acknowledged variant of neovascular ARMD [
4,
14-
16]. Lesions of RAP originate from intraretinal neovascularization. Branches of new vessels extend into the subretinal space resulting in RPE detachments and anastomosis with choroidal neovascular complexes [
17].
FA often results in angiographic presentations of occult or minimally classic CNV in patients with RAP. When large PED are presence, it had been difficult to reveal in RAP lesion by FA. CNV is known to originate from the choroid, then PED is formed and the fluid leaks into the retina [
3]. However, RAP originates where leakage in the retina occurs, and PED is subsequently formed. This may be why it is difficult to detect the exact location where RAP lies with FA, especially in the earliest stages of the disease with PED in RAP lesions, due to the presence of intraretinal fluid [
3,
12,
14].
ICGA is a useful tool in determining the nature of neovascularization, which appears as indistinct hyperfluorescence in FA, because it establishes the relationship between RAP and retinal circulation [
3,
10-
12]. However, both FA and ICGA are tools that give us information by two dimension image. Rouvas et al. [
3] employed Stratus OCT evaluation and revealed CNV with a small surface area beneath circular and irregular RAP lesions in focal or multifocal RAP, which provided better perspectives for understanding this disease. Thus, we believe that, investigating the non-CNV lesions that commonly accompany RAP lesions with spectral domain OCT may be helpful in the diagnosis and consideration of subsequent treatment. We investigated lesions that may occur alone or in combination in patients with RAP, and did so independently from the classification and staging proposed by Yannuzzi et al. [
4] since the true nature of RAP lesions had not been clearly identified.
Drusen, hyperfluorescent, ill-defined confluent lesions on FA which are tiny yellow or white accumulations of extracellular material that build up in Bruch's membrane. The presence of a few small drusen is normal with advancing age (>40 years old), especially in patients with progressing ARMD [
18-
20]. Drusen are typically found easily in patients with RAP; this may not be a diagnostic finding; but it may be helpful in locating other lesions and which layers of they lie within, since drusen usually appear in combination with others findings including SRD and PED.
The biomicroscopic location of RAP lesion is difficult to assess because it is usually masked by intraretinal proliferations including edema and hemorrhages [
2]. In the present study, intraretinal serous edema was commonly found in the presentation of inner retinal cyst together with FVPED. Inner retinal cysts are lesions typically accompanied by cavitation and the subsequent retinal swelling caused by accumulation of intraretinal fluid, and their layer of origin can be difficult to detect FA and/or ICGA [
6,
7-
9].
Although OCT is an excellent tool for diagnosis of the retinal alterations surrounding RAP lesions, it is limited in its ability to distinguish true inner retinal cysts from pseudocystic cavities. In the present study, whether inner retinal cysts found in RAP lesions were true cysts or pseudocystic, they were the second most commonly found lesion, after drusen (
Table 2). Moreover, regardless of their size, CNV appeared to develop subsequently and adjacent to inner retinal cysts, as a manifestation of the progression to RAP.
Along with the neovascularization of new vessels growing from the intraretinal complex of RAP, scar tissue called fibrovascular proliferation as well as FVPED may form on the surface of the retina. The fibrovascular tissue may distort the overlying RPE and outer retinal barrier leading to the spread of new vessels into subretinal space or into the neurosensory retina, causing serous detachment of the retina [
21,
22]. On FA, FVPED appears stippled hyperfluorescence within irregularly elevated PED, which shows leakage of an undetermined source, also in a stippled pattern [
11,
22]. All of the cases with FVPED found in our study were complicated by SRD and/or PED.
ORCs are a new type of cystic structure recently identified in patients with AMD, and can be differentiated from intraretinal exudates and cystoid cavities lying in the outer plexiform layer by their surrounding hyperreflective rings [
15]. Zweifel et al. [
23] reported that tubulations in the outer retinal layer result from sublethal injury to the photoreceptors and disruption of the RPE layer. When outer retinal cystoid changes are observed in patients with RAP, vision- threatening conditions should be considered in differential diagnosis to determine the most appropriate course of treatment.
Serous detachments of the RPE appear as optically clear areas between the RPE and the choriocapillaris, and a detachment can be single or, multiple, dome-shaped, or bilobed [
24]. When RAP reaches the subretinal space and merges with the RPE, a serous detachment of the RPE will develop [
2,
25]. SRD demonstrates leakage of fluorescein in the corresponding area on FA and subsequent subretinal concretions may be indicative of spontaneously resolved previous serous detachments [
3,
4]. The progression of RAP on OCT is characterized by the presence of intraretinal (well-defined confluent hyporeflective) spaces or subretinal fluid (a well-defined, hyporeflective space between the neurosensory foveal retina and other highly reflective bands corresponding to the RPE) [
2].
PED appears to be a dome-shaped, optically empty space lined by a highly reflective layer of RPE. Serous PED can often be found in the macular area where CNV lies at the margin or within the PED, and on ICGA, it can be revealed as a variable, minimal blockage of normal choroidal vessels usually evident in the midphase [
14]. Sato et al. [
26] suggested that the low height of small PED may indicate that the detached RPE and Bruch's membrane are connected by CNV.
In a comparison of BCVA, patients with FVPED and PED showed relatively lower visual acuity than patients with inner retinal cyst, outer retinal cystoid change and SRD at initial visit. Moreover, those groups with lower initial BCVA did not show improved BCVA at final visit and still showed lower levels of visual acuity regardless of the conventional treatment of RAP (
Table 2). However, analyzing the BCVA of patients in this study may not be meaningful, since the six OCT findings appeared in combinations of at least two findings, with drusen present in all cases. BCVA may not be a reliable parameter in predicting the prognosis of OCT findings. However, it may be used as a reference point to evaluate whether more aggressive treatment should be pursued based on the type of OCT finding. Thus, the course of treatment for RAP patients who have FVPED and PED as demonstrated by OCT should be carefully considered, as they tend to show lower BCVA than patients with other findings.
In conclusion, we analyzed OCT findings of RAP patients and revealed six different types of lesions distinct to RAP. These findings may be a useful tool in diagnosis, elucidating the clinical course of the disease, choosing an appropriate course of treatment and predicting prognosis. In such lesions, OCT provides more accurate information than FA or high speed ICGA, and it can be preferable to other diagnostic tools in understanding RAP. Moreover, both inner retinal cysts and FVPED commonly occur in patients with RAP, yet only inner retinal cysts as an early finding, may be a predictive of development to RAP, since FVPED is more likely to appear in more advanced stages. Limitations of this study include its retrospective nature, the relatively small sample size, short follow-up period and lack of anatomic landmarks in scanning and analyzing OCT. Further large, prospective studies based on SD-OCT technology with long follow-up periods may be necessary to discover more features of RAP that can support our findings of this study.