Peripapillary Intrachoroidal Cavitation

Abstract

Peripapillary intrachoroidal cavitation (PICC) is a yellow-orange lesion, located at the outer border of the myopic conus. First described as a localized detachment of the retinal pigment epithelium, its intrachoroidal location was later revealed, justifying its current name. PICC is related to other myopic complications such as posterior staphyloma, but its pathogenesis is not clear to date. Although it has been considered a benign condition, most eyes with PICC show visual field defects, which leads to diagnostic uncertainty as these deficits resemble those seen in glaucoma. Furthermore, eyes with PICC may develop macular detachment with retinoschisis. Finally, misdiagnosis of PICC as a metastatic choroidal tumor may lead to unnecessary and anxiety-inducing investigations. Advances in optical coherence tomography (OCT) imaging have improved the visualization of ocular structures, contributing to the understanding of PICC. Recently, high optic nerve sheath traction forces during eye movements in highly myopic eyes have been suggested as promoters of PICC, renewing interest around this condition. However, a review of PICC is still lacking. Therefore, we aimed to provide a concise yet comprehensive overview of the current state of the art, focusing on OCT illustrations, pathophysiology and potential future perspectives based on the biomechanics of the optic nerve.

1. Introduction

Peripapillary intrachoroidal cavitation (PICC) is a myopic complication of which the prevalence is expected to increase, due to the increasing prevalence of myopia.

PICC is a well-circumscribed yellow-orange lobular lesion, located at the outer border of the myopic conus [1]. Advances in optical coherence tomography (OCT) have revealed that PICC is a hyporeflective intrachoroidal thickening [2] with little or no deformation of the overlying plane of Bruch’s membrane [3]. It appears as a neural-based triangular choroidal thickening in OCT sections crossing the optic nerve (ON) head [3,4]. A discontinuity in the border tissue of the choroid is often associated with PICC [3].

Visual field (VF) defects are reported in up to 73.3% of PICCs [5]. These VF deficits are similar to those observed in glaucoma [5], constituting a cause of diagnostic uncertainty. Additionally, macular detachment with or without retinoschisis can complicate the prognosis of PICC [6,7,8,9,10,11]. Knowledge of the PICC enables avoiding misdiagnosis as a metastatic choroidal tumor which can lead to unnecessary and anxiety-inducing investigations [1].

PICC is related to other myopic complications, namely posterior staphyloma and myopic tilted disc [4]. It is more common in eyes with a higher maculopathy category [12].

While the pathogenesis of PICC has been hypothesized for years, recent findings in the biomechanics of the ON have reopened the debate. Indeed, several methods have demonstrated high traction forces exerted by the ON sheaths on the peripapillary region of myopic eyes during ocular movements [13,14,15]. These biomechanical findings renew interest in the pathogenesis of myopic peripapillary changes because these pulling forces have been suggested as promoters of PICC [16]. In this context, we performed a thorough review of PICC with emphasis on pathophysiology using OCT illustrations and we discussed potential future perspectives.

2. Epidemiology

PICC is found in 5–17% of highly myopic eyes [4,17]. Variability in study populations and study designs interferes with the prevalence range of PICC [4,17,18].

Shimada et al. first identified the PICC in the fundus and then performed OCT imaging [17]. However, more recent studies have revealed that only 46.7% to 53% of PICCs diagnosed on OCT are detected on fundus photos [4,19,20]. In addition, they searched for PICCs in the area under the ON head and would have missed restricted PICCs in other peripapillary parts [17]. These two aspects may explain the low prevalence of PICC in this series [17].

Some studies set the minimum age for inclusion at 50 years [4] while others also recruited younger subjects [17,21,22]. Knowing that the prevalence of PICC takes off at approximately the age of 30 [17,19], the inclusion of subjects aged at least 50 years [4] focuses on those most likely to have a PICC, thus explaining the higher prevalence of PICC in these cases.

Choudhury et al. found that the prevalence of PICC was 2.2% in the whole myopic group and 22% in highly myopic eyes [18].

The mean age at diagnosis of PICC is approximately 50 years [1,2,3,5,17,21,22,23,24], ranging between 19 and 79 years [19,25]. Shimada et al. showed that the prevalence of PICC takes off at age 30 and is maintained over 70 years [17].

There is no gender predilection [1,17,22] and PICC can be unilateral (53% subjects in one series) or bilateral [1,3,19,22,23].

PICC is more common in highly myopic eyes. The reported range for axial length is between 25 and 32 mm [1,20] and the refractive error ranges from −6 D to −23 D [1,21]. However, PICC is also present in non-highly myopic eyes and even in non-myopic eyes [19,21,22]. Non-myopic or low myopic patients with PICC were significantly older than those with high myopia and PICC, highlighting the combined role of structural weakening and time [19].

PICCs do not induce loss of best corrected visual acuity, unless other myopic complications are associated [1,23]. However, VF defects are reported in 66% [23] to 73.3% of PICCs [5] and macular detachment can complicate a PICC [6,7,8,9,10,11].

Although there is no known association between PICC with intraocular pressure or systemic disease [4], an anecdotal case of acquired PICC secondary to intercalary membrane detachment has been reported in an eye with coloboma [26].

3. Clinical Investigations and Diagnosis of PICC

3.1. Fundoscopy and OCT

The yellow orange ophthalmoscopic appearance of PICC [1,3,4,17,19] (Figure 1A) is obvious only in 46.7% to 53% of OCT-detected PICCs [4,19,20]. Therefore, OCT is the recommended tool for the screening of PICC.

OCT reveals a spectrum of PICC appearances depending on the location and orientation of the section (Figure 1B). At the level of the peripapillary zone, it shows an aspect of hyporeflective intrachoroidal thickening [2] behind the plane of Bruch’s membrane (Figure 1C). If the section is through the ON, the PICC shows a triangular choroidal thickening (Figure 1D) with the base at the ON head. The well-demarcated border tissue of choroid (Figure 1D) may show discontinuity (Figure 1E,F).

The lesion is mainly located below the ON head [1,2,3,5,12,17,19,21,22,24]. However, other peripapillary areas may also be involved [4,10,12,17,22,24], and the PICC may even surround the entire ON head [17,19]. Therefore, Shimada subdivided it into three grades based on its overall circumference around the ON head [17].

Using spectral domain OCT or swept-source OCT, the diagnostic features of PICC are currently well established [2,3,21,22,27], obviating the need for other more invasive modalities such as fluorescein or indocyanine green angiography, the characteristics of which are summarized below.

3.2. Fluorescein Angiography

The sequence of fluorescein angiography shows early hypofluorescence followed by late hyperfluorescence without dye pooling in the area of PICC [1,2,17,22,23,28,29]. This angiographic sequence may be explained by structural choroidal changes. The early phase (hypofluorescence) results from disorganization, thinning, and loss of normal choroidal architecture while the late phase (hyperfluorescence) without dye pooling is related to the scleral impregnation by the dye, visible through the disorganized choroid [29].

3.3. Indocyanine Green Angiography

The area of PICC shows hypofluorescence throughout the indocyanine green angiography sequence [2,3,17,23]. This indicates slow or absent choroidal flow.

3.4. OCT-Angiography

Analysis of highly myopic eyes showed that the vessel density of the radial peripapillary capillary network [30,31] (Figure 2B) and that of the ON head layers [30] were significantly reduced in eyes with than in those without PICC. Highly myopic and low myopic eyes also showed a reduced vessel density compared to non-myopic eyes [30].

In a study of 47 glaucomatous eyes with PICC, Kim et al., using En-face OCT-A images at the choroidal layer, described two main vascular features. First, they noted a well demarcated homogeneous area of vessel density reduction matching the location of PICC [24] (Figure 2C). Second, they observed in 89.4% of cases, a choroidal microvasculature dropout (i.e., a focal sector with no visible choroidal and choriocapillary network). These similar patterns were previously reported in two case-reports of non-glaucomatous PICCs [32,33]. Using B scans of the OCT-A, Kim et al. showed that the PICC maintains the choriocapillary signal against the posterior surface of the Bruch’s membrane whereas it shows no signal in the intrachoroidal cavity [24] (Figure 3).

3.5. Other Modalities

Multimodal imaging [29,34,35] and three-dimensional reconstruction imaging [36] have been used in some cases of PICC, confirming the multiple facets of PICC. Azar et al. used fluorescein angiography and En-face OCT [29]; Chen et al. combined multicolor imaging, ocular B-scan ultrasonography, En-face OCT and enhanced depth imaging OCT [34]; Shen et al. used ocular ultrasonography A and B, fluorescein angiography and OCT [35].

By comparing conventional color fundus photography to multicolor imaging in a case of PICC, Venkatesh et al. found that the multicolor imaging would be less effective than conventional color fundus photography in diagnosing PICC in myopic eyes, which requires confirmation [37].

More recently, Fujimoto et al. developed a method of deep learning-based noise reduction and three-dimensional (3D) rendering of volumetric swept-source OCT images. Using this technology, they calculated the 3D volume parameter of PICC and assessed its value in detecting and understanding this condition. They found that the volume of PICC, as a new 3D parameter, reflects its influence on visual function [38].

4. Association of PICC with Other Myopia-Related Changes

Although the pathophysiological mechanisms that underpin its OCT features remain to be understood, PICC is linked to several myopic changes. It is consistently located at the outer margin of the myopic conus [1,2,3,5,17]. It is correlated with myopic tilted disc and posterior staphyloma [4,39]. All cases of Freund’s series exhibited fundus complications of severe myopia [1].

4.1. Gamma Peripapillary Atrophy

PICC is always found at the outer margin of the conus [1,2,3,5,17,21]. Recent studies have shown that this region, also called γ-peripapillary atrophy (γPPA), is acquired [40,41], and results from stresses applied locally during myopic elongation of the eye [13,15,41]. It extends from the opening of the scleral canal to the edge of Bruch’s membrane. The disappearance of Bruch’s membrane in this area is confirmed by histological studies [42] and is visible on OCT [43].

4.2. Tilted Disc

Dai et al., by intraindividual inter-eye comparison of patients having unilateral PICC, showed that the eye with PICC was more spindle like because of a pronounced tilt [20].

The tilted disc is reported in 75% to 93.5% of cases of PICC, depending on the series [1,17]. A more recent study showed a prevalence of 100% [3].

A quantitative approach to estimate the magnitude of a disc tilt would be useful in assessing the true prevalence of tilted disc in the PICC [4,20,44].

4.3. Posterior Staphyloma

Posterior staphyloma is reported in 40.2% to 100% of PICC [19,45]. This discrepancy in prevalence may result from the study design and the diagnostic tools used [21,46]. Recently, wide-field OCT has shown its sensitivity to detect inconspicuous cases while also revealing the outermost border in case of very wide types of posterior staphylomas. It is therefore recommended for diagnosing posterior staphyloma [46,47].

Since tilted disc and posterior staphyloma are more common in myopic eyes [1,4,17], it is not surprising to find a higher prevalence of PICC in this refractive eye group.

4.4. Others

Myopia-related macular changes were found in 14% to 100% of eyes with PICC [1,19]. These include myopic macular degeneration, myopic choroidal neovascularization, foveoschisis, lacquer crack, patchy atrophy, retinal holes, and macular puckering [1,17,19,22,23].

5. Structural Changes in the Vicinity of the PICC

5.1. Peripapillary Atrophy

As mentioned above, each PICC is located at the outer margin of γPPA. The area of γPPA exhibits a posterior deformation of the sclera. Recent studies have suggested that the stress exerted in the peripapillary region during adduction may promote the emergence of γPPA. This stress is more marked at the location of γPPA [48].

5.2. Choroid

Intrachoroidal hyporeflective cysts and hyporeflective hollows, disclosed by OCT, witness that in addition to choroidal thickening, PICC exhibits other structural changes inside the choroid [3,19,21,22,27]. These hyporeflective intrachoroidal cysts (Figure 4) were found in 19% to 39% of eyes with PICC [19,22]. Wei et al. described them as choroidal splitting or schisis adjacent to pocket-like spaces [22], while Yeh et al. reported intrachoroidal schisis characterized by intracavitary cleavage bands and fluid-like images [19].

Additionally, areas adjacent to intrachoroidal cysts show abnormal patterns of choroidal vessel [3]. Changes in the choroidal vascular signal were discussed in the OCT-A section above.

Considering the intrachoroidal hyperreflective line located in front of the hyporeflective space and separating this space from what appeared to be the residual initial choroid, Spaide et al. suggested that PICC was a suprachoroidal detachment [3]. This hypothesis is supported by a more recent study in which a suprachoroidal detachment was identified exclusively in cases of PICC [16].

Finally, Ehongo et al. studied the configuration of the posterior curvature of the choroid from the peripapillary polar regions to the opening of Bruch’s membrane using OCT. They highlighted a peculiar sequence of choroidal deformities associated with PICC, suggesting the role of mechanical forces in its pathogenesis. In particular, they described the presence of a posterior wedge deformity of the choroidal wall on the γPPA side, implying the existence of cross-forces at the level of the polar peripapillary regions [16].

5.3. Posterior Scleral Curvature

The sclera is deformed backwards in the PICC [3,17,21]. Spaide et al. have suggested that the choroidal thickening presented by PICC results from a posterior excursion of the sclera while the profile of the retinal pigment epithelium remains preserved [3].

A defect in the deep scleral layer allowing the exit of the inferior temporal vein into the extrascleral space associated with an unusual anatomy of the parapapillary region has been reported in a case of PICC [49].

5.4. Border Tissue of the Choroid

The border tissue is a fibro-astrocytic differentiation separating the nerve fibers from the surrounding structures (the choroid and the sclera) in the neural canal. It extends from the sclera at the level of lamina cribrosa to the Bruch’s membrane [50,51,52]. It is divided into two parts: the border tissue of choroid (Jacoby) lining the choroid, and the scleral border tissue (Elschnig) at the level of the sclera [50]. As the myopic conus extends during the myopic lengthening of the eye, the border tissue of choroid stretches [42]. A discontinuity in this structure has been disclosed using OCT [1,3,17,19,21,22,23] (Figure 1E,F).

This discontinuity was first described as a cleft in the junction between the conus and the edge of the PICC in several studies since Freund’s paper [1,3,17,19,21,22,23] (Figure 4C). Its prevalence varies from 10% to 46.2% [1,22]. Through this full-thickness defect that enables communication between the PICC and vitreous cavity, nerve fibers (Figure 3B,C and Figure 4C) and retinal vessels (Figure 4E) have been shown to herniate into the PICC [1,3,17,25].

Discontinuity of the border tissue of the choroid would be caused by mechanical stresses exceeding its resistance and leading to its rupture. Several mechanisms have been mentioned; Toranzo et al. discussed the stress resulting from the posterior progression of peripapillary staphyloma [2]. Spaide et al. mentioned the stress related to the posterior deformation of the sclera within the thinned and fragile structures of the myopic conus [3]. Dai et al. suggested mechanical forces caused by papillary tilting [20]. Ehongo et al. discussed mechanical stress induced by the traction of the ON meninges during adduction [16].

Recent versions of OCT allow to refine the diagnosis of this discontinuity by detecting it at the stage of a simple interruption of the hyperreflective line which characterizes choroidal border tissue in up to 25% of PICCs [3] (Figure 5).

5.5. Vessels

There is often a marked bending of the inferotemporal retinal vein (Figure 4E) into the steep excavation exhibited by the PICC at its junction with the conus [3,17,19,23]. This vessel sometimes disappears on part of its course in some PICCs with deep and steep excavations [3,17,19].

OCT-A features of PICC have been discussed above (Clinical investigation); Reduced vessel density in the En-face OCT-A at the choroidal level [24,32,33] is reported. Reduced vessel density in the radial peripapillary capillary plexus is also described [30] as well as that of the ON head layer [30]. Finally, the intrachoroidal cavity shows no vessel signal in the B scans of OCT-A [24] (Figure 3).

An increase in visibility of peripapillary intrascleral vessels probably related to their dilation and scleral thinning has recently been demonstrated in the vicinity of PICC [53]. Further studies are warranted to clarify this finding.

6. Clinical Relevance of the PICC

Although the PICC has been considered a benign entity, it deserves special attention. A recent series showed that it was more common in the eyes of higher categories of myopic maculopathy [12]. Additionally, VF defects [5,23,24] and macular lesions (retinoschisis, macular detachment) can complicate the presence of a PICC [6,7,8,9,10,11].

6.1. Visual Field Defects and PICC

The main clinical significance of PICC is VF defects, which are reported [5,17,19,21,22,23,24,38,54] with a prevalence ranging from 37.5% to 73.3% [5,22]. They mimic glaucomatous VF defects, hence the concern about them [5,17].

A correlation has been found between the distribution of VF defects and the location of the PICC in some cases [5,23,38]. Analyzing glaucomatous eyes with PICC, Kim et al. Found that 98% of eyes had hemifield VF defects at the location corresponding to the hemispheric location of PICC [24].

The exact mechanism underlying VF defects in PICC is not established. It has been suggested that full-thickness defects, thinning, or disruption of nerve fibers at the PICC–conus junction may explain some of these VF defects [23].

Recently, Okuma et al. showed a correlation between the location of PICC and that of the reduced thickness of macular ganglion cell complex in 66.7% of cases, using OCT [5]. They also showed a correlation between the distribution of VF defects and PICC locations in 53.3% of cases, concluding that VF defects in PICC are similar to those in early glaucoma [5].

As a correlation between the location of the PICC and the distribution of VF defects is not found in all cases, this suggests that some of the VF defects found in eyes with PICC might result from myopic distortions. In Support of this hypothesis, Shimada et al. found VF defects in 23% of myopic eyes without PICC in their series [17].

Finally, a disc hemorrhage was found in a PICC without VF defect or reduction in the peripapillary nerve fiber layer [55]. In another case, VF defect could not be detected, even when testing the full-thickness defect exhibited by the PICC using microperimetry [25].

6.2. Macular Abnormalities and PICC

From the first descriptions of PICC, a direct communication between the PICC and vitreous cavity at the junction between the conus and PICC has been reported [1,3,17] (Figure 6). Then, it was revealed that macular retinoschisis and macular detachment can complicate the presence of a PICC [6,7,8,9,10,11,12,56].

The pathophysiological mechanisms underlying macular detachment complicating a PICC involve two communications with the PICC cavity [6,7,8,10]. First, a connection to the vitreous through the full-thickness defect at the junction between the PICC and the conus, allowing vitreous fluid to access to the PICC cavity. Then, a second connection between the subretinal or intraretinal space and the PICC cavity (Figure 6). A narrow path connecting the PICC to the schisis has been documented in some cases [6,7,8]. It is suggested that this channel results from a rupture in the atrophic and dysplastic herniated retinal tissue, allowing vitreous fluid to track subretinally [6,7]. Vitreous traction [11] or peripapillary epiretinal membrane [8] have been implicated in some cases.

Although one case of self-resolving recurrent macular detachment and retinoschisis in one eye with PICC [56] has been reported, many cases of macular detachment with or without retinoschisis have undergone successful vitrectomy [8,10,11].

7. Differential Diagnosis—Natural History of Uncomplicated Cases of PICC

7.1. PICC and Differential Diagnosis

Nowadays, the diagnosis of PICC using the new versions of OCT (spectral domain-OCT and swept-source OCT) is well defined [3], thus making it possible to avoid unnecessary and more invasive and anxiety-inducing investigations.

Additionally, for physicians unaware of the condition, the sequence of fluorescein angiography mentioned above helps differentiate PICC from other potentially confounding entities, namely pigment epithelial detachment, peripapillary choroidal neovascularization, metastatic lesion or central serous chorioretinopathy [2,17].

Finally, OCT-A is a non-invasive complementary diagnostic tool to PICC [24,32,33,34].

7.2. PICC and Glaucoma

PICC is asymptomatic [1,17] and has a good prognosis. However, as mentioned above, other vision-threatening myopic complications may accompany PICC [1,22], and VF defects are reported in PICC [5,17,19,21,22,23,24,38,54].

While the prevalence of PICC regarding the refraction is well known [4,17,18], the proportion of PICC in glaucomatous eyes remains to be analyzed.

Importantly, glaucoma-like VF defects were reported in 66 to 73.3% of PICCs [5,17]. Interestingly, these deficits were found to have a location corresponding to the hemispheric location of PICC in 53.3% to 98.0% of cases [5,24]. Moreover, thinning of ganglion cell complex correlating the location of PICC was found in 66.7% (10/15) of eyes with PICC [5].

Hence, when PICC and related alterations are visible on the fundus or detected by OCT, this enables considering their potential link with VF defects found in the corresponding hemispheric location [5,24,54]. However, as PICC is detected on fundus in approximately 50% of cases [4,19,20], the presence of PICC should be considered in myopic eyes with glaucoma-like VF defects and should prompt to search for PICC by OCT.

When it comes to treatment, Shimada et al. reported that of 22 eyes with VF defects, 18 were receiving glaucomatous medical treatments [17]; Wei et al. reported 6 eyes (37.5%) treated with drops for VF defects or structural alterations [22]. As VF defects in myopic eyes tend to have a slight progression under simple observation the benefit of anti-glaucoma drugs in PICC remains to be demonstrated [54].

Finally, the pathogenetic mechanisms between PICC and VF defects are still poorly understood.

7.3. Natural Course of PICC

In general, the PICC is stable. However, Freund et al. showed, in their series, a case of involution of the PICC in both eyes of the same patient over a follow-up of 15 years [1]. In these eyes, the PICC became smaller as γPPA widened towards it.

The case reported by Toranzo et al. showed enlargement over 10 years [2]. Forte et al., using En-face OCT, observed PICC enlargement in one of six eyes in their series over an 18-month period [23]. Lee et al. reported an enlargement of the PICC over one year, followed by its shrinkage over another period of one year [55].

Formally, the condition being acquired and related to myopic complications, it is not surprising that it shows changes, albeit slow, over time, as the myopia and its structural modifications progress.

Finally, the recently developed 3D volume calculation method [38] could prove promising for monitoring PICC volume over time and its influence on the VF.

8. Pathogenetic Hypotheses of PICC

So far, the pathogenesis of PICC is not established. Congenital, fluidic and mechanical hypotheses have been proposed. Similarities between PICC and the morphologic features at the border of the optic disc coloboma have been discussed [54]. All these pathogenetic hypotheses have weaknesses or shortcomings and are summarized below.

8.1. Congenital Hypothesis

Similarities between OCT characteristics of PICC and morphological features at the border of optic disc coloboma have been discussed [57].

Some authors have suggested that PICC could be an incomplete form of choroidal coloboma because it is mainly located in the inferior peripapillary region [1].

However, PICCs can extend widely around the papilla and some PICCs are restricted to the upper part of the peripapillary area which does not support this hypothesis [17]. Moreover, PICC is observed at approximately the age of 30 [17], suggesting that it is an acquired condition. Finally, its correlation with myopic tilted disc, γPPA and posterior staphyloma [4] suggests that it is another myopia-related condition.

8.2. Fluidic Considerations

Since the lesion is more common below the ON head, Freund et al. hypothesized that there might be gravitational displacement of subretinal fluid from the area of the ON [1]. This fluid would come either from the vitreous or from the optic canal [1].

Yeh et al. finding that subjects with non-myopic eyes and PICC were significantly older than those with myopic eyes and PICC, suggested that with aging, the transitional weakened tissue of the conus might present impaired resorption of fluids from the subretinal space, subarachnoid space, optic canal or vitreous cavity. The progressive and asymptomatic gravitation of these fluids would promote the formation of fluid pockets at the level of lower edge of the conus, hence the appearance of PICC [19].

However, this gravitational hypothesis does not explain why some PICCs are confined to the upper peripapillary part [4,17,22].

Many authors have suggested that the vitreous fluid enters the PICC through the retinal defect located at the PICC–conus transition zone [17,22,23]. In support of this hypothesis, Spaide et al. observed that PICCs with the opening against the vitreous showed a more prominent posterior bowing [3], while those without this opening showed a triangular thickening of the choroid with a neural base.

Wei et al. suggested that after the rupture of the border tissue, the influx of vitreous fluid into the choroid would create a schisis or fluid pocket in the choroid [22]. They suggested that schisis and PICC might be different stages of the same phenomenon [22].

8.3. Mechanical Considerations

Wei et al. suggested that a complex of forces combining “posterior expansion force, vitreous tractional force and vitreous fluid dynamics would determine the size and shape of the PICC” [22]. However, vitreous traction has never been demonstrated in any uncomplicated case of PICC [3].

Lee et al. reported a case of PICC in a non-glaucomatous myopic eye accompanied by a large adjacent disc hemorrhage. A schisis in the prelaminar ON tissue was also noticed. At the one-year follow-up visit, the schisis and PICC had widened while the disc hemorrhage was still observed. The disc hemorrhage disappeared at the 2-year follow-up visit and the PICC showed shrinkage while the intraneural cyst was reduced. These changes suggest the presence of peripapillary mechanical forces [55].

Dai et al. showed by intraindividual inter-eye comparison that the eye with PICC was more tilted and more rotated, also suggesting the role of mechanical factors [20].

8.3.1. PICC as a Complication of Peripapillary Staphyloma

Toranzo et al. suggested that the increased gap between Bruch’s membrane and the scleral planes resulting from thickening of the choroid as the posterior staphyloma progresses, stretches the border tissue which eventually ruptures. Secondarily, the choroid retracts from the ON margins, leading to a PICC [2].

Wei et al. added that adhesion of the retina and retinal pigment epithelium to the margin of the conus prevents the rupture from opening into the subretinal space [22].

8.3.2. PICC as a Complication of Myopic Tilted Disc and Myopic Conus

As already mentioned, in the presence of γPPA (myopic conus), the sclera may be bowed posteriorly, giving rise to many suggestions.

Many authors have assumed that the posterior scleral bulge of the conus was favored by its weakening due to the absence of overlying structures [3,21]. From there, the force acting to deform the sclera depends on the author.

Shimada et al. hypothesized that during the process of γPPA extension the conus and the surrounding peripapillary area bow posteriorly. Mechanically, this induces a stretching of the tissues which then causes splitting of the neighboring intrachoroidal structures, with appearance of cysts inside the choroid. Then, the intrachoroidal cysts enlarge, coalesce, and end up in a large hyporeflective intrachoroidal space [21]. However, the flaw with this hypothesis is that the phenomenon of coalescence is not instantaneous. Therefore, hyporeflective intrachoroidal cysts, as precursors of PICC should also be found in the eyes of non-PICCs, which is not described in the literature. Further studies of longitudinal design should thus focus on these intrachoroidal cysts to clarify their impact on the pathophysiology of PICC.

Spaide et al. suggested that the driving force which is intraocular pressure against the wall of the eye induces the bulging of the weakened conus [3]. These authors explained that the stress/strain relationship ends with a more scleral deformation of the conus due to the absence or thinning of the tissues covering the sclera in this area. Subsequently, the posterior bowing of the sclera would itself favor the thickening of the neighboring choroid mainly in the inferior border of the ON. Finally, the widening of the choroid at the junction of the ON ends up breaking the border tissue, the latter promoting itself and secondarily the thickening of the choroid by allowing the entry of the vitreous fluid into the PICC [3].

Since the sclera of the conus deforms backwards, Forte et al. [23] hypothesized that the overlying structures are subjected to the same tendency. Unable to follow the strong posterior excursion of the sclera, they detach from choroid, thus creating the zone of cavitation inside the choroid and choroidal thickening.

8.3.3. PICC as a Complication of the Optic Nerve Sheaths Traction

Toranzo et al. hypothesized that in posterior staphyloma, the choroidal border tissue ruptures when stretched by the increasing gap between the plane of the sclera and that of Bruch’s membrane [2]. The driving force that increases the gap between the sclera and the Bruch’s membrane is unknown.

Beside their main hypothesis (intraocular pressure effect), Spaide et al. also opened the door to the possibility that in the tilted disc, unknown forces might be at play to bow the sclera backwards [3].

The question that remained open for years was: why in PICC does the sclera deform posteriorly while the overlying anterior structures remain undeformed?

Recent studies on the biomechanics of the peripapillary region have shown by several methods that the ON sheaths exert strong tensile forces on the ON head and the peripapillary region [13,14,15] during eye movements. From the similarities between the tilted disc and intermittent distortions of the ON and peripapillary structures related to eye movements, some authors have suggested that tilted disc would result from remodeling and permanent fixation of these repetitive deformations [15,48,58,59]. Interestingly, a case of a preoperative round disc becoming oval after trabeculectomy has been reported [60]. The eye was highly myopic and had very high preoperative intraocular pressure. It seems that this elevated pressure counteracted the ovality of the disc. Therefore, the surgical reduction in eye pressure had promoted the return to the oval shape of the disc by altering the balance of forces acting on the ON head, suggesting that the phenomenon of tilted disc can be reversed to some extent. This constitutes an avenue to explore, because PICC and tilted disc are related.

In this regard, very recently, Ehongo et al. confirmed that PICC is a suprachoroidal detachment (Figure 7A). They suggested that it was caused by the traction exerted by the ON sheaths on their scleral insertions [16]. They observed using serial OCT sections that the detection of the thickening of the choroid and the posterior bowing of the sclera, coincided with the detection of the scleral insertion of the dura mater (Figure 7A–F). The slope of the posterior bowing of the sclera steepened in front of the subarachnoid space, with the choroidal thickening ending in a suprachoroidal detachment (Figure 7A). They thus suggested that the posterior excursion of the sclera would result from the direct posterior traction exerted by the ON sheaths on the thinned and weakened myopic sclera (Figure 8). Due to this traction, the scleral flange (the part of the sclera between the margin of the ON and the dura mater) would recede while Bruch’s membrane, due to its structural rigidity would maintain its plane. This would lead to thickening of the choroid [16]. Further studies are warranted to confirm this hypothesis.

Again, relying on serial OCT sections, they observed that the convexity of the posterior choroidal wall was followed at its edge by an anterior elevation, suggesting that ON sheaths traction force would have two components [16]. The first which would act directly by protruding the sclera backwards. The second tangential component which would squeeze the choroid at the edge of the scleral convexity. This choroidal sequence would characterize a peripapillary staphyloma (Figure 8). They therefore suggested that peripapillary staphyloma would result from remodeling and permanent fixation of these repetitive deformations induced by pulling of the ON sheaths on the peripapillary sclera during eye movements [16]. These same repetitive traction forces have been suggested to promote the appearance of tilted disc [15,48,58,59].

9. Conclusions and Perspectives

The current increasing prevalence of myopia opens the way to that of high myopia and its complications, in particular posterior staphyloma, the presence of which classifies an eye in the group of pathologic myopia.

Peripapillary staphyloma and tilted disc are related to PICC. They have all been suggested to be promoted by the traction of the dura on its scleral attachment during eye movement. The link between these three complications of high myopia needs further investigation. Biomechanical and longitudinal studies are thus warranted to clarify mechanisms leading to them.

Tractions of the ON sheaths on the peripapillary region are exerted on all the eyes. On elongated myopic eyes, for obvious geometric reasons, these traction forces are more marked, promoting the occurrence of peripapillary myopic complications. However, these complications also occur, although less frequently in non-highly myopic eyes. Unknowns therefore remain as to whether the eyes undergoing these changes are more sensitive to ON sheaths traction force or whether this traction force is stronger in the eyes presenting these entities.

In particular, the influence of time and age justifies additional investigations since subjects with PICC and non-high myopia were found to be older than those with PICC and high myopia.

VF defects in PICC pose diagnostic difficulties with glaucoma (the prevalence of which is also increasing). Understanding the pathogenesis underpinning the occurrence of PICC and other peripapillary myopic complications will enable the development of strategies to slow or reverse their onset and associated VF defects.

A synopsis of publications on PICC is presented in the Appendix A.