Retina

Evaluation of Congenital Optic Disc Pits and Optic Disc Colobomas by Swept-Source Optical Coherence Tomography Kyoko Ohno-Matsui,1 Akito Hirakata,2 Makoto Inoue,2 Masahiro Akiba,3 and Tatsuro Ishibashi4 1Department

of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan Department of Ophthalmology, Kyorin University, Tokyo, Japan 3 Topcon Corporation, Tokyo, Japan 4 Department of Ophthalmology, Kyushu University, Fukuoka, Japan 2

Correspondence: Kyoko Ohno-Matsui, Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University; 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; [email protected].

PURPOSE. To investigate the structural abnormalities of optic disc pits and colobomas by sweptsource optical coherence tomography (OCT).

Submitted: July 24, 2013 Accepted: October 17, 2013

RESULTS. Optical coherence tomography images showed the entire course of the pits from their openings to the bottom in 12 eyes. Shape of optic disc pits varied from sharp triangular cavities to longitudinally oval according to the depth of the pits. In the other four eyes, the pit narrowed into a tunnel along the optic nerve. The entire area of the optic disc was observed in three of seven eyes with disc coloboma by OCT. In all of the eyes with optic disc pits, the lamina cribrosa was torn off of the peripapillary sclera at the site of the pits. In two cases with optic disc pits and one case with optic disc coloboma, Optical coherence tomography showed SAS immediately posterior to the highly reflective tissue lining the bottom of the excavation. The distance between the intraocular cavity and SAS in these three cases were 88, 126, and 133 lm.

Citation: Ohno-Matsui K, Hirakata A, Inoue M, Akiba M, Ishibashi T. Evaluation of congenital optic disc pits and optic disc colobomas by swept-source optical coherence tomography. Invest Ophthalmol Vis Sci. 2013;54:7769– 7778. DOI:10.1167/iovs.13-12901

METHODS. Sixteen eyes with congenital optic disc pits, and seven eyes with optic disc colobomas were studied. Papillary and peripapillary areas were examined with swept-source OCT. The entire course of the pit or cavity and the spatial relationship between pits and retrobulbar subarachnoid space (SAS) were examined.

CONCLUSIONS. Swept-source OCT is able to detect different kinds of abnormalities including shape of cavities, defect of lamina cribrosa, or distance to SAS in the excavated optic discs anomalies. Keywords: optic disc pit, disc coloboma, optical coherence tomography, subarachnoid space, congenital disc anomaly

ongenital optic disc pits and optic disc colobomas belong to the same group of excavated optic disc anomalies.1 Congenital optic disc pit is observed as a round or oval, gray, white, or yellowish depression in the optic disc.1 Congenital optic pits commonly involve the temporal optic disc, but may be situated in any sector. Histologically, optic pits consist of herniations of dysplastic retina into a collagen-lined pocket extending posteriorly, often into the subarachnoid space, through a defect in the lamina cribrosa.1–3 In optic disc coloboma, a sharply delimited, glistening white, bowl-shaped excavation occupies an enlarged optic disc. The excavation is decentered inferiorly, reflecting the position of the embryonic fissure relative to the primitive epithelial papilla.1 Different from acquired optic pits, which develop in eyes with glaucoma or pathologic myopia, defective closure of the embryonic fissure of the eye and/or an impaired differentiation of the peripapillary sclera from the primary mesenchyme has been suggested to be the cause of excavated optic disc anomalies.1 Congenital optic disc pits are seen alone or occasionally in combination with optic disc colobomas.4–7 These observations suggest that congenital optic disc pits may be pathologically related to optic disc colobomas.

Approximately two-thirds of patients with congenital optic disc pits have or have had a serous retinal detachment of the macula.8 Optical coherence tomography (OCT) has shown that there are frequent retinoschisis-like separations of the retina during the development of the serous macular detachments in eyes associated with congenital optic disc pits.9 Similar macular detachments combined with retinoschisis-like separations have been reported in eyes with optic disc colobomas.10,11 However, the pathogenesis of the macular detachments associated with optic disc pits or optic disc coloboma remains undetermined. The treatment of the macular detachments associated with optic disc pits, optic disc pit maculopathy, and optic disc colobomas remains controversial. Subretinal migration of gas12 or an intracranial migration of silicone oil has been reported,13 suggesting that there is movement of fluid between the vitreous cavity and the subarachnoid space. We have reported that posterior vitreous detachment (PVD) without gas tamponade or laser treatment for optic disc pit maculopathy seemed to be effective methods of managing the macular detachments.14 The effectiveness of these treatments suggests that vitreous traction around the optic disc pit may cause passive fluid migration into the intraretinal space through the pit. We have observed during

Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783

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Swept-Source OCT of Optic Disc Anomaly vitrectomy with triamcinolone acetonide that a posterior hyaloid strand is tightly attached to the congenital optic disc pit, and it was sucked into the pit as a PVD was created.15 These suggest that traction around the posterior hyaloid may contribute to the pathogenesis of the detachment. Thus, it should be important to investigate the deeper structures of the congenital optic disc pits to determine the pathogenesis of optic disc pit maculopathy. Because it has not been possible to observe into such excavated optic disc in vivo by the existing instruments, most of the earlier studies were histopathologic studies on human cadaver eyes. These studies showed that the optic disc pits consisted of herniations of dysplastic retina into a collagenlined pocket extending posteriorly through a defect in the lamina cribrosa.1–3 In eyes with an optic disc coloboma, a widening of the scleral canal, atrophic optic nerve, and posterior displacement of the lamina cribrosa have been found in some cases.1,16 Histopathologic investigations have the advantage that the entire course of deeply excavated lesions can be observed. However, the number of the eyes that can be studied is limited, and more importantly, it is not possible to observe the same individual at different times such as before and after surgery. Recently, OCT examinations have been mainly done to evaluate macular pathologies associated with optic disc pit maculopathy,14,17–20 and only a limited number of studies have reported the OCT findings of eyes with congenital optic disc pits.21–24 However, the resolution and penetration of conventional OCT into the deeper tissue were not sufficient, thus, detailed information on the structures deep in the pit, especially the spatial relationship between the pit and the SAS, was not determined. Similarly, in the studies that evaluated eyes with optic disc coloboma by OCT,24 only the superficial areas of the papillary region were visible for study. The recent advancement in OCT technology has enabled investigators to acquire high quality images of tissues located deeper than the retina (e.g., the choroid, sclera, and the retrobulbar optic nerve and its sheath). One method is called enhanced depth imaging (EDI)-OCT, which was reported by Spaide et al.25 Imamura and Spaide21 and Hirakata et al.14 used EDI-OCT to show intraretinal fluid communicating with the cavity inside the optic nerve at the site of the optic disc pits. The other technology is swept-source OCT, which uses a wavelength swept laser as the light source26 and, in practice, has less sensitivity roll-off with tissue depth than conventional spectral-domain OCT (SD-OCT). The current swept-source OCT instruments use a longer center wavelength, generally in the 1-lm range, which has improved their ability to penetrate more deeply into tissues than the conventional SD-OCT instruments. By using swept-source OCT, we have recently been able to study the SAS around retrobulbar optic nerve in highly myopic eyes.27 Very recently, Katome and colleagues28 examined one patient with congenital optic disc pit and showed features of deep structures of this pathology by using swept-source OCT. Thus, the purpose of this descriptive study was to examine the deeper structures of excavated optic disc anomalies by swept-source OCT. We were able to examine the entire course of the excavation, the spatial relationship between the congenital pits or colobomas and the SAS, and the structure of the lamina and peripapillary sclera.

MATERIALS

AND

METHODS

Sixteen eyes of 14 patients had congenital optic disc pit, and seven eyes of four patients had an optic disc coloboma. The diagnosis of congenital optic disc pits and optic disc coloboma

IOVS j November 2013 j Vol. 54 j No. 12 j 7770 was based on characteristic fundus observations and clinical history. Congenital optic disc was observed as a round or oval pit, which appeared darker than the surrounding disc tissue and the disc itself was larger than in the unaffected fellow eyes in unilateral cases, as reported in the literature.1 None of the 16 eyes with congenital optic disc pit had glaucomatous disc cupping. High myopia was found in one patient (Case 12 in Table 1). Optic disc coloboma was observed as a very large excavation situated inferiorly, so that normal disc tissue was confined to a small superior wedge, as reported in the literature.1 All of these individuals were patients of the Kyorin Eye Center (Tokyo, Japan). The 23 eyes of 18 patients with congenital anomalies of the optic disc were evaluated by swept-source OCT between November 9, 2011 and March 9, 2012 in the Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan. The procedures used in this research adhered to the tenets of the Declaration of Helsinki and were approved by the ethics committee of Kyorin University and Tokyo Medical and Dental University. A written informed consent was obtained from all participants after a complete explanation of the procedures to be used and possible complications. Vitreous surgery with induction of a posterior vitreous detachment (PVD) at the optic disc with or without gas tamponade without laser photocoagulation earlier on 10 eyes with optic disc pits14,29 and in two eyes with optic disc colobomas because of a worsening of the visual acuity by the macular detachment. A complete macular reattachment was achieved following vitrectomy in 10 eyes, and the other two eyes had a decrease in the degree of macular detachment soon after the vitrectomy. Two eyes in the other cases had a shallow macular detachment and were not treated. The topographic distribution of the pits was divided into six distinct zones relative to the optic disc center as explained in detail in our earlier study.30 In this study, the optic disc center was defined as a cross point of the horizontal line with maximal horizontal diameter and the vertical line with maximal vertical diameter of the optic disc. Zone 1 was a 608 sector that covered 308 above and 308 below a temporal horizontal line across the center of the optic disc. The remaining five sectors of 608 surrounded the optic disc in a counterclockwise direction for the right eye and in a clockwise direction for the left eye. These sectors are referred to as zones 2 through 6.

Swept-Source Optical Coherence Tomography All of the eyes were examined by a prototype swept-source OCT instrument manufactured by Topcon Corporation (Tokyo, Japan). This swept-source OCT system has an A-scan repetition rate of 100,000 Hz, and its light source operates in the 1-lm wavelength region. The light source is a wavelength-sweeping laser centered at 1050 nm with an approximate 100-nm tuning range, although the effective bandwidth was approximately 60 nm because of water absorption. The axial resolution was calculated to be 8 lm in the tissue, with a lateral resolution of 20 lm. The imaging depth was 2.6 mm in the tissue, and the lateral scan length was adjustable. Four scanning protocols were used: three-dimensional (3D) volumetric scans, line scans, 7-lines raster scans, and radial scans. The 3D volumetric data were acquired in 0.8 seconds, and each 3D scan covered an area of either 3 3 3 or 6 3 6 mm2 with 256 (horizontal) 3 256 (vertical) A-scan densities. The scans were centered on the optic disc. To improve the image quality, three consecutive B-scan images were averaged by the weighted moving average technique. From the volumetric images, en face (C-scan plane) cross-sections were constructed by a custom-made software. The radial scan consisted of 12

OCT Findings

11 48 17 59 21 37 50

38

7 8 9 10 11 12 13

14

M

M M F F M F F

M F F M F F

L R L L L R L L L L L L R R L R

0.50 0.50 1.00 1.25 1.00 1.75 0.50 2.25 1.25 1.25 2.00 3.00 10.00 0.75 1.25 0.75

2 1 1 1–3 2 Center Center 1 1 1 1 5 1, 2 1 1 1

1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1

   þ þ           

     þ þ þ þ þ þ þ þ þ  þ

þ þ           þ†  þ þ† N/A N/A N/A 51 N/A 43 40 9 43 9 43 21 36 47 N/A 38

þ þ þ þ þ þ þ þ þ Too deep þ þ Too deep Too deep  þ

þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ

    þ      þ þ     Single Single Single Single Single Single Single Single Single Single Single Single Double Single Single Single

N, number; y/o, years-old; M, male; F, female; R, right; L, left; D, diopter; N/A, not applicable; OCT, optical coherence tomography. * See Methods for details. † Improving macular detachment after vitrectomy.

24 11 47 55 70 55

1 2 3 4 5 6

þ þ þ Not clear þ Not clear Not clear þ þ Not clear þ þ þ þ þ þ

þ þ þ Not clear þ Not clear Not clear þ þ Not clear þ þ þ þ þ þ

195 228 1071 388 1189 790 740 802 1020 678 780 582 810 1399 212 198 649 669 >1400 Not clear 1507 1101 754 607 >1094 72, 70 >1172 250 Not clear 200 685 344

 þ       þ       

Depth of the Deepest Previous SAS Retinal Lamina Point in Location Vitrectomy Visualization Tissue Displacement the Pit Diameter Visible of for Present Age at Herniation Septum From of Pit Near of the Discontinuity Toward the Case Age, Refractive Pit Number Choroidal Macular Macular Vitrectomy, Bottom Into Traversing Space of Lamina Other Opening, Opening, the Pit No. y/o Sex Eye Error, D (Zone)* of Pit Coloboma Detachment Detachment y/o of Pit Pit Space the Pit Within Pit at the Pit Side of Pit mm mm Bottom

TABLE 1. Clinical Characteristics of Patients With Congenital Optic Disc Pits

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FIGURE 1. Fundus photographs and OCT findings in an eye with shallow optic disc pits. (A) Fundus photograph of the left eye of a 24-year-old man (Case 1 in Table 1) before vitrectomy showing a temporal optic disc pit. (B) Magnified image of the optic disc showing a temporal optic disc pit (arrow). The scanned OCT lines in (C–E) are shown as green lines in (A). (C) Long, horizontal OCT scan across the pit showing a shallow pit appearing as a triangular cavity (arrow) at the temporal margin of the optic nerve head. Macular retinoschisis can also be seen. (D) Short, horizontal OCT scan across the pit showing a sharp slit corresponding to the pit. The lamina cribrosa (red arrowheads) is torn at the site of the pit and is shifted toward the opposite side of the pit. Vitreous fibers are seen to continue into the pit along the pit wall (white arrowheads). (E) Short, oblique OCT scan across the pit showing a sharp slit corresponding to the pit. Vitreous fibers are seen to continue into the pit along the pit wall (white arrowheads). (F) Fundus photograph of the right eye of a 50-year-old woman (Case 13 in Table 1) after vitrectomy showing an inferotemporal optic disc pit. The macula is mottled and appears atrophic. The scanned OCT lines in (H) and (I) are shown as green lines. (G) Magnified view of (F) showing a pit along the inferotemporal margin of the optic disc (arrow). (H) Vertical OCT scan across the pit showing a shallow pit as (white arrow) a triangular slit posterior to the inner surface of the lamina cribrosa. The optic nerve fibers are shifted toward the opposite side of the pit, and the margin of the shifted optic nerve is indicated by arrowheads. The retina is herniated into the pit along the outer border of the optic nerve. An empty cavity (red arrow) is observed deep within the herniated retinal tissue. (I) Oblique OCT scan across the pit showing that the lamina cribrosa (arrowheads) is torn from the peripapillary sclera at the site of the pit. The lamina and retrolaminar optic nerve fibers are shifted toward the opposite side of the pit. An empty cavity (arrow) is observed deep within the herniated retinal tissue. Scale bars: 1 mm.

FIGURE 2. Fundus photograph and swept-source OCT images showing long course of the pit cavity along the outer border of the retrolaminar optic nerve. (A) Fundus photographs of the right eye of a 37-year-old woman (Case 12 in Table 1) showing a temporal optic disc pit (arrow). (B) Magnified image of the optic disc showing a temporal optic disc pit. The scanned OCT lines in (D–I) are shown as green lines in (A). (C) C-scan image reconstructed from 3D OCT images showing two pits (arrows) at the temporal margin of the optic disc. (D) Oblique OCT scan across the pit showing that the entrance of the pit is narrow (arrow); however, the pit posterior to the lamina cribrosa (arrowheads) is wider. There are three holes or cystic changes near the pit entrance in the herniated retinal tissue. (E) Vertical OCT scan across the pit showing that the shape of the pit is pear-shaped with a thin septum between the two cavities. (F) Oblique scan across the pit showing an empty space (arrow) posterior to the laminar cribosa plane (arrowheads). (G) Another oblique OCT scan showing that the lamina cribrosa (arrowheads) is separated from the peripapillary sclera at the site of the pit. The lamina cribrosa and retrolaminar optic nerve are shifted toward the opposite side of the pit. The retinal herniation extends deep along the margin of retrobulbar optic nerve and an empty space is observed within the herniated retinal tissue (arrow) deeper than the lamina cribrosa. (H) Horizontal OCT scan across the pit showing that the lamina cribrosa (arrowheads) is separated from peripapillary sclera. The lamina cribrosa and retrolaminar optic nerve is shifted toward the opposite side of the pit. Two empty cavities (arrows) are observed along the temporal border of the retrobulbar optic nerve. (I) Adjacent horizontal OCT scan showing an empty space (arrow) within the herniated retinal tissue which appears to connect the two empty cavities in (H). (J) Schematic illustration of (H). The lamina cribrosa and retrolaminar optic nerve are shifted toward the opposite side of the pit. An empty cavity can be seen to continue deep into the pit along the temporal border of the retrobulbar optic nerve. The inner surface of lamina cribrosa is shown as a dotted line. ON, optic nerve. Scale bars: 1 mm.

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FIGURE 3. Fundus photographs and OCT images of deep optic disc pits. (A) Fundus photograph of the right eye of an 11-year-old girl (Case 2 in Table 1) showing a superotemporal optic disc pit. (B) C-scan image reconstructed from 3D OCT images showing one large pit. (C) 3D view of the 3D OCT image. The pit bottom is shown by an arrow. The scanned OCT lines in (D, F, G) are shown as green lines in (A). (D) Horizontal OCT scan across the pit showing a deep pit with a wide opening. The depth of the pit from its opening to the bottom is 1071 mm. Thin herniated retinal tissue can be seen at the pit bottom. A hypo-reflective space of fluid (arrow) with hyper-reflective dots can be seen just posterior to the pit bottom. This hyporeflective space is most likely the retrobulbar subarachnoid space (SAS). Vitreous fiber within the pit cavity can also be seen (arrowhead). (E) Schematic illustration of (D). Thin, herniated retinal tissue (orange) is observed along the wall and on the bottom of the pit. SAS (light blue) is observed just posterior to the pit bottom. Inner surface of lamina cribrosa is shown as a dotted line. (F) Vertical OCT scan across the pit showing that pit diameter appears to reach its maximum at a level deeper than the lamina cribrosa. SAS (arrow) is observed just posterior to the pit bottom. Vitreous fibers within the pit cavity are also seen (arrowhead). (G) Adjacent vertical scan of (F) showing that the SAS (arrow) is just posterior to the highly-reflective collagenous tissue which consists of the bottom of the pit. Hyperfluorescent dots and lines suggestive of arachnoid trabeculae are observed within the SAS. Vitreous fibers within the pit cavity are also seen (arrowhead). (H) Fundus photograph of the left eye of a 48-year-old man (Case 8 in Table 1) showing a temporal optic disc pit. The scanned OCT line in (I) is shown as a green line. (I) Horizontal OCT scan across the pit showing a deep pit with a wide opening. The depth of the pit from its opening to the bottom is 649 mm. A hyporeflective space suggestive of the retrobulbar SAS (arrow) can be seen just posterior to the pit bottom. Scale bars: 1 mm.

meridian scans centered on the optic disc. The 7-lines raster scan and line scan were performed when necessary. Each scan had a lateral scan length of either 6 or 9 mm. A single image was made up of 1024 A-line scans acquired in 10 ms. Typically, 32 B-scan images were recorded and averaged by post processing to yield a despeckled high-quality B-scan image. The measurement time for each scan was approximately 10 ms. The depth of the pits, the diameter of the pits, and the thickness of the tissue at the bottom of the pits, were measured with the caliper function of the built-in software of the swept-source OCT.

RESULTS Congenital Optic Disc Pits The demographics of the 14 patients and 16 eyes with a congenital optic disc pit are shown in Table 1. The pits were located most frequently in zone 1 (10 eyes). Other pits were located nasal or inferior to the optic disc center or in the center of the optic disc. The number of the pits was one in 15

eyes and two in the remaining eye. The average pit diameter at its opening was 490.4 6 423.1 lm. Ten eyes (9 patients) had a history of vitrectomy to treat the macular detachment associated with the optic disc pits. Two eyes (2 patients) had a choroidal coloboma inferior to the optic disc. Swept-source OCT clearly showed the entire course of the pits from its opening to the bottom of the pit in 12 of the 16 eyes (Figs. 1–5). The average depth of the pits (i.e., the distance from the opening to the surface of the herniated retinal tissue at the pit bottom) was 909 6 449.5 lm (Table 1) in 12 of the 16 eyes. In one eye (left eye of Case 2), the image quality was not sufficiently clear to identify the bottom of the pit. In the remaining three eyes, the course of the pit continued deep along the optic nerve, and we were able to observe it for only 1094 lm in Case 12 (Fig. 2), for 1172 lm in Case 13 (Figs. 1H, 1I), and for 1400 lm in Case 9 from its opening. OCT showed that the shape of the optic disc pits varied. Shallow pits appeared as a sharp triangle that extended to or beyond the level of the lamina cribrosa (Figs. 1C–1E). The shapes of the deeper pits appeared pear-shape and the

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FIGURE 4. Fundus photograph and swept-source OCT image showing a lacy appearance of the retina herniated into the optic disc pit. (A) Fundus photograph of the left eye of a 47-year-old woman (Case 3 in Table 1) without vitrectomy showing a temporal optic disc pit. The macular retina is mottled and atrophic due to spontaneous absorption of the retinal detachment. (B) C-scan image reconstructed from 3D OCT images showing a large pit along the temporal margin of optic disc. Another small pit is observed just superior to the large pit. The scanned OCT lines in (C) and (D) are shown as green lines in (A). (C) Vertical OCT scan across the pit showing a deep pit with a wide opening. The depth of the pit from its opening to the bottom is 1189 mm. Herniated retinal tissue forms a horizontal bridge across the pit cavity (red arrow). Multiple fissures (white arrow) are observed in the herniated retinal tissue. (D) In the adjacent vertical OCT scan, a horizontal bridge is separated from the cavity wall (arrow). Scale bars: 1 mm.

diameter of which was maximum at a level deeper than the laminar cribosa (Figs. 2E, 3F). In Case 12, the opening of the pit was very small (70 lm, Fig. 2D), however, the pit became much wider (605 lm) once the pit extended beyond the lamina cribosa (Figs. 2D, 2E). In 15 of 16 eyes, the pit was observed as a single cavity, however, in the remaining eye (Case 12), the pit consisted of two cavities separated by a very thin septum (Fig. 2E). The thin septum appeared to be formed by herniated retina. One of the most common OCT features of the optic disc pits was a separation of the lamina cribrosa from the peripapillary sclera at the site of the pit (Figs. 1–4). This was observed in 12 of 16 eyes (75%). The lamina cribrosa was not clearly visible by OCT in Cases 4 and 9 and both eyes of Case 6, whose pit was located in the center of the optic disc. Due to the separation, the lamina cribrosa as well as the retrolaminar

optic nerve fiber bundles appeared to be shifted away from the pit (Figs. 2, 3). A herniation of retinal nerve tissue into the pit was observed in all of the 16 eyes. The herniated retinal tissue covered the inner surface of the bottom of the pit (Figs. 3, 4). Even in the eyes whose pit seemed shallow at first glance (Case 13), a careful observation showed that the retinal herniation was continuous and extended deeply along the temporal border of the retrolaminar optic nerve (Figs. 1H, 1I). In some cases, a hyporeflective space was observed within the herniated retinal tissue, and this hyporeflective space continued far more posteriorly (Figs. 1H, 1I, 2F–2I). These observations suggested that the depth of the pit was mainly caused by the degree of filling of herniated retinal tissue into the pit. However, the herniated retinal tissue was continuous to greater depth beyond the superficially-observed pit bottom,

FIGURE 5. Fundus photographs and swept-source OCT image showing wide septa traversing the optic disc pit. (A) Fundus photograph of the left eye of a 21-year-old man (Case 11 in Table 1) before vitrectomy showing a supranasal optic disc pit and macular retinal detachment (arrowheads). (B) Fundus photograph taken 1 year after vitrectomy showing a disappearance of the retinal detachment. (C) Magnified photograph of the optic disc showing the central-to-nasal located disc pit. The scanned OCT lines in (D–G) are shown as green lines. (D) Oblique OCT scan across the pit showing a pit with a wide opening. The retina is herniated into the pit space. Two wide, horizontal septa (arrows) are seen to traverse within the pit space. (E) Horizontal OCT scan across the pit showing a deep pit with two wide septa traversing across the pit space horizontally. (F) Oblique OCT scan between (D, E) showing that multiple horizontal slits or fissures (arrows) can be seen around the septa. (G) Horizontal section, which is adjacent to (E) showing that the highly-reflective dense tissue suggestive of peripapillary sclera is abnormally protruded (arrowheads) toward the retrobulbar optic nerve and pushes the optic nerve to the opposite side of the pit. (H) Schematic illustration showing the protrusion of peripapillary sclera toward the retrobulbar optic nerve. The inner surface of the lamina cribrosa is shown as a dotted line. Scale bars: 1 mm.

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FIGURE 6. Fundus photographs and swept-source OCT images of retrobulbar SAS posterior to an optic disc coloboma. (A) Fundus photograph of the right eye of a 36-year-old man showing a large chorioretinal coloboma, which is fused to an optic disc coloboma. (B) Fundus photograph of the left eye of the same patient showing optic disc coloboma and chorioretinal coloboma. An unusual horizontal ridge-like protrusion exists within the colobomatous area. (C) Magnified photograph of the optic disc of the left eye showing a marked excavation due to optic disc coloboma and the presence of a horizontally-oriented ridge protrusion into the excavated area. The scanned OCT lines in (D–F) are shown as green lines. (D) Oblique OCT scan across the optic disc coloboma showing a deep excavation in colobomatous area. The herniated retina is detached within the colobomatous area (white arrow) as well as near the ridge (red arrow). (E) Vertical OCT scan across the optic disc coloboma, ridge-like protrusion, and chorioretinal coloboma showing that the herniated retina in the disc coloboma has a lacy appearance (white arrowheads). A ridge-like protrusion can be seen (red arrowhead). In the colobomatous area peripheral to the ridge, orbital fat tissue (red arrow) with greyish background accompanied by multiple hyperreflective dots can be seen just behind the thin sclera making up the bottom of the coloboma. Note that the orbital fat is flipped over in this image because of a limited scan depth of the OCT. (F) Surface of herniated retinal tissue has a lacy appearance and tractional changes are also seen (white arrowheads). The scanned OCT lines in (G–I) are shown as green lines in (B). (G) Long vertical OCT scan across the optic disc coloboma, ridge, and chorioretinal coloboma showing a hyporeflective space with hyperreflective bands and dots, suggestive of the SAS (white arrow) just posterior to the bottom of optic disc coloboma. Orbital fat (red arrow) exists just behind the bottom of chorioretinal coloboma. Note that the images of SAS and orbital fat are flipped over because of a limited scan depth of the OCT. (H) Short vertical OCT scan across the optic disc coloboma showing SAS with arachnoid trabeculae can be seen just posterior to the bottom (red arrow) of coloboma. The herniated retina is slightly detached from the bottom of the coloboma. (I) Vertical scan adjacent to Figure H showing SAS (white arrow) with arachnoid trabeculae in it is observed just behind the bottom (red arrow) of coloboma. (J) Schematic illustration of (H). Scale bars: 1 mm.

which suggests the possibility of a dehiscence of the optic nerve tissue from the optic nerve sheath, probably the pia mater. This was probably due to a pit formation that extended to a much deeper level than the pit depth, which was made from the superficial observations. The herniated retinal tissue was not uniform in some cases. In Case 12, there were multiple small holes or clefts within the herniated nervous tissue (Fig. 2D). In Case 3, the herniated fibrous tissue had a lacy appearance (Fig. 4C), and a part of the tissue appeared to be torn apart (Fig. 4D). In addition, a very unusual wide and highly reflective septa, which ran horizontally inside the pit were observed in Case 11 (Figs. 5D–5F). A close observation of adjacent sections showed that these wide horizontal septa appeared to originate from the peripapillary sclera, which protruded into the optic nerve (Figs. 5D–5H). In Cases 2 and 8, we were able to see the hyporeflective space containing hyperreflective granular and dot structures suggestive of the SAS just posterior to the pit bottom (Fig. 3). In these two cases, a highly reflective structure existed between the herniated retina and SAS at the bottom of the pit. This structure appeared to be continuous with the peripapillary

sclera, and its thickness was 88 lm in Case 2, and 126 lm in Case 8. Vitreal fibers that were connected to the herniated retinal tissue were observed in three of six nonvitrectomized eyes (Fig. 3). The vitreous fibers or membranes ran deep into the pit cavity in Cases 2 and 3.

Eyes With Optic Disc Colobomas Seven eyes of four patients with optic disc coloboma were examined by swept-source OCT. There were two men and two women, and the average age of the four patients was 48.4 6 18.7 years (range, 19–69 years). The average refractive error was 1.25 6 1.4 diopters (D) (range, 4.0 to 0.25 D) in these eyes. High quality OCT images could be obtained from three of the seven eyes with optic disc coloboma. In the seven eyes with optic disc coloboma, four eyes were excluded from further analyses due to the low quality OCT images, which were caused mainly by the presence of irregular surface within the area of coloboma or because of poor fixation due to a huge coloboma occupying a large area of the posterior fundus. In the end, the OCT findings of three eyes of two patients were analyzed (Figs. 6, 7). The clinical characteristics and OCT

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Swept-Source OCT of Optic Disc Anomaly

were considered to represent SAS according to our earlier observation of the periocular SAS in highly myopic eyes.31 In the other case (Fig. 7), the scleral fibrous tissue within the colobomatous area was sparse and scleral fibers appeared to be separate from each other. A hyporeflective space suggesting a gap space between the scleral fiber tissues was observed within the sclera of colobomatous area (Fig. 7D). Also, the orientation of scleral fibers was random and irregular.

DISCUSSION Congenital Optic Disc Pits Our results showed that the common OCT-determined changes in eyes with congenital optic pits were a defect of the lamina cribrosa at the site of the pits and a herniation of nerve tissue into the pits. These findings have also been reported in human cadaver eyes with congenital optic disc pits in histopathologic studies.1–3,32 During gestation at approximately the 140- to 160-mm stage (fifth month), mesodermal cells from the adjacent sclera migrate into the canal region to form the lamina cribrosa, which occurs at 7 months of gestation.33 The principal part of the lamina cribrosa is formed by an extension of collagen bundles and elastic fibers from the inner two-thirds of the sclera across the optic nerve canal.33 This developmental sequence suggests that congenital optic disc pits form because of poor migration of mesodermal elements from the adjacent sclera and poor differentiation of the mesodermal cells into the lamina cribrosa. Secondary to the focal defect of the lamina cribrosa, the rest of the lamina and the retrolaminar optic nerve are shifted toward the opposite side of the laminar defect. Similar displacements of the retrobulbar optic nerve was reported by Theodossidadis et al.34 from their study of magnetic resonance images. Our findings showed that the shape of the congenital optic disc pits varied and depended on the depth of the pits. Also, a close observation showed that the pits were deeper with the space filled with herniated retinal tissue mainly along the temporal border of the optic nerve. Thus, it is highly likely that the ophthalmoscopically-observed bottom of the pit is only the surface of the herniated retinal tissue. This then indicates that the dissociation of the retrobulbar optic nerve from the nerve sheath, probably the pia mater, extends more deeply into the optic nerve tissue. Acquired pit formation of the optic disc has been known in glaucomatous eyes based on ophthalmoscopic observation.35,36 We have recently reported the acquired pits of the optic disc in eyes with pathologic myopia by using sweptsource OCT.37 You et al.38 reported that the acquired pits of glaucoma were observed as focal lamina defects by using EDIOCT. Combining these OCT studies in acquired pits due to glaucoma38 and due to pathologic myopia37 with the findings of the current study, the appearance of the pits seemed to be similar regardless whether they were congenital or acquired. Thus, the shallow pits appeared to be triangular clefts and the deep pits appeared to be deep, linear tract along the course of the retrobulbar optic nerve or pear-shaped. The pear-shaped

FIGURE 7. Fundus photograph and swept-source OCT image of sparse and disoriented scleral fibers in the colobomatous area. (A) Fundus photograph of the right eye of a 55-year-old man showing a large optic disc coloboma and chorioretinal coloboma inferior to the optic disc. (B) Fundus photograph of the left eye of the same patient showing a chorioretinal coloboma inferior to the optic disc. The scanned OCT lines in (C) and (D) are shown as green lines in (A). (C) Horizontal OCT scan through the optic disc coloboma showing that the scleral fibers are sparse and separate from each other in the area between the arrowheads. The course of scleral fibers is irregular. (D) Vertical OCT scan through the optic disc coloboma showing that the scleral fibers are very sparse, and hyporeflective gap spaces (arrows) are observed between the sparsely-arranged fibers. Scale bars: 1 mm.

findings of these two cases are shown in Table 2. Two of three eyes had a history of vitrectomy to treat the macular detachment associated with the optic disc colobomas. Optical coherence tomography examinations showed that the optic nerve head was deeply excavated posteriorly in both cases. In the first case (Fig. 6), a herniation of retinal tissue was observed toward the colobomatous area of the optic disc. Some parts of the herniated retina had a lacy appearance (Figs. 6E, 6F), and in one case, the herniated retina was detached from the underlying highly-reflective collagenous tissue lining the bottom of the disc excavation, probably the pia mater (Figs. 6D, 6H, 6I). The lamina cribrosa was difficult to recognize because of the uneven surface within the optic nerve area. In this patient, a peculiar horizontal ridge-like protrusion traversed within the colobomatous area (Fig. 6C). In the colobomatous area outside the ridge, grayish orbital fat tissue was observed just posterior to the sclera (Fig. 6G, red arrow). However, in the colobomatous area posterior to the ridge, wide hyperreflective beams and coarse dots were seen and assumed to be structures of the trabeculae of SAS. They were surrounded by hyporeflective zones which were considered to be the fluid (Figs. 6H, 6I). These OCT features were different from the smaller punctate reflections surrounded by a gray background, which was assumed to result from orbital fat, and TABLE 2. Clinical Characteristics of Patients With Optic Disc Coloboma

History of Case Age, Refractive Choroidal Optic Vitrectomy for Present Macular Splitting of Remnants of No. y Sex Eye Error, D Coloboma Disc Pit Macular Detachment Detachment Seripapillary Sclera Tissue Inside Pit 1 2

36 55

M M

R L R

0.25 0.75 ?

þ þ þ

  

 þ þ

  

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IOVS j November 2013 j Vol. 54 j No. 12 j 7777

Swept-Source OCT of Optic Disc Anomaly deeper pits are similar to the acquired optic disc pits in highly myopic eyes,39 which also become wider once the pit deepens beyond the lamina cribrosa.39 However, congenital optic pits most predominantly develop along the temporal margin of the optic disc, whereas acquired disc pits of high myopes predominantly develop at the upper or lower pole of the optic disc.37 Ten of the eyes studied had undergone vitrectomy and three eyes had a macular detachment without previous treatment. In an earlier study, we did note that the fundus had a clearer margin, and the optic disc pit was darker after vitrectomy.14 Comparisons of preoperative fundus photographs to those approximately 1 year after vitrectomy clearly show a deepening of the excavation of the pit after complete macular reattachment. Swept-source OCT showed posterior vitreous fibers on the herniated retinal tissue within the optic disc pit cavity. The contraction of these vitreous fibers could lift the herniated dysplastic retinal tissue, which lay inside of the pit cavity to allow an invasion of fluid into the herniated retinal tissues causing the schisis-like separation of the tissue. In Case 11, the highly reflective septa that traversed horizontally across the pit appeared to be different from the herniated retinal tissue, and there was a protrusion of the peripapillary sclera toward the optic nerve. Under normal conditions, two-thirds of the peripapillary sclera differentiate into the lamina cribrosa and the remaining one-third become the pia and dura mater at the margins of the optic nerve.40 In general, the peripapillary sclera does not protrude toward the retrobulbar optic nerve. However, when the peripapillary sclera at the optic nerve margin does not differentiate into the lamina appropriately, and the proper location of peripapillary sclera, lamina, and optic nerve sheath is disrupted. We consider that this could then lead to a protrusion of the peripapillary sclera toward the retrobulbar optic nerve. We were able to see the SAS in the swept-source OCT images just posterior to the bottom of the pit in Cases 2 and 8. With the swept-source OCT, we recently reported that the arachnoid trabeculae within the SAS were clearly observed as a pattern of reticulated lines and dots interspersed with hyporeflective zones consistent with fluid in 93% of highly myopic eyes.27 There was a thin, highly-reflective tissue between the herniated retinal tissue and SAS, and the thickness of this tissue was only 88 and 126 lm. Ferry2 reported that the pit ended blindly in the optic nerve in histopathologic sections in seven cases of congenital optic pits. The margin of the scleral canal forms the temporal wall of the pit, and the pit approached the pia mater further posteriorly. From the reflective pattern and the findings of the histologic studies,2 this thin tissue bordering the SAS was considered to be the pia mater, which formed at the bottom of the pits. Although a direct communication was not identified in our images, it could be possible that a communication of fluid between the pit and SAS existed through such a thin pia mater.

Pedler,41 the sclera appeared immature and undifferentiated; the normally organized outline of its outer surface was replaced by unoriented spindle cells arranged in a coarse reticular resembling embryonic mesenchyme. A PubMed search did not extract any articles that reported a direct communication between the intraocular space and the SAS clinically or histopathologically in eyes with an optic disc coloboma. In a clinicopathologic study of an eye with an optic disc coloboma and associated macular detachment in a rhesus monkey, Lin et al.42 noted a disruption of the intermediary tissue of Kuhnt, with diffusion of retrobulbar fluid from the orbit into the subretinal space. In the present study using swept-source OCT images, the SAS was seen just posterior to the bottom of colobomatous excavation. Only thin hyperreflective collagenous tissue was observed to exist between the subretinal space and the SAS, which was considered to be the pia mater of the SAS. There are some limitations in the present study. For example, it was still difficult to obtain an image showing the entire extent of the SAS and optic nerve sheath even by sweptsource OCT. It was also difficult to obtain OCT images in good focus especially in some eyes with optic nerve coloboma, which had an irregular surface within the colobomatous area. The lack of quality images made it difficult to study the lamina cribrosa and retrolaminar optic nerve in the eyes with optic disc coloboma. Thus, it could not be determined if the morphology of the lamina cribrosa and retrolaminar optic nerve is different between optic disc pits and optic disc coloboma. In addition, the eyes studied did not have a preoperative macular detachment, and the time course of macular reattachment after vitrectomy could not be followed. Since histopathologic analysis of optic disc pits reveals perineural herniation of poorly differential retinal tissue combined with vitreous collagen around the optic nerve into the subarachnoid space,3 the fact that the majority of eyes imaged had been previously submitted to vitrectomy could have influenced their findings of herniated retinal tissue in the pit. Thus, we were not able to show the role of vitreous traction in causing the retinoschisis-like separation or macular detachments in this study. Also, there is a limitation that we had a small number of cases with coloboma compared with the cases with optic pits. Despite these limitations, the information obtained by swept-source OCT on human eyes in vivo is essential for the investigation of the pathogenic mechanisms and in clinically managing patients with these rare anomalies. In conclusion, we have investigated the papillary and peripapillary region of eyes with congenital optic pits and optic disc coloboma by swept-source OCT. The swept-source OCT images showed various abnormalities, which occur in the deep tissues such as the sclera, lamina cribrosa, SAS, and optic nerve sheath in eyes with congenital excavated disc anomalies.

Optic Disc Colobomas

Acknowledgments

The clinical and OCT findings of colobomas were similar to those of congenital pits in some cases. In Case 1 (Table 2), the OCT findings and preoperative findings were very similar to those seen in eyes with congenital optic pits, such as the detection of the SAS and the herniation of retinal tissue. Case 1 also had a macular retinal detachment accompanying the schisis-like separation before the vitrectomy. In our study, the scleral fibers in the colobomatous area were very sparse and were separate from each other. The orientation of scleral fibers was random and irregular. In a histopathologic study of a case with optic nerve coloboma by

The authors thank Duco Hamasaki for his critical discussion and final manuscript revision. Supported in part by Research Grants 22390322 and 23659808 from the Japan Society for the Promotion of Science, Tokyo, Japan. Disclosure: K. Ohno-Matsui, None; A. Hirakata, None; M. Inoue, None; M. Akiba, Topcon (E); T. Ishibashi, None

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