Graefes Arch Clin Exp Ophthalmol DOI 10.1007/s00417-014-2830-0
RETINAL DISORDERS
Macular retinoschisis associated with glaucomatous optic neuropathy in eyes with normal intraocular pressure Makoto Inoue & Yuji Itoh & Tosho Rii & Yoshiyuki Kita & Kazunari Hirota & Daisuke Kunita & Akito Hirakata
Received: 24 August 2014 / Revised: 25 September 2014 / Accepted: 1 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose The purpose of this study was to evaluate the clinical features, optical coherence tomography (OCT) findings, and surgical outcomes of eyes with macular retinoschisis associated with glaucomatous optic neuropathy and normal intraocular pressure (IOP). Methods In this retrospective interventional observational study, 11 eyes of 11 patients who underwent pars plana vitrectomy for macular retinoschisis and glaucomatous optic neuropathy were studied. All eyes had a vertical cup-to-disc ratio of ≥0.7 and retinal nerve fiber layer (RNFL) defects. Intraocular pressure (IOP) was 500-nm for detection. Nine single-image frames were averaged (8.8 frames/sec) using the Automatic Real Time (ART) composite function to obtain high-quality images. The pre- and postoperative IOP was measured with a Goldmann applanation tonometer. The presence of glaucomatous optic neuropathy was diagnosed by a glaucoma specialist based on stereoscopic fundus examinations. The examinations showed the presence of an increased cup-todisc ratio, neuroretinal rim narrowing, and retinal nerve fiber layer (RNFL) defects. Gonioscopy was used to evaluate the anterior chamber angle. The visual field sensitivity (standard automated perimetry) was measured with a Humphrey field analyzer (Humphrey/Carl Zeiss Meditec, Dublin, CA) using the 30–2 Swedish interactive threshold algorithm. The results of visual field sensitivity testing were confirmed after the resolution of macular retinoschisis and detachment. The presence of an acquired optic nerve head pit with a defect of the lamina cribrosa at the cupped disc was also evaluated in the OCT images. Circumpapillary RNFL thickness was detected by OCT (OCT 4000 Cirrus-HD-OCT, Carl Zeiss Meditec, Dublin, CA; Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). Eleven eyes underwent vitreous surgery. All surgeries were performed under retrobulbar anesthesia. The surgical procedures included the creation of a PVD if one was not present, as well as both peeling and no peeling of the internal limiting membrane (ILM). Two eyes underwent fovea-sparing ILM peeling to remove the ILM except around the fovea [26]. As 10 of the patients were over the age of 60 years, cataractous lenses were extracted during the vitrectomy to avoid a reduction in postoperative visual acuity due to the cataracts. Eyes
Graefes Arch Clin Exp Ophthalmol
with a cataractous lens that affected visual acuity were excluded. The presence of PVD was determined with ophthalmoscopy and spectral-domain OCT (SD-OCT). SD-OCT was also used to detect the presence of retinoschisis, foveal detachment, or outer retinal hole, including dehiscence of the external limiting membrane (ELM) line. The axial length and bestcorrected visual acuity (BCVA) were determined preoperatively as well.
Results Preoperative clinical characteristics The demographics and clinical features of the eyes of the 11 patients with macular retinoschisis associated with glaucomatous optic neuropathy are shown in Table 1. The mean age of the patients was 69.7 ± 6.4 years, with ages ranging from 60 to 81 years. The affected eye was the right eye in four patients and the left eye in seven patients. All cases of macular retinoschisis were unilateral, but the glaucomatous optic disc cup and stereoscopic RNFL defects were present in both eyes in all patients. Ten eyes were phakic, with a mean refractive error (spherical equivalent) of +0.1 ± 1.4 diopters (D) and a range from +1.5 to −2.25 D. The preoperative BCVA was 0.86 ± 0.35 logarithm of minimal angle of resolution (logMAR) units (decimal BCVA ranged from 0.03 to 0.5). Gonioscopy showed no angle closure in any eyes. The length of time between onset of symptoms and the initial examination ranged from 1 to 12 months, with a mean of 4.6 ± 3.2 months (± standard deviation). The interval between
the onset of symptoms and vitreous surgery ranged from 1 to 30 months (mean, 7.8 months). No patient had an IOP >21 mmHg at any visit. Six patients had been diagnosed with normal-tension glaucoma and treated with topical beta-blockers or prostaglandin analogs, and the other patients were newly diagnosed with glaucomatous optic neuropathy. Unoprostone had been used in Cases 1 and 2, timolol and latanoprost in Case 4, and tafluprost in Cases 9, 10, and 11. An RNFL defect was detected stereoscopically at the inferior arcade in eight eyes, the superior arcade in one eye, and at both the superior and inferior arcades in two eyes. Fluorescein angiography was performed on seven eyes, and none of the eyes had any leakage or any hypofluorescent or hyperfluorescent lesions at the optic disc. Optical coherence tomography findings Macular retinoschisis was detected in all eyes (Figs. 1, 2, 3, 4, and 5, Table 1). Foveal detachment was detected in nine eyes (82 %), and an outer retinal hole was detected in all eyes with foveal detachment. The retinoschisis involved the outer plexiform layer, inner plexiform layer, and RNFL (Figs. 1 and 4). Two fellow eyes had retinoschisis around the optic disc but the macula was not involved (Figs. 4 and 5). PVD was not present in these eyes. Vitreoretinal adhesions at the RNFL defect were detected by OCT (Figs. 1, 4, and 5). Retinoschisis in the RNFL was connected to the retinal vessels, suggesting dehiscence of the RNFL along the retinal vessels (Figs. 1, 4, and 5). A lowreflective area that was detected above the lamina cribrosa in
Table 1 Characteristics and optical coherence tomography findings among subjects Case
Age (year)
Sex
R/L
RE (diopter)
PVD
RS
FD
ORH
Acquired pit
IOP (mmHg)
Disc cup enlargement
RNFL defect
Axial length (mm)
RS in other eye
1 2 3 4 5 6 7 8 9 10 11
63 67 68 75 72 73 60 62 75 81 71
F F M M F F F F F M F
R R R L L L R L L L L
+1.5 0 +1.0 −1.25 +2.25 −1.5 +0.25 +0.25 +0.75 IOL −2.25
− − − −* + − − − − −* −*
+ + + + + + + + + + +
− + + + + + + + + + −
− + + + + + + + + + −
− − − − − − − − − − −
11** 14* 17 8** 13 10 17 15 12** 10** 14**
+ + + + + + notch + + + +
sup + inf inf sup sup + inf inf inf inf inf inf inf inf
21.4 25.1 22.5 22.6 23.6 23.7 21.7 22.5 23.0 23.5 24.0
− − − + − − − − − − +
F = female, M = male, R = right eye, L = left eye, RE = refractive error, IOL = intraocular lens, PVD = posterior vitreous detachment, −* = PVD appeared to be present on ophthalmoscopy, but vitreous adhesion was detected with optical coherence tomography or during surgery, RS = retinoschisis, FD = foveal detachment, ORH = outer retinal hole, IOP = intraocular pressure, ** = treated with anti-glaucoma drugs, RNFL = retinal nerve fiber layer, notch = notching of the optic disc, with wedge-shaped disc cupping, sup = superior, inf = inferior, N/A = not available
Graefes Arch Clin Exp Ophthalmol
Fig. 1 Ophthalmoscopy and optical coherence tomography (OCT) images of Case 1. a: Preoperative fundus photograph of the right eye of a 63year-old woman (Case 1 in Table 1) showing macular retinoschisis (white arrowheads) and retinal nerve fiber layer (RNFL) defect (black arrowheads). The scanned OCT lines in Figs. B–F are shown as green lines. b: Horizontal OCT scan across the macula and (c) adjacent horizontal scan of B shows that the retinoschisis is located in the RNFL (white arrowheads), the outer plexiform layer (OPL), and the inner plexiform layer (IPL). The posterior vitreous cortex is attached to the retina (blue arrowheads), and a liquefied vitreous cavity can be seen above the optic disc (yellow arrowhead). Retinoschisis in the RNFL is adjacent to a retinal artery (black arrowhead). d. Oblique OCT scans along and across the nerve fiber layer defect (e, f) show three layers of retinoschisis. The
posterior vitreous cortex (blue arrowheads) is attached at the retinoschisis in the RNFL at the margin of the optic disc beneath the liquefied vitreous cavity (yellow arrowhead). The retinoschisis in the RNFL is adjacent to a retinal artery (black arrowhead). g: Postoperative fundus photograph 18 months after surgery showing a resolution of the macular retinoschisis. The RNFL defect can be seen more clearly. The scanned OCT line in Fig. 1i is shown as a green line. h. Postoperative horizontal OCT scan of the same section as Fig. 1c taken two weeks after surgery showing a resolution of retinoschisis in the RNFL (white arrowheads), but retinoschisis remains in the OPL and the IPL. i. Horizontal OCT section across the macula and the center of the optic disc shows resolution of retinoschisis in the OPL and IPL, but cystoid macular edema (black arrowheads) remains. (bar =1 mm)
the preoperative swept-source OCT image can be seen connected to the retinoschisis of the inner and outer plexiform layers (Fig. 5).
FAF images showed that the foveal detachments were hypofluorescent (Fig. 3) and outer retinal holes were hyperfluorescent. The size of these hypofluorescent and
Fig. 2 Fluorescein angiogram and pattern deviation on Humphrey field analyzer test of Case 1. a: Preoperative magnified photograph of the optic disc showing the retinal nerve fiber layer (RNFL) defect (arrowheads) and tortuosity of the vessels (arrows) at the cupped disc. b: Postoperative optical coherence tomography analysis showing a thinning of the RNFL (arrows) corresponding to the area with the RNFL defect. c: Preoperative early-phase fluorescein angiogram of the right eye shows hyperfluorescence at the temporal margin of the optic disc but no leakage. d. Postoperative pattern deviation on Humphrey field analyzer test in the right eye indicates a decrease in the threshold corresponding to the RNFL defect.
Graefes Arch Clin Exp Ophthalmol
Fig. 3 Ophthalmoscopy and fundus autofluorescence (FAF) images and optical coherence tomography (OCT) images of Case 2. a: Preoperative fundus photograph of the right eye of a 67-year-old woman (Case 2 in Table 1) showing macular retinoschisis (white arrowheads) and foveal detachment (black arrowheads), with an outer retinal hole at the fovea. A retinal nerve fiber layer (RNFL) defect (arrows) is also seen. The scanned OCT lines in Figs. 3d and 3e are shown as white lines. b. Preoperative FAF image shows hypofluorescence corresponding to the foveal detachment (arrowheads) and hyperfluorescence at the outer retinal holes (arrow). c. Magnified photograph of the right eye shows RNFL defect (arrowheads) and tortuosity of the vessels (arrow) at the cupped disc. d. Horizontal OCT scan across the macula and (e) adjacent horizontal scan of Fig. 3d show retinoschisis in the outer plexiform layer (arrows) and RNFL (black arrowhead) connected to the optic disc as well as foveal detachment, with an outer retinal hole (white arrowheads). f:
Postoperative horizontal OCT image shows a macular hole (arrows) after dehiscence of the inner retinal wall, with the outer retinal hole (arrowhead) remaining. g: Postoperative horizontal OCT image across the macula shows resolution of macular retinoschisis and foveal detachment. The optic disc cup is visibly deeper than that in the preoperative OCT image. h: Postoperative fundus photograph shows resolution of macular retinoschisis and foveal detachment. The scanned OCT line in Fig. 3g is shown as a white line. The inferior RNFL defect (arrowheads) and cupped disc (arrow) are more clearly visible than in the preoperative image. i: Postoperative FAF image shows absence of hypofluorescence at the foveal detachment and hyperfluorescence at the outer retinal hole (arrow). j: Postoperative pattern deviation on Humphrey field analyzer of the right eye demonstrating reduced thresholds corresponding to the inferior RNFL defect. (bar =1 mm)
hyperfluorescent areas decreased with resolution of the foveal detachment.
However, attachment of the vitreous cortex to the retina and optic disc was not detected preoperatively or intraoperatively in one eye (Case 5). The ILM was peeled in eight eyes (Table 2). After the vitrectomy, the retinoschisis in the RNFL resolved immediately, and the retinoschisis in the outer and the inner plexiform layers resolved later (Figs. 1 and 4). The optic disc cup and RNFL defects were more clearly visible after the resolution of macular retinoschisis (Figs. 1, 3, and 4). In the two eyes without ILM peeling, a macular hole (Case 2, Fig. 3) or a macular hole retinal detachment (Case 5) developed one month after surgery, and both were treated successfully by a second vitrectomy with ILM peeling and gas tamponade. The macular hole that developed postoperatively in one
Anatomical results A preoperative PVD was absent in 10 eyes, and in seven of these eyes, the posterior vitreous cortex was firmly attached to the temporal margin of the optic disc, as detected intraoperatively. The presence of residual vitreous cortex was confirmed with triamcinolone acetonide crystals. In three of 4 eyes in which PVD was seen preoperatively on ophthalmoscopy, residual vitreous cortex was seen intraoperatively around the optic disc. This thin vitreous cortex was also detected preoperatively in the OCT images (Figs. 4 and 5).
Graefes Arch Clin Exp Ophthalmol
eye was closed after the second vitrectomy (Case 2). In the other eye (Case 5) that developed a macular hole retinal detachment postoperatively, the retina was reattached but the macular hole was not closed. A macular hole developed in two eyes in which ILM peeling had been performed (Cases 9, 10). The macular hole in one eye was closed after sulfur hexafluoride gas injection (Case 10), but the hole in the other eye was not closed (Case 9), even after a second vitrectomy with expanded ILM peeling and gas tamponade. In one eye (Case 3) with macular retinoschisis and foveal detachment with an outer retinal hole, and in one eye (Case 11) with macular retinoschisis, fovea-sparing ILM peeling was performed around the macula to prevent the formation of a postoperative macular hole. No hole developed in these eyes after resolution of macular retinoschisis and foveal detachment.
Fig. 4 Ophthalmoscopy and optical coherence tomography (OCT) images of Case 4. a. Preoperative fundus photograph of the left eye of a 75year-old man (Case 4 in Table 1) showing macular retinoschisis and foveal detachment (white arrowheads) with outer retinal hole (black arrowheads). The scanned OCT lines in Figs. 4b and 4c are shown as green lines. b. Preoperative horizontal OCT image of the macula showing macular retinoschisis in the retinal nerve fiber layer (RNFL, black arrowheads), the inner plexiform layer, and the outer plexiform layer. Foveal detachment is present, and an outer retinal hole (white arrowheads) is present at the fovea. A lengthening of the photoreceptor outer segments around the hole can be seen. c. Preoperative horizontal OCT scan across the RNFL defect showing retinoschisis in the RNFL (white arrowheads) adjacent to the RNFL defect (blue arrowheads). The defect is located between the retinal vessels (black arrowheads) and the vitreous strand (black arrows) at the edge of the RNFL defect. d. Circular OCT scan of the optic disc in the right eye showing that retinoschisis in
The average length of time for resolution of macular retinoschisis and foveal detachment after surgery was 11 ± 3 months in the six eyes that were followed until complete resolution of the macular retinoschisis and foveal detachment, and that did not develop a macular hole or macular hole retinal detachment. Best-corrected visual acuity (BCVA) The BCVA improved significantly after vitrectomy (p = 0.004, Wilcoxon signed-rank test), and BCVA showed significant improvement in the eyes of the 10 patients who were followed for at least six months (p= 0.006). The BCVA recovered to ≥20/40 in the eyes of all six patients who were followed for at least six months and who had no postoperative complications.
the RNFL (black arrow) is located between the retinal vessels (black arrowheads) and the edge of the RNFL defect (white arrowheads). e. Circular OCT scan of the optic disc of the left eye showing that retinoschisis in the RNFL (arrow) is located adjacent to the retinal vessels (arrowheads), including the papillomacular bundle. f. Postoperative horizontal OCT image of the same area of Fig. 4b one month after surgery showing a resolution of the retinoschisis in the RNFL (arrowheads) and deeper disc cupping (arrow) at the temporal side compared to that shown in Fig. 4b. g: Magnified photograph six months after surgery showing cupped disc and the RNFL defect at the superior and inferior arcades (arrowheads) more clearly than that in Fig. 4a. h. Horizontal OCT image of the same scan as Fig. 4b taken six months after surgery, showing a resolution of retinoschisis in the RNFL (arrowheads), but the foveal detachment with defects of the photoreceptor outer segments (arrow) and retinoschisis in the inner plexiform layer remain. (bar =1 mm)
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Fig. 5 Ophthalmoscopy and optical coherence tomography (OCT) images of Case 11. a. Fundus photograph of the left eye of a 71-year-old woman (Case 11 in Table 1) shows macular retinoschisis with retinal nerve fiber layer (RNFL) defect (arrowheads). The scanned OCT lines in Figs. 5b and 5c are shown as green lines. b. Horizontal scan of Spectralis SD-OCT image across the macula and (c) oblique scan of Spectralis OCT image showing that the retinoschisis in the RNFL (white arrowheads) is connected to the retinal vessels (black arrowheads). d: Magnified photograph of the optic disc shows the RNFL defect (arrowheads) and tortuosity of the vessels (arrow) at the cupped disc. e. Oblique swept-source
OCT image shows the presence of vitreous strands (black arrowheads) at the retinal vessels. Retinoschisis in the outer plexiform layer is connected to the low-reflectivity area (yellow arrows) above the lamina cribrosa. f: Fundus photograph of the right eye with RNFL defect (arrowheads). The scanned OCT line in Fig. 5g is shown as a green line. g: Horizontal sweptsource OCT image showing retinoschisis in the RNFL (white arrowheads) from the retinal vessels (black arrowheads) in association with retinoschisis in the inner and outer plexiform layers. Retinoschisis in the inner and outer plexiform layers is connected by a low-reflectivity area (yellow arrows) above the lamina cribrosa. (bar =1 mm)
Discussion
optic neuropathy and normal IOP during the follow-up period. The locations of decreased sensitivity in the visual field tests were related to the RNFL defects and the large optic disc cups. In addition, six of the patients had already been diagnosed with normal-tension glaucoma by glaucoma specialists. Kahook et al. [19] described two cases of peripapillary retinoschisis associated with increased IOP and angleclosure glaucoma but without PVD. OCT examination of these two eyes showed a distinct splitting of the peripapillary RNFL and inner plexiform layer. One of the patients developed peripapillary retinoschisis that extended to the macula; in the other patient, the retinoschisis resolved after a decrease in IOP, but remained unresolved in the fellow eye. The authors suggested that peripapillary retinoschisis represented a unique consequence of the IOP fluctuations in patients with uncontrolled glaucoma [19]. The earlier reported cases had acute elevations of IOP from glaucoma, resulting in structural
Our patients had no obvious congenital optic disc pits or colobomas, no history of congenital ocular diseases, and no hypofluorescent lesions in the optic disc in the early phase of fluorescein angiography that became hyperfluorescent at the late phase. These changes are generally seen in eyes with congenital optic disc pits [11]. A multigenerational study of autosomal dominant-familial cavitary optic disc anomalies reported the presence of progressive optic disc cupping and multiple radial cilioretinal arteries, with normal IOP. Evidence of serous macular detachment was common [16]. We could not completely exclude the presence of congenital optic disc anomalies in the cupped discs before these eyes developed glaucomatous optic neuropathy because we had no records excluding the presence of congenital optic disc anomalies, as described [9]. However, all of the eyes had glaucomatous
Graefes Arch Clin Exp Ophthalmol Table 2 Postoperative outcomes of patients and clinical course Case
Symptomatic period (months)
Treatment
Pre-op BCVA
BCVA at the last visit
Post-op complications
Resolution of macular retinoschisis (months)
Follow-up period (months)
1 2 3 4
3 3 12 4
Phaco, Vx Phaco, Vx Phaco, Vx, ILM (fovea-sparing) Phaco, Vx, ILM
20/200 20/133 20/200 20/50
20/25 20/50 20/20 20/30
− MH − −
14 Drainage 11 12
19 26 29 12
5 6 7 8 9 10 11
8 4 4 5 6 1 1
Phaco, Vx Phaco, Vx, ILM Phaco, Vx, ILM Phaco, Vx, ILM Phaco, Vx, ILM Vx, ILM Phaco, Vx, ILM (fovea-sparing)
20/600 20/250 20/60 20/200 20/200 20/133 20/40
20/200 20/125 20/30 20/20 20/100 20/33 20/30
MHRD − − − MH MH −
Drainage Not followed 6 11 Drainage Drainage 10
78 4 15 36 30 11 12
BCVA = best-corrected visual acuity, Phaco = phacoemulsification and aspiration with intraocular lens implantation, Vx = vitrectomy, ILM = internal limiting membrane peeling, MH = macular hole, MHRD = macular hole retinal detachment, Drainage = drainage of subretinal fluid through macular hole or intentional break, Not followed = follow-up was terminated prior to resolution of macular retinoschisis
defects in the optic nerve head, which led to retinoschisis and retinal detachments similar to those seen in cases of congenital optic disc pits [6, 17, 29, 35]. Zumbro et al. [37] described cases of macular retinoschisis and foveal detachment associated with acquired optic disc cup enlargements, and they were the first to describe the efficacy of vitrectomy to resolve macular retinoschisis and foveal detachment. The eyes showed no leakage on fluorescein angiography and no vitreous traction. In one patient, resolution of macular retinoschisis and macular fluid occurred after filtering surgery for uncontrolled elevated IOP. Two patients underwent vitrectomy with intraocular gas tamponade and experienced resolution of macular fluid and improvement in vision. The authors suggested that retinoschisis was caused by leakage of vitreous fluid through fine holes in the thin tissue of the cup, which is similar to the mechanism suggested for patients with optic disc pit maculopathy [37]. Therefore, the surgical removal of vitreous traction or surgical control of IOP were able to resolve the retinal elevation and improve visual acuity, although these cases did not identify vitreous traction by ophthalmoscopy or time-domain OCT. We used spectral-domain OCT, which detected attachment of the vitreous to the area of the RNFL defect at the edge of the optic disc. After vitreous surgery, the inner retinoschisis resolved immediately, but the retinoschisis in the other layers and foveal detachment did not resolve for almost a year. In some cases, the RNFL defect was not apparent before surgery because of the inner retinoschisis in the RNFL, and the RNFL defect was more clearly visible after postoperative resolution of the inner retinoschisis. In our study, further reduction of IOP by anti-glaucoma drugs in cases of normal-tension glaucoma did not appear to reduce macular retinoschisis, as the six patients who had
already been treated with anti-glaucoma medication developed macular retinoschisis during follow-up. None of the patients experienced visual field deterioration after the resolution of macular retinoschisis. We followed the patients for several months prior to the decision to perform vitreous surgery, as postoperative resolution of macular retinoschisis does not occur for approximately 11 months, and rapid resolution of retinoschisis in the RNFL might have been the natural course of this disease. However, we are not able to predict the precise natural course of the disease. In addition, we failed to detect vitreous traction that caused the macular retinoschisis in one eye with PVD. We assume that the retinoschisis and retinal detachment, with poorer preoperative vision possibly due to long duration, had not resolved even after vitreous detachment in this eye. Further studies are needed to determine the most appropriate time for surgical intervention. Two patients had peripapillary retinoschisis in the fellow eyes. Hwang and colleagues [18] described peripapillary retinoschisis within the retinal nerve fiber, ganglion cell, and inner plexiform layers detected by OCT in 19 glaucomatous eyes. However, none of the eyes developed macular retinoschisis, and the peripapillary retinoschisis resolved in all eyes without any treatment, which suggests that transient peripapillary retinoschisis may develop asymptomatically in glaucomatous eyes. Zhao and Li [36] described a case in which macular retinoschisis developed during the course of normal-tension glaucoma. The authors posited that micro-holes in the thin retina and structural defects in the RNFL around the optic cup allowed liquid vitreous to enter the retina, resulting in retinoschisis and serous retinal detachment. Our OCT findings indicated that the clefts that allowed vitreous fluid into the intraretinal space may be located along the retinal vessels,
Graefes Arch Clin Exp Ophthalmol
and that they developed because of the thin RNFL. Vitreous traction may cause retinoschisis near the RNFL defect, and retinoschisis in the other layers and the foveal detachment develop from the seeping of fluid through the intraretinal areas. In a recent study, multiple irregularly shaped defects in the transparent membrane overlying the optic disc pits were identified histologically in an eye-bank eye with optic disc pit maculopathy [3]. A connection between the subretinal space and a schisis-like cavity in the retina adjacent to the optic pit was detected in this eye as well. However, swept-source OCT identified that the retinoschisis in the outer plexiform layer in our patients was connected to the low-reflectivity space above the lamina cribrosa, which may indicate that this type of retinoschisis was created by the entry of fluid from the arachnoid space. The perivascular spaces on the optic disc may be connected to the subarachnoid space in the same way as the Virchow–Robin spaces in the brain [5]. These spaces may have enlarged due to the fragility of the lamina cribrosa caused by the reduced number of nerve fibers in the cupped optic disc. It has been suggested that there is a turbulent flow in the porous optic disc pit sac produced by the difference between the intracranial pressure and the IOP [12]. This then increases fluid access to the intraretinal space, leading to the schisis-like separation in eyes with optic disc pit maculopathy [12]. The eyes in our study had normal IOP, and may have had greater turbulent flow in the deep optic disc cup than eyes with high IOP and less turbulent flow. The pathology of macular retinoschisis in our cases may have a different mechanism from that of peripapillary retinoschisis in eyes with an acute increase in IOP. In this work, we reported the efficacy of vitrectomy for the resolution of macular retinoschisis in eyes with enlarged optic disc cups. Four of our patients, however, developed a macular hole or macular hole retinal detachment. In optic disc pit maculopathy with foveal detachment, vitrectomy with ILM peeling can produce an excellent outcome despite the postoperative formation of a macular hole [27]. Fovea-sparing ILM peeling has been reported to protect against the development of postoperative macular holes in eyes with myopic traction maculopathy [14, 26]. We are unable to confirm this, as there were only two eyes in our study that had this procedure. We also described the efficacy of FAF imaging to indicate a recovery of the photoreceptor outer segments after resolution of macular retinoschisis and detachment. The FAF images in our cases demonstrated changes posterior to the schisis and macular detachment and corresponded to the anatomic recovery. These findings were similar to cases of optic disc pit maculopathy [13, 20]. There were limitations to this study. The number of patients was small, and the resolution of the OCT was limited such that it was not possible to identify the source of the fluid in the
retinoschisis cavity. We did not determine diurnal changes in IOP in order to diagnose normal-tension glaucoma in the patients who had not been diagnosed by a glaucoma specialist. Further studies with a larger number of patients are needed to confirm our findings. In conclusion, macular retinoschisis and foveal detachment can develop as a result of the vitreous traction near the RNFL defect and the structural fragility of the RNFL and optic disc cup in eyes with glaucomatous optic neuropathy and normal IOP. The retinoschisis can resolve spontaneously or it can be resolved with vitreous surgery to relieve the vitreous traction. Acknowledgements The authors declare that no government or nongovernment financial support was involved in the work for this submission. Contributions of authors are as follows: management, analysis, interpretation, and preparation of data (MI, YI, TR, YK, KH, DK, AH); interpretation and preparation of the manuscript (MI, YI, RT, YK, AH). The study and data accumulation were carried out with approval from the Institutional Review Board of the Kyorin University School of Medicine, and conformed to the tenets of the Declaration of Helsinki. Informed consent for the research was obtained from all patients. Disclosure The authors have no proprietary or commercial interest in any materials discussed in these reported clinical observations or this article.
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Graefes Arch Clin Exp Ophthalmol 12. Hirakata A, Inoue M, Hiraoka T, McCuen BW II (2012) Vitrectomy without laser treatment or gas tamponade for macular detachment associated with an optic disc pit. Ophthalmology 119:810–818 13. Hiraoka T, Inoue M, Ninomiya Y, Hirakata A (2010) Infrared and fundus autofluorescence imaging in eyes with optic pit maculopathy. Clin Experiment Ophthalmol 38:669–677 14. Ho TC, Chen MS, Huang JS, Shih YF, Ho H, Huang YH (2012) Foveola nonpeeling technique in internal limiting membrane peeling of myopic foveoschisis surgery. Retina 32:631–634 15. Hollander DA, Barricks ME, Duncan JL, Irvine AR (2005) Macular schisis detachment associated with angle-closure glaucoma. Arch Ophthalmol 123:270–272 16. Honkanen RA, Jampol LM, Fingert JH, Moore MD, Taylor CM, Stone EM, Alward WL (2007) Familial cavitary optic disk anomalies: clinical features of a large family with examples of progressive optic nerve head cupping. Am J Ophthalmol 143:788–794 17. Hubschman JP, Reddy S, Kaines A, Law S (2010) Nasal retinoschisis associated with glaucoma. Ophthalmic Surg Lasers Imaging. doi:10. 3928/15428877-20100215-60 18. Hwang YH, Kim YY, Kim HK, Sohn YH (2014) Effect of peripapillary retinoschisis on retinal nerve fibre layer thickness measurement in glaucomatous eyes. Br J Ophthalmol 98:669–674 19. Kahook MY, Noecker RJ, Ishikawa H, Wollstein G, Kagemann L, Wojtkowski M, Duker JS, Srinivasan VJ, Fujimoto JG, Schuman JS (2007) Peripapillary schisis in glaucoma patients with narrow angles and increased intraocular pressure. Am J Ophthalmol 143:697–699 20. Laud K, Visaetsilpanonta S, Yannuzzi LA, Spaide RF (2007) Autofluorescence imaging of optic pit maculopathy. Retina 27: 116–119 21. Lincoff H, Lopez R, Kreissig I, Yannuzzi L, Cox M, Burton T (1988) Retinoschisis associated with optic nerve pits. Arch Ophthalmol 106: 61–67 22. Lincoff H, Kreissig I (1998) Optical coherence tomography of pneumatic displacement of optic disc pit maculopathy. Br J Ophthalmol 82:367–372 23. Mavrikakis E, Lam WC (2011) Macular schisis and detachment secondary to large optic nerve head cup: a newly recognized syndrome amenable to vitrectomy. Acta Ophthalmol 89:95–96 24. Meirelles RL, Aggio FB, Costa RA, Farah ME (2005) STRATUS optical coherence tomography in unilateral colobomatous excavation
of the optic disc and secondary retinoschisis. Graefes Arch Clin Exp Ophthalmol 243:76–81 25. Schatz H, McDonald HR (1988) Treatment of sensory retinal detachment associated with optic nerve pit or coloboma. Ophthalmology 95:178–186 26. Shimada N, Sugamoto Y, Ogawa M, Takase H, Ohno-Matsui K (2012) Fovea-sparing internal limiting membrane peeling for myopic traction maculopathy. Am J Ophthalmol 154:693–701 27. Shukla D, Kalliath J, Tandon M, Vijayakumar B (2012) Vitrectomy for optic disk pit with macular schisis and outer retinal dehiscence. Retina 32:1337–1342 28. Snead MP, James N, Jacobs PM (1991) Vitrectomy, argon laser, and gas tamponade for serous retinal detachment associated with an optic disc pit: a case report. Br J Ophthalmol 75:381–382 29. Song IS, Shin JW, Shin YW, Uhm KB (2011) Optic disc pit with peripapillary retinoschisis presenting as a localized retinal nerve fiber layer defect. Korean J Ophthalmol 25:455–458 30. Spaide RF, Costa DL, Huang SJ (2003) Macular schisis in a patient without an optic disk pit optical coherence tomographic findings. Retina 23:238–240 31. Sugar HS (1962) Congenital pits in the optic disc with acquired macular pathology. Am J Ophthalmol 53:307–311 32. Tantri A, Vrabec TR, Cu-Unjieng A, Frost A, Annesley WH Jr, Donoso LA (2004) X-linked retinoschisis: a clinical and molecular genetic review. Surv Ophthalmol 49:214–230 33. Theodossiadis PG, Grigoropoulos VG, Emfietzoglou J, Theodossiadis GP (2007) Vitreous findings in optic disc pit maculopathy based on optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 245:1311–1318 34. Ugurlu S, Weitzman M, Nduaguba C, Caprioli J (1998) Acquired pit of the optic nerve: a risk factor for progression of glaucoma. Am J Ophthalmol 125:457–464 35. Yoshikawa T, Nishimura T, Minamino K, Takahashi K (2013) A long-term follow-up of peripapillary retinoschisis with optic disc hypoplasia. Int Ophthalmol 33:425–428 36. Zhao M, Li X (2011) Macular retinoschisis associated with normal tension glaucoma. Graefes Arch Clin Exp Ophthalmol 249:1255–1258 37. Zumbro DS, Jampol LM, Folk JC, Olivier MM, Anderson-Nelson S (2007) Macular schisis and detachment associated with presumed acquired enlarged optic nerve head cups. Am J Ophthalmol 144:70–74
RETINAL DISORDERS
Macular retinoschisis associated with glaucomatous optic neuropathy in eyes with normal intraocular pressure Makoto Inoue & Yuji Itoh & Tosho Rii & Yoshiyuki Kita & Kazunari Hirota & Daisuke Kunita & Akito Hirakata
Received: 24 August 2014 / Revised: 25 September 2014 / Accepted: 1 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose The purpose of this study was to evaluate the clinical features, optical coherence tomography (OCT) findings, and surgical outcomes of eyes with macular retinoschisis associated with glaucomatous optic neuropathy and normal intraocular pressure (IOP). Methods In this retrospective interventional observational study, 11 eyes of 11 patients who underwent pars plana vitrectomy for macular retinoschisis and glaucomatous optic neuropathy were studied. All eyes had a vertical cup-to-disc ratio of ≥0.7 and retinal nerve fiber layer (RNFL) defects. Intraocular pressure (IOP) was 500-nm for detection. Nine single-image frames were averaged (8.8 frames/sec) using the Automatic Real Time (ART) composite function to obtain high-quality images. The pre- and postoperative IOP was measured with a Goldmann applanation tonometer. The presence of glaucomatous optic neuropathy was diagnosed by a glaucoma specialist based on stereoscopic fundus examinations. The examinations showed the presence of an increased cup-todisc ratio, neuroretinal rim narrowing, and retinal nerve fiber layer (RNFL) defects. Gonioscopy was used to evaluate the anterior chamber angle. The visual field sensitivity (standard automated perimetry) was measured with a Humphrey field analyzer (Humphrey/Carl Zeiss Meditec, Dublin, CA) using the 30–2 Swedish interactive threshold algorithm. The results of visual field sensitivity testing were confirmed after the resolution of macular retinoschisis and detachment. The presence of an acquired optic nerve head pit with a defect of the lamina cribrosa at the cupped disc was also evaluated in the OCT images. Circumpapillary RNFL thickness was detected by OCT (OCT 4000 Cirrus-HD-OCT, Carl Zeiss Meditec, Dublin, CA; Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). Eleven eyes underwent vitreous surgery. All surgeries were performed under retrobulbar anesthesia. The surgical procedures included the creation of a PVD if one was not present, as well as both peeling and no peeling of the internal limiting membrane (ILM). Two eyes underwent fovea-sparing ILM peeling to remove the ILM except around the fovea [26]. As 10 of the patients were over the age of 60 years, cataractous lenses were extracted during the vitrectomy to avoid a reduction in postoperative visual acuity due to the cataracts. Eyes
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with a cataractous lens that affected visual acuity were excluded. The presence of PVD was determined with ophthalmoscopy and spectral-domain OCT (SD-OCT). SD-OCT was also used to detect the presence of retinoschisis, foveal detachment, or outer retinal hole, including dehiscence of the external limiting membrane (ELM) line. The axial length and bestcorrected visual acuity (BCVA) were determined preoperatively as well.
Results Preoperative clinical characteristics The demographics and clinical features of the eyes of the 11 patients with macular retinoschisis associated with glaucomatous optic neuropathy are shown in Table 1. The mean age of the patients was 69.7 ± 6.4 years, with ages ranging from 60 to 81 years. The affected eye was the right eye in four patients and the left eye in seven patients. All cases of macular retinoschisis were unilateral, but the glaucomatous optic disc cup and stereoscopic RNFL defects were present in both eyes in all patients. Ten eyes were phakic, with a mean refractive error (spherical equivalent) of +0.1 ± 1.4 diopters (D) and a range from +1.5 to −2.25 D. The preoperative BCVA was 0.86 ± 0.35 logarithm of minimal angle of resolution (logMAR) units (decimal BCVA ranged from 0.03 to 0.5). Gonioscopy showed no angle closure in any eyes. The length of time between onset of symptoms and the initial examination ranged from 1 to 12 months, with a mean of 4.6 ± 3.2 months (± standard deviation). The interval between
the onset of symptoms and vitreous surgery ranged from 1 to 30 months (mean, 7.8 months). No patient had an IOP >21 mmHg at any visit. Six patients had been diagnosed with normal-tension glaucoma and treated with topical beta-blockers or prostaglandin analogs, and the other patients were newly diagnosed with glaucomatous optic neuropathy. Unoprostone had been used in Cases 1 and 2, timolol and latanoprost in Case 4, and tafluprost in Cases 9, 10, and 11. An RNFL defect was detected stereoscopically at the inferior arcade in eight eyes, the superior arcade in one eye, and at both the superior and inferior arcades in two eyes. Fluorescein angiography was performed on seven eyes, and none of the eyes had any leakage or any hypofluorescent or hyperfluorescent lesions at the optic disc. Optical coherence tomography findings Macular retinoschisis was detected in all eyes (Figs. 1, 2, 3, 4, and 5, Table 1). Foveal detachment was detected in nine eyes (82 %), and an outer retinal hole was detected in all eyes with foveal detachment. The retinoschisis involved the outer plexiform layer, inner plexiform layer, and RNFL (Figs. 1 and 4). Two fellow eyes had retinoschisis around the optic disc but the macula was not involved (Figs. 4 and 5). PVD was not present in these eyes. Vitreoretinal adhesions at the RNFL defect were detected by OCT (Figs. 1, 4, and 5). Retinoschisis in the RNFL was connected to the retinal vessels, suggesting dehiscence of the RNFL along the retinal vessels (Figs. 1, 4, and 5). A lowreflective area that was detected above the lamina cribrosa in
Table 1 Characteristics and optical coherence tomography findings among subjects Case
Age (year)
Sex
R/L
RE (diopter)
PVD
RS
FD
ORH
Acquired pit
IOP (mmHg)
Disc cup enlargement
RNFL defect
Axial length (mm)
RS in other eye
1 2 3 4 5 6 7 8 9 10 11
63 67 68 75 72 73 60 62 75 81 71
F F M M F F F F F M F
R R R L L L R L L L L
+1.5 0 +1.0 −1.25 +2.25 −1.5 +0.25 +0.25 +0.75 IOL −2.25
− − − −* + − − − − −* −*
+ + + + + + + + + + +
− + + + + + + + + + −
− + + + + + + + + + −
− − − − − − − − − − −
11** 14* 17 8** 13 10 17 15 12** 10** 14**
+ + + + + + notch + + + +
sup + inf inf sup sup + inf inf inf inf inf inf inf inf
21.4 25.1 22.5 22.6 23.6 23.7 21.7 22.5 23.0 23.5 24.0
− − − + − − − − − − +
F = female, M = male, R = right eye, L = left eye, RE = refractive error, IOL = intraocular lens, PVD = posterior vitreous detachment, −* = PVD appeared to be present on ophthalmoscopy, but vitreous adhesion was detected with optical coherence tomography or during surgery, RS = retinoschisis, FD = foveal detachment, ORH = outer retinal hole, IOP = intraocular pressure, ** = treated with anti-glaucoma drugs, RNFL = retinal nerve fiber layer, notch = notching of the optic disc, with wedge-shaped disc cupping, sup = superior, inf = inferior, N/A = not available
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Fig. 1 Ophthalmoscopy and optical coherence tomography (OCT) images of Case 1. a: Preoperative fundus photograph of the right eye of a 63year-old woman (Case 1 in Table 1) showing macular retinoschisis (white arrowheads) and retinal nerve fiber layer (RNFL) defect (black arrowheads). The scanned OCT lines in Figs. B–F are shown as green lines. b: Horizontal OCT scan across the macula and (c) adjacent horizontal scan of B shows that the retinoschisis is located in the RNFL (white arrowheads), the outer plexiform layer (OPL), and the inner plexiform layer (IPL). The posterior vitreous cortex is attached to the retina (blue arrowheads), and a liquefied vitreous cavity can be seen above the optic disc (yellow arrowhead). Retinoschisis in the RNFL is adjacent to a retinal artery (black arrowhead). d. Oblique OCT scans along and across the nerve fiber layer defect (e, f) show three layers of retinoschisis. The
posterior vitreous cortex (blue arrowheads) is attached at the retinoschisis in the RNFL at the margin of the optic disc beneath the liquefied vitreous cavity (yellow arrowhead). The retinoschisis in the RNFL is adjacent to a retinal artery (black arrowhead). g: Postoperative fundus photograph 18 months after surgery showing a resolution of the macular retinoschisis. The RNFL defect can be seen more clearly. The scanned OCT line in Fig. 1i is shown as a green line. h. Postoperative horizontal OCT scan of the same section as Fig. 1c taken two weeks after surgery showing a resolution of retinoschisis in the RNFL (white arrowheads), but retinoschisis remains in the OPL and the IPL. i. Horizontal OCT section across the macula and the center of the optic disc shows resolution of retinoschisis in the OPL and IPL, but cystoid macular edema (black arrowheads) remains. (bar =1 mm)
the preoperative swept-source OCT image can be seen connected to the retinoschisis of the inner and outer plexiform layers (Fig. 5).
FAF images showed that the foveal detachments were hypofluorescent (Fig. 3) and outer retinal holes were hyperfluorescent. The size of these hypofluorescent and
Fig. 2 Fluorescein angiogram and pattern deviation on Humphrey field analyzer test of Case 1. a: Preoperative magnified photograph of the optic disc showing the retinal nerve fiber layer (RNFL) defect (arrowheads) and tortuosity of the vessels (arrows) at the cupped disc. b: Postoperative optical coherence tomography analysis showing a thinning of the RNFL (arrows) corresponding to the area with the RNFL defect. c: Preoperative early-phase fluorescein angiogram of the right eye shows hyperfluorescence at the temporal margin of the optic disc but no leakage. d. Postoperative pattern deviation on Humphrey field analyzer test in the right eye indicates a decrease in the threshold corresponding to the RNFL defect.
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Fig. 3 Ophthalmoscopy and fundus autofluorescence (FAF) images and optical coherence tomography (OCT) images of Case 2. a: Preoperative fundus photograph of the right eye of a 67-year-old woman (Case 2 in Table 1) showing macular retinoschisis (white arrowheads) and foveal detachment (black arrowheads), with an outer retinal hole at the fovea. A retinal nerve fiber layer (RNFL) defect (arrows) is also seen. The scanned OCT lines in Figs. 3d and 3e are shown as white lines. b. Preoperative FAF image shows hypofluorescence corresponding to the foveal detachment (arrowheads) and hyperfluorescence at the outer retinal holes (arrow). c. Magnified photograph of the right eye shows RNFL defect (arrowheads) and tortuosity of the vessels (arrow) at the cupped disc. d. Horizontal OCT scan across the macula and (e) adjacent horizontal scan of Fig. 3d show retinoschisis in the outer plexiform layer (arrows) and RNFL (black arrowhead) connected to the optic disc as well as foveal detachment, with an outer retinal hole (white arrowheads). f:
Postoperative horizontal OCT image shows a macular hole (arrows) after dehiscence of the inner retinal wall, with the outer retinal hole (arrowhead) remaining. g: Postoperative horizontal OCT image across the macula shows resolution of macular retinoschisis and foveal detachment. The optic disc cup is visibly deeper than that in the preoperative OCT image. h: Postoperative fundus photograph shows resolution of macular retinoschisis and foveal detachment. The scanned OCT line in Fig. 3g is shown as a white line. The inferior RNFL defect (arrowheads) and cupped disc (arrow) are more clearly visible than in the preoperative image. i: Postoperative FAF image shows absence of hypofluorescence at the foveal detachment and hyperfluorescence at the outer retinal hole (arrow). j: Postoperative pattern deviation on Humphrey field analyzer of the right eye demonstrating reduced thresholds corresponding to the inferior RNFL defect. (bar =1 mm)
hyperfluorescent areas decreased with resolution of the foveal detachment.
However, attachment of the vitreous cortex to the retina and optic disc was not detected preoperatively or intraoperatively in one eye (Case 5). The ILM was peeled in eight eyes (Table 2). After the vitrectomy, the retinoschisis in the RNFL resolved immediately, and the retinoschisis in the outer and the inner plexiform layers resolved later (Figs. 1 and 4). The optic disc cup and RNFL defects were more clearly visible after the resolution of macular retinoschisis (Figs. 1, 3, and 4). In the two eyes without ILM peeling, a macular hole (Case 2, Fig. 3) or a macular hole retinal detachment (Case 5) developed one month after surgery, and both were treated successfully by a second vitrectomy with ILM peeling and gas tamponade. The macular hole that developed postoperatively in one
Anatomical results A preoperative PVD was absent in 10 eyes, and in seven of these eyes, the posterior vitreous cortex was firmly attached to the temporal margin of the optic disc, as detected intraoperatively. The presence of residual vitreous cortex was confirmed with triamcinolone acetonide crystals. In three of 4 eyes in which PVD was seen preoperatively on ophthalmoscopy, residual vitreous cortex was seen intraoperatively around the optic disc. This thin vitreous cortex was also detected preoperatively in the OCT images (Figs. 4 and 5).
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eye was closed after the second vitrectomy (Case 2). In the other eye (Case 5) that developed a macular hole retinal detachment postoperatively, the retina was reattached but the macular hole was not closed. A macular hole developed in two eyes in which ILM peeling had been performed (Cases 9, 10). The macular hole in one eye was closed after sulfur hexafluoride gas injection (Case 10), but the hole in the other eye was not closed (Case 9), even after a second vitrectomy with expanded ILM peeling and gas tamponade. In one eye (Case 3) with macular retinoschisis and foveal detachment with an outer retinal hole, and in one eye (Case 11) with macular retinoschisis, fovea-sparing ILM peeling was performed around the macula to prevent the formation of a postoperative macular hole. No hole developed in these eyes after resolution of macular retinoschisis and foveal detachment.
Fig. 4 Ophthalmoscopy and optical coherence tomography (OCT) images of Case 4. a. Preoperative fundus photograph of the left eye of a 75year-old man (Case 4 in Table 1) showing macular retinoschisis and foveal detachment (white arrowheads) with outer retinal hole (black arrowheads). The scanned OCT lines in Figs. 4b and 4c are shown as green lines. b. Preoperative horizontal OCT image of the macula showing macular retinoschisis in the retinal nerve fiber layer (RNFL, black arrowheads), the inner plexiform layer, and the outer plexiform layer. Foveal detachment is present, and an outer retinal hole (white arrowheads) is present at the fovea. A lengthening of the photoreceptor outer segments around the hole can be seen. c. Preoperative horizontal OCT scan across the RNFL defect showing retinoschisis in the RNFL (white arrowheads) adjacent to the RNFL defect (blue arrowheads). The defect is located between the retinal vessels (black arrowheads) and the vitreous strand (black arrows) at the edge of the RNFL defect. d. Circular OCT scan of the optic disc in the right eye showing that retinoschisis in
The average length of time for resolution of macular retinoschisis and foveal detachment after surgery was 11 ± 3 months in the six eyes that were followed until complete resolution of the macular retinoschisis and foveal detachment, and that did not develop a macular hole or macular hole retinal detachment. Best-corrected visual acuity (BCVA) The BCVA improved significantly after vitrectomy (p = 0.004, Wilcoxon signed-rank test), and BCVA showed significant improvement in the eyes of the 10 patients who were followed for at least six months (p= 0.006). The BCVA recovered to ≥20/40 in the eyes of all six patients who were followed for at least six months and who had no postoperative complications.
the RNFL (black arrow) is located between the retinal vessels (black arrowheads) and the edge of the RNFL defect (white arrowheads). e. Circular OCT scan of the optic disc of the left eye showing that retinoschisis in the RNFL (arrow) is located adjacent to the retinal vessels (arrowheads), including the papillomacular bundle. f. Postoperative horizontal OCT image of the same area of Fig. 4b one month after surgery showing a resolution of the retinoschisis in the RNFL (arrowheads) and deeper disc cupping (arrow) at the temporal side compared to that shown in Fig. 4b. g: Magnified photograph six months after surgery showing cupped disc and the RNFL defect at the superior and inferior arcades (arrowheads) more clearly than that in Fig. 4a. h. Horizontal OCT image of the same scan as Fig. 4b taken six months after surgery, showing a resolution of retinoschisis in the RNFL (arrowheads), but the foveal detachment with defects of the photoreceptor outer segments (arrow) and retinoschisis in the inner plexiform layer remain. (bar =1 mm)
Graefes Arch Clin Exp Ophthalmol
Fig. 5 Ophthalmoscopy and optical coherence tomography (OCT) images of Case 11. a. Fundus photograph of the left eye of a 71-year-old woman (Case 11 in Table 1) shows macular retinoschisis with retinal nerve fiber layer (RNFL) defect (arrowheads). The scanned OCT lines in Figs. 5b and 5c are shown as green lines. b. Horizontal scan of Spectralis SD-OCT image across the macula and (c) oblique scan of Spectralis OCT image showing that the retinoschisis in the RNFL (white arrowheads) is connected to the retinal vessels (black arrowheads). d: Magnified photograph of the optic disc shows the RNFL defect (arrowheads) and tortuosity of the vessels (arrow) at the cupped disc. e. Oblique swept-source
OCT image shows the presence of vitreous strands (black arrowheads) at the retinal vessels. Retinoschisis in the outer plexiform layer is connected to the low-reflectivity area (yellow arrows) above the lamina cribrosa. f: Fundus photograph of the right eye with RNFL defect (arrowheads). The scanned OCT line in Fig. 5g is shown as a green line. g: Horizontal sweptsource OCT image showing retinoschisis in the RNFL (white arrowheads) from the retinal vessels (black arrowheads) in association with retinoschisis in the inner and outer plexiform layers. Retinoschisis in the inner and outer plexiform layers is connected by a low-reflectivity area (yellow arrows) above the lamina cribrosa. (bar =1 mm)
Discussion
optic neuropathy and normal IOP during the follow-up period. The locations of decreased sensitivity in the visual field tests were related to the RNFL defects and the large optic disc cups. In addition, six of the patients had already been diagnosed with normal-tension glaucoma by glaucoma specialists. Kahook et al. [19] described two cases of peripapillary retinoschisis associated with increased IOP and angleclosure glaucoma but without PVD. OCT examination of these two eyes showed a distinct splitting of the peripapillary RNFL and inner plexiform layer. One of the patients developed peripapillary retinoschisis that extended to the macula; in the other patient, the retinoschisis resolved after a decrease in IOP, but remained unresolved in the fellow eye. The authors suggested that peripapillary retinoschisis represented a unique consequence of the IOP fluctuations in patients with uncontrolled glaucoma [19]. The earlier reported cases had acute elevations of IOP from glaucoma, resulting in structural
Our patients had no obvious congenital optic disc pits or colobomas, no history of congenital ocular diseases, and no hypofluorescent lesions in the optic disc in the early phase of fluorescein angiography that became hyperfluorescent at the late phase. These changes are generally seen in eyes with congenital optic disc pits [11]. A multigenerational study of autosomal dominant-familial cavitary optic disc anomalies reported the presence of progressive optic disc cupping and multiple radial cilioretinal arteries, with normal IOP. Evidence of serous macular detachment was common [16]. We could not completely exclude the presence of congenital optic disc anomalies in the cupped discs before these eyes developed glaucomatous optic neuropathy because we had no records excluding the presence of congenital optic disc anomalies, as described [9]. However, all of the eyes had glaucomatous
Graefes Arch Clin Exp Ophthalmol Table 2 Postoperative outcomes of patients and clinical course Case
Symptomatic period (months)
Treatment
Pre-op BCVA
BCVA at the last visit
Post-op complications
Resolution of macular retinoschisis (months)
Follow-up period (months)
1 2 3 4
3 3 12 4
Phaco, Vx Phaco, Vx Phaco, Vx, ILM (fovea-sparing) Phaco, Vx, ILM
20/200 20/133 20/200 20/50
20/25 20/50 20/20 20/30
− MH − −
14 Drainage 11 12
19 26 29 12
5 6 7 8 9 10 11
8 4 4 5 6 1 1
Phaco, Vx Phaco, Vx, ILM Phaco, Vx, ILM Phaco, Vx, ILM Phaco, Vx, ILM Vx, ILM Phaco, Vx, ILM (fovea-sparing)
20/600 20/250 20/60 20/200 20/200 20/133 20/40
20/200 20/125 20/30 20/20 20/100 20/33 20/30
MHRD − − − MH MH −
Drainage Not followed 6 11 Drainage Drainage 10
78 4 15 36 30 11 12
BCVA = best-corrected visual acuity, Phaco = phacoemulsification and aspiration with intraocular lens implantation, Vx = vitrectomy, ILM = internal limiting membrane peeling, MH = macular hole, MHRD = macular hole retinal detachment, Drainage = drainage of subretinal fluid through macular hole or intentional break, Not followed = follow-up was terminated prior to resolution of macular retinoschisis
defects in the optic nerve head, which led to retinoschisis and retinal detachments similar to those seen in cases of congenital optic disc pits [6, 17, 29, 35]. Zumbro et al. [37] described cases of macular retinoschisis and foveal detachment associated with acquired optic disc cup enlargements, and they were the first to describe the efficacy of vitrectomy to resolve macular retinoschisis and foveal detachment. The eyes showed no leakage on fluorescein angiography and no vitreous traction. In one patient, resolution of macular retinoschisis and macular fluid occurred after filtering surgery for uncontrolled elevated IOP. Two patients underwent vitrectomy with intraocular gas tamponade and experienced resolution of macular fluid and improvement in vision. The authors suggested that retinoschisis was caused by leakage of vitreous fluid through fine holes in the thin tissue of the cup, which is similar to the mechanism suggested for patients with optic disc pit maculopathy [37]. Therefore, the surgical removal of vitreous traction or surgical control of IOP were able to resolve the retinal elevation and improve visual acuity, although these cases did not identify vitreous traction by ophthalmoscopy or time-domain OCT. We used spectral-domain OCT, which detected attachment of the vitreous to the area of the RNFL defect at the edge of the optic disc. After vitreous surgery, the inner retinoschisis resolved immediately, but the retinoschisis in the other layers and foveal detachment did not resolve for almost a year. In some cases, the RNFL defect was not apparent before surgery because of the inner retinoschisis in the RNFL, and the RNFL defect was more clearly visible after postoperative resolution of the inner retinoschisis. In our study, further reduction of IOP by anti-glaucoma drugs in cases of normal-tension glaucoma did not appear to reduce macular retinoschisis, as the six patients who had
already been treated with anti-glaucoma medication developed macular retinoschisis during follow-up. None of the patients experienced visual field deterioration after the resolution of macular retinoschisis. We followed the patients for several months prior to the decision to perform vitreous surgery, as postoperative resolution of macular retinoschisis does not occur for approximately 11 months, and rapid resolution of retinoschisis in the RNFL might have been the natural course of this disease. However, we are not able to predict the precise natural course of the disease. In addition, we failed to detect vitreous traction that caused the macular retinoschisis in one eye with PVD. We assume that the retinoschisis and retinal detachment, with poorer preoperative vision possibly due to long duration, had not resolved even after vitreous detachment in this eye. Further studies are needed to determine the most appropriate time for surgical intervention. Two patients had peripapillary retinoschisis in the fellow eyes. Hwang and colleagues [18] described peripapillary retinoschisis within the retinal nerve fiber, ganglion cell, and inner plexiform layers detected by OCT in 19 glaucomatous eyes. However, none of the eyes developed macular retinoschisis, and the peripapillary retinoschisis resolved in all eyes without any treatment, which suggests that transient peripapillary retinoschisis may develop asymptomatically in glaucomatous eyes. Zhao and Li [36] described a case in which macular retinoschisis developed during the course of normal-tension glaucoma. The authors posited that micro-holes in the thin retina and structural defects in the RNFL around the optic cup allowed liquid vitreous to enter the retina, resulting in retinoschisis and serous retinal detachment. Our OCT findings indicated that the clefts that allowed vitreous fluid into the intraretinal space may be located along the retinal vessels,
Graefes Arch Clin Exp Ophthalmol
and that they developed because of the thin RNFL. Vitreous traction may cause retinoschisis near the RNFL defect, and retinoschisis in the other layers and the foveal detachment develop from the seeping of fluid through the intraretinal areas. In a recent study, multiple irregularly shaped defects in the transparent membrane overlying the optic disc pits were identified histologically in an eye-bank eye with optic disc pit maculopathy [3]. A connection between the subretinal space and a schisis-like cavity in the retina adjacent to the optic pit was detected in this eye as well. However, swept-source OCT identified that the retinoschisis in the outer plexiform layer in our patients was connected to the low-reflectivity space above the lamina cribrosa, which may indicate that this type of retinoschisis was created by the entry of fluid from the arachnoid space. The perivascular spaces on the optic disc may be connected to the subarachnoid space in the same way as the Virchow–Robin spaces in the brain [5]. These spaces may have enlarged due to the fragility of the lamina cribrosa caused by the reduced number of nerve fibers in the cupped optic disc. It has been suggested that there is a turbulent flow in the porous optic disc pit sac produced by the difference between the intracranial pressure and the IOP [12]. This then increases fluid access to the intraretinal space, leading to the schisis-like separation in eyes with optic disc pit maculopathy [12]. The eyes in our study had normal IOP, and may have had greater turbulent flow in the deep optic disc cup than eyes with high IOP and less turbulent flow. The pathology of macular retinoschisis in our cases may have a different mechanism from that of peripapillary retinoschisis in eyes with an acute increase in IOP. In this work, we reported the efficacy of vitrectomy for the resolution of macular retinoschisis in eyes with enlarged optic disc cups. Four of our patients, however, developed a macular hole or macular hole retinal detachment. In optic disc pit maculopathy with foveal detachment, vitrectomy with ILM peeling can produce an excellent outcome despite the postoperative formation of a macular hole [27]. Fovea-sparing ILM peeling has been reported to protect against the development of postoperative macular holes in eyes with myopic traction maculopathy [14, 26]. We are unable to confirm this, as there were only two eyes in our study that had this procedure. We also described the efficacy of FAF imaging to indicate a recovery of the photoreceptor outer segments after resolution of macular retinoschisis and detachment. The FAF images in our cases demonstrated changes posterior to the schisis and macular detachment and corresponded to the anatomic recovery. These findings were similar to cases of optic disc pit maculopathy [13, 20]. There were limitations to this study. The number of patients was small, and the resolution of the OCT was limited such that it was not possible to identify the source of the fluid in the
retinoschisis cavity. We did not determine diurnal changes in IOP in order to diagnose normal-tension glaucoma in the patients who had not been diagnosed by a glaucoma specialist. Further studies with a larger number of patients are needed to confirm our findings. In conclusion, macular retinoschisis and foveal detachment can develop as a result of the vitreous traction near the RNFL defect and the structural fragility of the RNFL and optic disc cup in eyes with glaucomatous optic neuropathy and normal IOP. The retinoschisis can resolve spontaneously or it can be resolved with vitreous surgery to relieve the vitreous traction. Acknowledgements The authors declare that no government or nongovernment financial support was involved in the work for this submission. Contributions of authors are as follows: management, analysis, interpretation, and preparation of data (MI, YI, TR, YK, KH, DK, AH); interpretation and preparation of the manuscript (MI, YI, RT, YK, AH). The study and data accumulation were carried out with approval from the Institutional Review Board of the Kyorin University School of Medicine, and conformed to the tenets of the Declaration of Helsinki. Informed consent for the research was obtained from all patients. Disclosure The authors have no proprietary or commercial interest in any materials discussed in these reported clinical observations or this article.
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