Posterior Vitreous Detachment As Observed by Wide-Angle OCT Imaging

Posterior Vitreous Detachment as Observed by Wide-Angle OCT Imaging

Mayuka Tsukahara, OD,1,* Keiko Mori, MD,1 Peter L. Gehlbach, MD, PhD,2 Keisuke Mori, MD, PhD1,3,4,*

Purpose: Posterior vitreous detachment (PVD) plays an important role in vitreoretinal interface disorders. Historically, observations of PVD using OCT have been limited to the macular region. The purpose of this study is to image the wide-angle vitreoretinal interface after PVD in normal subjects using montaged OCT images. Design: An observational cross-sectional study. Participants: A total of 144 healthy eyes of 98 normal subjects aged 21 to 95 years (51.422.0 [mean standard deviation]). Methods: Montaged images of horizontal and vertical OCT scans through the fovea were obtained in each subject. Main Outcome Measures: Montaged OCT images. Results: By using wide-angle OCT, we imaged the vitreoretinal interface from the macula to the periphery. PVD was classified into 5 stages: stage 0, no PVD (2 eyes, both aged 21 years); stage 1, peripheral PVD limited to paramacular to peripheral zones (88 eyes, mean age 38.916.2 years, mean standard deviation); stage 2, perifoveal PVD extending to the periphery (12 eyes, mean age 67.98.4 years); stage 3, peripapillary PVD with persistent vitreopapillary adhesion alone (7 eyes, mean age 70.911.9 years); stage 4, complete PVD (35 eyes, mean age 75.110.1 years). All stage 1 PVDs (100%) were observed in the paramacular to peripheral region where the vitreous gel adheres directly to the cortical vitreous and retinal surface. After progression to stage 2 PVD, the area of PVD extends posteriorly to the perifovea and anteriorly to the periphery. Vitreoschisis was observed in 41.2% at PVD initiation (stage 1a). Conclusions: Whereas prior work suggests that PVD originates in the perifoveal region and after the sixth decade, our observations demonstrate that (1) PVD first appears even in the third decade of life and gradually appears more extensively throughout life; (2) more than 40% of eyes without fundus diseases at their PVD initiation are associated with vitreoschisis; and (3) PVD is first noted primarily in the paramacular-peripheral region where vitreous gel adheres to the retinal surface and is noted to be more extensive in older ages to ultimately involve the fovea. Ophthalmology 2018;125:1372-1383 ª 2018 by the American Academy of Ophthalmology

Posterior vitreous detachment (PVD) is one of the more years. Moreover, PVD origination is now believed to occur universally experienced and potentially important normal in the perifoveal macula.10e14 However, the OCT obser- ocular events. It is often the underlying cause of a patient’s vations leading to these present descriptions were limited symptoms of flashes and floaters in the eye. Posterior to the macular region as is provided in standard OCT vitreous detachment also plays a key role in the patho- studies. genesis of multiple visually significant vitreoretinal inter- Our group has recently reported a novel imaging strategy face disorders, such as macular hole,1e3 premacular and method that uses wide-angle images of OCT of the membrane with pucker (so-called epiretinal membrane),4,5 whole vitreoretinal interface extended from the macula to vitreomacular traction syndrome,3,6 retinal detachments,7,8 the periphery. With this novel wide-field imaging technique, vitreous hemorrhages,8 and others. Posterior vitreous we reported baseline images of the vitreous, retina, and detachment manifests as vitreous gel liquefaction and choroid;15 normative data describing regional differences weakening of vitreoretinal adhesion.3,9 Therefore, it is in- and aging changes in the macula and more peripheral tegral to pathology occurring at the vitreoretinal interface. retina (Omata et al, Abstract no. 1770, presented in the Historically, PVD has been considered an acute event Association of Research in Vision and Ophthalmology, initiated by an abrupt break developing in the posterior May 3, 2010, Fort Lauderdale, FL); and morphologic vitreous cortex. The timing of such vitreous separation in relationships between these structures during the the setting of PVD was believed to be age related and development and progression of macular holes.16,17 More- occurred after the sixth decade of life.7,10 Recent reports over, the feasibility of this montaging imaging technique has using OCT and ultrasonography suggest that age-related now been replicated by other study groups.18e20 The pur- PVD may be less of an acute event and more of an insid- pose of the present study is to describe the first appearance ious and slowly progressive condition evolving over many and subsequent extent of PVD at various ages of

1372 ª 2018 by the American Academy of Ophthalmology https://doi.org/10.1016/j.ophtha.2018.02.039 Published by Elsevier Inc. ISSN 0161-6420/18

Downloaded for Anonymous User (n/a) at Kaiser Permanente from ClinicalKey.com by Elsevier on October 03, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. Tsukahara et al Posterior Vitreous Detachment physiologic PVD throughout the entire vitreoretinal inter- Conventional OCT imaging is typically limited to the macular e face from the macula to the periphery using wide-angle zone, ranging from 7 to 12 mm.10 14 Our montaging technique 15 OCT imaging. allows evaluation of images that are on the order of 25 to 36 mm. Incidence of PVD in each quadrant of each stage was statistically evaluated by the chi-square test. The association of known Methods PVD risk factors, including age, female gender, and myopic refraction, was analyzed with polytomous logistic regression Patients and Study Design analysis. Statistical data analysis was performed with commercially available software (Bell Curve for Excel ver. 2.14, SSRI, Tokyo, This is an observational cross-sectional study. A total of 144 eyes Japan). P values less than 0.05 were considered statistically of 98 healthy normal volunteers underwent a wide-angle montage significant. of OCT images of their entire viewable vitreoretinal interface. The investigation adhered to all of the tenets of the Declaration of Helsinki. This study was approved by the institutional review Results board of the Saitama Medical University (approval no. 11-041-01) On the basis of the findings observed in montaged OCT images, and the Ethics Committee of International University of Health and fi Welfare (approval no. 13-B-225). Subjects were enrolled from PVD was classi ed into the following 5 stages: stage 0, no PVD August 2011 to December 2012 in the Saitama Medical University present (2 eyes, both aged 21 years); stage 1, peripheral PVD and from October 2016 to April 2017 in the International Uni- limited to paramacular, peripheral or from paramacular to peripheral zones (88 eyes, mean age 38.916.2 years, mean standard versity of Health and Welfare. The composition of the subject e population was 60 female and 38 male participants, ranging in age deviation, median 34.5, range 21 73); stage 2, perifoveal PVD expanding to the periphery (12 eyes, mean age 67.98.4 years, from 21 to 95 years (51.4 22.0, mean standard deviation) e (Table 1). All subjects were examined by indirect ophthalmoscopy, median 68.5, range 56 85); stage 3, peripapillary PVD with slit-lamp biomicroscopic examination, refraction, and best- persistent vitreopapillary adhesion alone (7 eyes, mean age 70.911.9 years, median 72, range 56e85); stage 4, complete corrected visual acuity testing. Excluded were eyes with present or past vitreous-retina-choroid disease, hyperopia >þ3.0 diopters PVD (35 eyes, mean age 75.1 10.1 years, median 77, range 59e95). Stage 1 was divided into 2 subcategories: stage 1a, pe- or myopia exceeding 5.0 diopters, and advanced cataract that fl may affect the image quality. ripheral PVD with multilayered linear hyperre ective lines or interposed reflective material between retina and vitreous (34 eyes, mean age 29.413.0 years, median 23, range 21e65); stage 1b, Spectral-Domain and Swept-Source OCT peripheral PVD without interposed material between retina and All OCT examinations were performed through a dilated pupil vitreous (54 eyes, mean age 44.9 15.5 years, median, 44.5, range, e using commercially available spectral-domain OCT (Spectralis, 21 73 years) (Table 1). The mean age of occurrence for each stage Heidelberg Engineering, Vista, CA) or swept-source OCT (DRI increased, commensurate with progression of the stage of PVD. OCT Triton plus, Topcon, Tokyo, Japan). Standardized horizontal and vertical vitreoretinal sections through the fovea were collected Stage 0 for each subject. All scans with swept-source OCT were obtained In all 144 eyes examined in these age groups and without other by pulling back to focus on the vitreous. The retinochoroidal layers ocular pathology, only 2 eyes (1.4%) had no PVD in all 4 quad- were positioned inferiorly on the images screen to obtain maximum 21 rants. In these eyes, the perifoveal retina and macular choroid were imaging depth into the vitreous and vitreoretinal interface. To the thickest regions. Both retinal and choroidal thickness decreased enhance visualization of the vitreous image, contrast was toward the periphery. In both eyes granular hyper-reflections, adjusted by the planimetric image-editing system, enhanced vit- e mainly in the posterior cortical vitreous, were noticed (Fig 1). reous visualization.22 24 To examine the morphologic features of the entire posterior vitreous cortex and the vitreoretinal interface, Stage 1a wide-angle montage OCT images from the macula to the periphery (approximately to the equator) were obtained as previously Thirty-four eyes (23.6% of all eyes examined) had stage 1a PVD: e described.15 17 Montaged images were assembled using picture- peripheral PVD with multilayered linear hyperreflective lines editing software (Photoshop version 5.5, Adobe, San Jose, CA). (Figs 2 and 3) or interposed material (Fig 3) between the retina and

Table 1. Subject Age, Refraction, and Posterior Vitreous Detachment Stages

PVD Stage Subject Age, yrs Refraction (Mean ± SD) 01a1b234All 20e29 2.21.7 2 (5.6) 25 (69.4) 9 (25.0) 0 0 0 36 (100) 30e39 2.21.9 0 3 (20.0) 12 (80.0) 0 0 0 15 (100) 40e49 0.90.7 0 2 (12.5) 13 (81.3) 0 0 1 (6.3) 16 (100) 50e59 0.51.4 0 2 (13.3) 8 (53.3) 3 (20) 1 (6.7) 1 (6.7) 15 (100) 60e69 þ0.151.4 0 2 (7.4) 10 (37.0) 5 (18.5) 2 (7.4) 8 (29.6) 27 (100) 70e79 þ0.31.5 0 0 2 (10.5) 3 (15.8) 2 (10.5) 12 (63.2) 19 (100) 80- þ0.32.0 0 0 0 1 (6.3) 2 (12.5) 13 (81.3) 16 (100) Total 0.81.9 2 (1.4) 34 (23.6) 54 (37.5) 12 (8.3) 7 (4.9) 35 (24.3) 144 (100)

PVD ¼ posterior vitreous detachment; SD ¼ standard deviation. Data are expressed as the number of eyes (% of entire group).

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Figure 1. Montage images of en face fundus photographs (A), horizontal (B) and vertical (C) vitreous-retina-choroid cross-sections obtained with OCT in an eye (21-year-old female) with stage 0 posterior vitreous detachment (PVD). A highly magnified image of an inset in B, C is shown in D, E, respectively. In all 144 eyes examined, only 2 eyes had no PVD. There were no obvious alterations in retinochoroidal structure. In both 2 eyes noted were granular hyper- reflections mainly in the posterior cortical vitreous (arrows). the vitreous. Posterior vitreous cortex separation at this time is area of macular vitreous liquefaction, where vitreous gel adheres meager but is obviously present, as evidenced by separation of directly to the retina (Figs 2 and 3). vitreous and retinal surfaces on imaging. Frequently observed were granular hyper-reflections, present mainly in the posterior Stage 1b cortical vitreous (23 eyes, 67.6% of all eyes with stage 1a PVD) and vitreoschisis (Figs 2 and 3, 14 eyes, 41.2%). All stage 1a PVD Fifty-four eyes (37.5% of all eyes examined) had stage 1b PVD, originated in the midperipheral or peripheral region outside of the well-defined peripheral PVD without any interposed materials.

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Figure 2. Montaged images of en face fundus photographs (A), horizontal (B) and vertical (C) cross-sections in an eye (24-year-old male) with stage 1a posterior vitreous detachment (PVD). There is no PVD in the horizontal cross-section (B), but obviously present in superior and inferior quadrants (C, arrows). A highly magnified image of an inset in C is shown in E. Posterior vitreous cortex is separated from the retinal surface and unraveled with lamellar configuration associated with granular hyper-reflection. This lamellar separation of posterior vitreous cortex, known as vitreoschisis is frequently seen in stage 1 PVD. Montaged images of vertical (D) cross-section in another eye (26-year-old male) with stage 1a PVD. A highly magnified image of an inset in D is shown in F. Posterior vitreous cortex is disentangled similarly. Every PVD originates in the midperipheral or peripheral region outside of the area of macular vitreous liquefaction, where vitreous gel adheres directly to the retina (C, D, arrows). Arrowheads (in C, D) indicate the posterior edge of the PVD.

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Figure 3. Montaged images of en face fundus photographs (A), horizontal (B) and vertical (C) cross-sections in an eye (23-year-old female) with stage 1a posterior vitreous detachment (PVD). A highly magnified image of an inset in B, C is shown in E, F, respectively. In the horizontal cross-section, there are premacular lacuna and the area of Martegiani (B, E). PVD is evident in the nasal and temporal midperiphery, and in septum papillo-maculae, in between these liquefactions (arrows in E). Posterior vitreous cortex is unraveled in a lamellar fashion similarly but more distinctly than those shown in Fig 2. Arrows in F indicate a single well-defined layer analogous to typical PVD seen in stage 1b, 2, and 3 PVD (Figs 4e6) among subtle multiple layers and granular hyper- reflection. Montaged images of vertical (D) cross-section in another eye (21-year-old female) with stage 1a PVD. A highly magnified image of an inset in D is shown in G. An otherwise imperceptible posterior vitreous cortex detachment is evident with interposed reflective material between retina and vitreous (arrows in G) associated with granular hyper-reflection. Arrowheads (in E, G) indicate the posterior edge of the PVD. Every PVD originates outside of the area of macular vitreous liquefaction and the area of Martegiani, where vitreous gel adheres directly to the retina. 1376

Stage 1b PVD is characterized by clean and clear separation of the vitreous liquefaction, where the vitreous gel was directly adherent posterior vitreous cortex from the retinal surface. Granular hyper- to the retina (Figs 4 and 5). reﬂection was frequently observed (40 eyes, 67.6% of all eyes with stage 1b PVD), and vitreoschisis was present less frequently Stages 2, 3, and 4 (13 eyes, 24.0%) than in stage 1a. In 2 eyes, we had occasion to observe a small dehiscence of posterior vitreous cortex with vit- Twelve eyes (8.3% of all eyes examined) had stage 2 PVD, peri- reous herniation. All stage 1b PVDs were located in the mid- foveal PVD with persistent adhesion of the posterior vitreous to the peripheral or peripheral region, outside of the area of macular papilla and fovea. Typical evolution of PVDs is to move

Figure 4. Montaged images of en face fundus photographs (A), horizontal (B) and vertical (C) cross-sections in an eye (36-year-old female) with stage 1b posterior vitreous detachment (PVD); well-deﬁned PVD without any interposed materials are presented. A highly magniﬁed image of an inset in B is shown in D and of an inset in C is shown in E. In the horizontal cross-section there are large premacular bursa and the area of Martegiani (B, D). Stage 1b PVD is evident in the nasal quadrant, and in septum papillo-maculae, in between these liquefactions (arrows in B). In the vertical section, the obvious stage 1b PVD extends further in superior quadrant with wavy vitreous surface potentially suggesting mobility (arrows in C). Note the onion-like lamellar structure in the vitreous body (asterisk in C) and small dehiscence of posterior vitreous cortex with vitreous herniation (arrowheads in E).

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Figure 5. Montaged images of en face fundus photographs (A), horizontal (B), and vertical (C) cross-sections in an eye (34-year-old female) with stage 1b posterior vitreous detachment (PVD). A highly magniﬁed image of an inset in C is shown in D. Arrows in B indicate narrow but distinct PVD without interposed materials. Montaged images of en face fundus photographs (E), horizontal (F) and vertical (H) cross-sections in an eye (35-year-old male) with stage 1b PVD. A highly magniﬁed image of an inset in F is shown in G and of an inset in H is shown in I. The area of PVD expands more posteriorly and anteriorly. Arrowheads (in D, G, I) indicate the posterior edge of the PVD.

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Downloaded for Anonymous User (n/a) at Kaiser Permanente from ClinicalKey.com by Elsevier on October 03, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. Tsukahara et al Posterior Vitreous Detachment posteriorly to the perifoveal region and anteriorly to the periphery adheres directly to the posterior cortical vitreous and retinal sur- close to the equator (Fig 6A). Seven eyes (4.9%) had stage 3 PVD, face. In progressing to more advanced stages of PVD, extension of peripapillary PVD with persistent adhesion of the posterior vitreoretinal separation was noted more posteriorly nearer the vitreous to the papilla (Fig 6B). Thirty-five eyes (24.5%) had perifoveal region and anteriorly nearer the periphery. We were able stage 4 PVD, complete PVD (Fig 6C). Granular hyper-reflection to identify more vitreoretinal separation with the montaged OCT was evident in 5 (41.7%) of all eyes with stage 2 PVD and in 1 technique out to near the equator. Stage 1a PVD was evident in the (14.3%) of all eyes with stage 3 PVD, but was not present in stage superior quadrant of 30 eyes (88.2% of all stage 1a PVD), in the 4 PVD because the posterior vitreous cortex separation was located inferior quadrant of 29 eyes (85.3%), in the nasal quadrant of 25 too anteriorly to image. Vitreoschisis was not frequently observed eyes (73.5%), and in the temporal quadrant of 10 eyes (29.4%). (only 2 eyes with stage 2 PVD, 1 in stage 3 and none in stage 4). Stage 1b PVD was evident in the superior quadrant of 51 eyes The mean age of the patient at each stage of vitreous separation (94.4% of all eyes with stage 1b PVD), in the inferior quadrant of increased commensurate with progression of the stage of PVD. 44 eyes (81.5%), in the nasal quadrant of 47 eyes (87.0%), and in This finding is consistent with the age-related occurrence and the temporal quadrant of 40 eyes (74.1%). There was a significant progression of PVD. difference in the stage1a and 1b PVD quadrant of origin (Fig 7) (P ¼ 2.410 8 and 2.810 2, respectively, chi-square test). Posterior Vitreous Detachment Stages and The prevalence of granular hyper-reflection decreased with Additional Findings progressive stages of PVD (stage 0, 100%; stage 1, 71.6%; stage 2, 41.7%; stage 3, 14.3%; stage 4, not available). Vitreoschisis was All PVDs (100%) were first noted in the paramacular, mid- observed in 30.7% of stage 1 PVD eyes. This was more frequently peripheral, or peripheral region. This site of initiation was outside noted in stage 1a than stage 1b PVDs (41.2% and 24.0%, of the area of macular vitreous liquefaction, where the vitreous gel respectively). Observation of a small dehiscence (<100 mm) of

Figure 6. Montaged images of vitreoretinal cross-sections in eyes with stage 2 (68-year-old female, A), stage 3 (60-year-old female, B) and stage 4 (61-year- old male, C) posterior vitreous detachment (PVDs). Stage 2, perifoveal PVD; stage 3, peripapillary PVD; stage 4, complete PVD.

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Figure 7. Geographic distribution of stage 1 posterior vitreous detachment (PVD). Incidence of stage 1a PVD is high in the order of superior > inferior > nasal > temporal quadrant (P ¼ 2.4108). Incidence of stage 1b PVD is still highest in the superior quadrant, but the significance is lower (P ¼ 2.8102) than stage 1a PVD. All stage 1 PVDs (100%) originated and located in the midperipheral or peripheral region outside of the area of macular vitreous liquefaction, where vitreous gel adheres directly to the vitreoretinal interface. posterior vitreous cortex with or without vitreous herniation was even in the third decade of life and seen more extensively present in 2 eyes (3.7% of stage 1b PVD eyes). One was in the and frequently in later life; (2) more than 40% of eyes perifoveal region as shown in Figure 4E, and the other was in the without vitreous-retina-choroid pathologies at their first peripapillary region (Table 2). appearance of PVD are associated with vitreoschisis Risk factors (age, female gender, myopic refraction) for more (splitting of the posterior vitreous cortex); and (3) the extensive PVD were analyzed with age-adjusted/multivariate- fi adjusted polytomous logistic regression. Among these factors, location of rst appearance of PVD is primarily in the age alone was associated with PVD progression (Table 3) extramacular-peripheral vitreous where vitreous gel is (P ¼ 3.331011). directly adherent to the posterior cortical vitreous and the retinal surface. Historically and clinically, PVD in the normal eye is Discussion often considered an acute event occurring with an abrupt break in the posterior vitreous cortex leading to mechanical Using an established technique of montaging OCT images, collapse and separation of the degenerate vitreous away we have documented differences in the vitreoretinal inter- from the retina. The timing of this event is known to be age face noted at different ages with respect to PVD. As a result related, often occurring after the sixth decade.7,10 A recent of observations made during the course of this study, we are OCT study reported a mean age of first onset of PVD of now able to report potentially significant findings: (1) In approximately 55 years.14 However, our study of the otherwise normal eyes, it is usual for PVD to be first noted extramacular and peripheral vitreous strongly suggests that

Table 2. Posterior Vitreous Detachment Stages and Incidence of OCT Findings

Granular Hyper-reﬂection Vitreoschisis (Lamellar Separation Posterior Vitreous Cortex Stage No. in the Peripheral Vitreous of Posterior Vitreous Cortex) Dehiscence with Vitreous Herniation 0 2 2 (100) 0 (0) 0 (0) 1 88 63 (71.6) 27 (30.7) 2 (2.3) 1a 34 23 (67.6) 14 (41.2) 0 (0) 1b 54 40 (74.1) 13 (24.0) 2 (3.7) 2 12 5 (41.7) 2 (16.7) 0 (0) 3 7 1 (14.3) 1 (14.3) 0 (0) 435NA NA NA

NA ¼ not available. Data are expressed as the number of eyes (% of entire group).

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Table 3. Multivariate-Adjusted Probabilities of Risk Factors for Posterior Vitreous Detachment Progression

Age-Adjusted Multivariate-Adjusted Risk Factors Chi-Square P* Chi-Square P* Age (yrs) NA NA 48.2 3.331011 Gender (male ¼ 0, female ¼ 1) 2.88 0.23 2.47 0.29 Refraction (emmetropia ¼ 0, myopia ¼ 1) 4.60 0.10 4.19 0.12

Myopia, 5 diopters (D) refraction <3 D; emmetropia, 3Drefraction þ3D. NA ¼ not available. *Polytomous logistic regression analysis. the first appearance of PVD is significantly earlier, and that Because age, female gender, and myopic refraction were PVD progression is of a more chronic nature rather than an reported to be associated with PVD,38e41 association of these acute event. In the present patient population, the mean age risk factors with PVD stages was analyzed with polytomous of those with stage 1a PVD is 29.4 years and of those with logistic regression. Among these factors, age alone was stage 1b is 44.9 years. Most subjects had initial significantly associated with more extensive PVD. Although manifestations of PVD in the third decade of life (94%). It our data failed to demonstrate the association of female seems clear that this discrepancy is due to the inability of gender and myopic refraction with PVD, it is inappropriate to conventional OCT imaging protocols to observe the early conclude that the effect of these risk factors plays no role in extramacular-peripheral origins of PVD. Ultrasonography the first appearance and subsequent extent of PVD. There are is an alternative modality to evaluate both posterior and several differences, including study design, sample size, peripheral vitreous. Some studies demonstrated shallow races, and refractive range of myopia, in this current study and PVD using B-scan ultrasonography.25e27 A major strength other reports.38e41 Further study is warranted to replicate and of ultrasound in visualizing the vitreous is its ability to determine the effect of these risk factors. image vitreous dynamics in real-time. However, the major Whereas much of the present and past literature and disadvantage of ultrasonography is its lower resolution. contemporary textbooks describe a macular or perifoveal Typical axial resolutions at 12 MHz are 130 mm, and lateral origin to PVD,10e13,29,42 our observations clearly resolutions are 800 mm.28 The fine structure of vitreoretinal demonstrate that the first manifestations of PVD occur interface delineated in this study is on the order of 10 mm primarily in the midperipheral to peripheral region. Only and is well suited to OCT visualization. In contrast, the 2 eyes of the 2 youngest female participants (both aged 21 major disadvantages of OCT are its narrow range of years) had no evidence of PVD among 144 eyes exam- observation, formerly limited to the macular zone, and the ined. In eyes with stage 1a PVD, posterior cortical relative difficulty in examining real-time vitreous move- vitreous is slightly separated from the retina but clearly ment. Therefore, it is strategic to recognize and use each of has interposed material, which is unambiguously different these imaging modalities as complementary studies in than that of stage 0 PVD. Similar interposed material evaluating vitreous structure and function. between the retina and the posterior cortical vitreous was Now possible is a detailed study of a much larger portion also described in the recent observations of young of the posterior vitreous cortex that clearly demonstrates that volunteers while demonstrating the capability of high- 43 the first detected manifestation of PVD, as demonstrated in resolution OCT. In eyes with stage 1b PVD, posterior stage 1 PVD, is the frequent occurrence of vitreoschisis cortical vitreous detached clearly and widely from the (lamellar separation of posterior vitreous cortex; 41.2% in retinal surface without any interposed materials. In these stage 1a and 24.0% in stage 1b). Vitreoschisis resulting from eyes with stage 1 PVD, there was not yet obvious PVD anomalous PVD has been proposed to leave the outer layer in the macular region. Statistical analysis demonstrated of the posterior vitreous cortex attached to the retina.29e35 that stage 1 PVD occurs predominantly in the superior There are several reports describing such residual vitreous quadrant, but other quadrants are also involved. This cortex on the retinal surface during triamcinolone acetonide- phenomenon may in part be due to gravitational forces assisted vitreous surgery in eyes with rhegmatogenous that act on the superior vitreous body as a force directed retinal detachment. The incidence of residual vitreous cortex away from the retina in the upright position. was between 60% and 70%.36,37 OCT studies have found Alternatively, there may be a lesser vitreoretinal vitreoschisis in 53% of eyes with full-thickness macular adhesion superiorly or other contributing factors. After holes and 42% of eyes with macular pucker.32,34 Kishi et al5 PVD is first noted in youth, with increasing age reported with scanning electron microscopic observations vitreoretinal separation is seen more posteriorly toward that 44% of autopsy eyes with spontaneous PVD were the macula and more anteriorly toward the periphery. associated with vitreous cortex remnants on the retinal Anterior extension is often noted before posterior surface. Our observations demonstrate that the prevalence extension, providing a potential explanation for retinal of vitreoschisis in eyes without vitreous-retina-choroid pa- tears occurring with attached posterior vitreous. Again, thologies is 41.2%; a similar incidence was observed in the because of the limited range of conventional OCT study of autopsy eyes without retinal diseases.5 observation, prior reports have not been able to study

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Downloaded for Anonymous User (n/a) at Kaiser Permanente from ClinicalKey.com by Elsevier on October 03, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. Ophthalmology Volume 125, Number 9, September 2018 the sites where PVD is first noted with micron 9. Sebag J. Age-related differences in the human vitreoretinal resolution.10e14 interface. Arch Ophthalmol. 1991;109:966e971. Vitreous liquefaction has long been considered integral 10. Johnson MW. Posterior vitreous detachment: evolution and e to the pathogenesis of PVD.3,9 It is well known that the role in macular disease. Retina. 2012;32(suppl):S174 S178. volume of the solid phase of vitreous gel decreases and that 11. Johnson MW. Perifoveal vitreous detachment and its macular 29 complications. Trans Am Ophthalmol Soc. 2005;103:537e567. the liquid phase of vitreous increases with aging. Firm 12. Uchino E, Uemura A, Ohba N. Initial stages of posterior vitreous vitreoretinal adhesions occur at the vitreous base, the optic detachment in healthy eyes of older persons evaluated by optical disk, the fovea, and along the retinal blood vessels. It is coherence tomography. Arch Ophthalmol. 2001;119:1475e1479. important to appreciate that adherence of the vitreous over 13. Johnson MW. Posterior vitreous detachment: evolution and the macula is a broad rather than point-like adhesion.9,44 complications of its early stages. Am J Ophthalmol. 2010;149: Regarding tractional forces, the rotational forces of the eye 371e382. wall during ocular saccades are transmitted to the vitreous 14. Itakura H, Kishi S. Evolution of vitreomacular detachment in body via attachments to adjacent structures.42 In the macular healthy subjects. JAMA Ophthalmol. 2013;131:1348e1352. fi 15. Mori K, Kanno J, Gehlbach PL. Retinochoroidal region, large lique ed lacuna develop and are known as fi bursa premacularis or posterior precortical vitreous morphology described by wide- eld montage imaging of 45,46 spectral domain optical coherence tomography. Retina. pockets. In the present investigation, all stage 1 PVDs 2016;36:375e384. originated in the midperipheral or peripheral region. This is 16. Mori K, Kanno J, Gehlbach PL. Montage images of spectral- outside of the area of macular vitreous liquefaction, where domain optical coherence tomography in eyes with idiopathic the vitreous gel is directly adherent to the vitreoretinal macular holes. Ophthalmology. 2012;119:2600e2608. interface. Because of the liquefied premacular structure, 17. Mori K, Gehlbach PL, Kishi S. Posterior vitreous mobility dynamic forces occurring with ocular saccades are trans- delineated by tracking of optical coherence tomography im- mitted less directly to the macula from the posterior vitreous ages in eyes with idiopathic macular holes. Am J Ophthalmol. cortex. The present findings when synthesized with prior 2015;159:1132e1141. fi work suggest that dynamic forces with ocular saccades may 18. Carrai P, Pichi F, Bonsignore F, et al. Wide- eld spectral potentially contribute to the pathophysiology of PVD, as domain-optical coherence tomography in central serous cho- rioretinopathy. Int Ophthalmol. 2015;35:167e171. well as vitreous liquefaction and vitreoretinal interface 19. Pichi F, Carrai P, Bonsignore F, et al. Wide-field spectral domain deterioration. The extent to which this allows the gifted optical coherence tomography. Retina. 2015;35:2584e2592. specialized extracellular matrix to protect the macula from 20. Choudhry N, Golding J, Manry MW, Rao RC. 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Footnotes and Financial Disclosures

Originally received: October 20, 2017. HUMAN SUBJECTS: Human subjects, human-derived materials, or hu- Final revision: February 12, 2018. man medical records were part of this study protocol. All studies adhered to Accepted: February 20, 2018. the tenets of the Declaration of Helsinki. This study was approved by the Available online: April 6, 2018. Manuscript no. 2017-2409. Institutional Review Board of the Saitama Medical University (approval no. 1 Department of Ophthalmology, International University of Health and 11-041-01) and the Ethics Committee of the International University of Welfare Hospital, Nasu-Shiobara, Tochigi, Japan. Health and Welfare (approval no. 13-B-225). 2 Wilmer Eye Institute, Johns Hopkins University School of Medicine, No animal subjects were used in this study. Baltimore, Maryland. Author Contributions: 3 Department of Ophthalmology, Saitama Medical University, Iruma, Sai- Conception and design: Gehlbach, Mori tama, Japan. Data collection: Tsukahara, Mori 4 Department of Ophthalmology, International University of Health and Analysis and interpretation: Tsukahara, Mori, Mori Welfare School of Medicine, Nasu-Shiobara, Tochigi, Japan. Obtained funding: N/A *Both Mrs. Tsukahara and Dr. Mori are equal contributors. Overall responsibility: Gehlbach, Mori Financial Disclosure(s): The author(s) have made the following disclosure(s): K.M.: Consultant and Abbreviations and Acronyms: PVD ¼ grants/grants pending Santen Pharmaceutical; Lecture fees Alcon posterior vitreous detachment. Pharmaceutical, Bayer; Patents NIPRO. Correspondence: Supported in part by a grant-in-aid for scientiﬁc research (15K10879) from Keisuke Mori, MD, PhD, Department of Ophthalmology, International the Ministry of Education, Culture and Science in Japan (K.M.), Research University of Health and Welfare School of Medicine, 537-3 Iguchi, Nasu- to Prevent Blindness (New York, NY), and gifts by the J. Willard and Alice Shiobra, Tochigi 329-2763, Japan. E-mail: [email protected]; S. Marriott Foundation, the Gale Trust, Herb Ehlers, Bill Wilbur, Mr. and [email protected]. Mrs. Rajandre Shaw, Helen Nassif, and Ronald Stiff (P.L.G.).

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