CLINICAL SCIENCES. Effect of Partial Posterior Vitreous Detachment on Retinal Nerve Fiber Layer Thickness as Measured by Optical Coherence Tomography

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1 CLNCAL CENCE Effect of Partial Posterior Vitreous Detachment on Retinal Nerve Fiber Layer Thickness as Measured by Optical Coherence Tomography Priti Batta, MD; Harry M. Engel, MD; Anurag hrivastava, MD; Katherine Freeman, DrPH; Umar Mian, MD Objective: To evaluate the effect of partially attached posterior vitreous detachments (ppvds) at the optic disc on retinal nerve fiber layer (RNFL) thickness as measured by optical coherence tomography. Methods: A retrospective study was conducted using stored tratus optical coherence tomography scans of patients with suspected glaucoma from January 3 to eptember 6 at the Montefiore Medical Center, Bronx, New York. All scans were evaluated for vitreous attachments at the disc and were divided into control (without ppvd) and ppvd groups. The RNFL thickness was compared using the fast RNFL protocol. Patients were defined as glaucoma suspects based on clinical findings of either glaucomatous-appearing optic discs or elevated intraocular pressure. All study patients had normal Humphrey visual fields. Results: A total of 11 eyes from 11 patients were included; 59 were in the ppvd group and 51 were controls. Partial PVD was found in 4% of the glaucoma suspects. The mean RNFL thickness of eyes with ppvd was significantly broader than that of controls (11.6 µm vs 95.6 µm, respectively; P.1). The average RNFL thickness of each quadrant was greater in the ppvd group than in the control group, with statistically significant differences in superior and inferior quadrants (P.1 and P=.1, respectively). Conclusions: More than one-third of this population of glaucoma suspects had a ppvd, indicating that this is a common phenomenon. The results suggest that RNFL thicknesses are greater in patients with ppvd than in controls. This may indicate a limitation of using RNFL thickness as a criterion for evaluating glaucomatous damage in patients with ppvd. Arch Ophthalmol. 21;128(6): Author Affiliations: Henkind Eye nstitute (Dr Batta) and Departments of Ophthalmology and Visual ciences (Drs Batta, Engel, hrivastava, and Mian) and Epidemiology and Population Health (Dr Freeman), Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York. Dr Batta is now with the Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts. THE DAGNO OF GLAUcoma is generally established by detecting characteristic visual field defects in association with visible alterations in the surface contour of the optic nerve and elevation of the intraocular pressure. A substantial minority of retinal ganglion cells may be lost before a change in appearance of the optic disc can be discerned. 1 High-resolution retinal images obtained by optical coherence tomography (OCT) can be used to quantitatively assess retinal nerve fiber layer (RNFL) thickness. 2-4 Because thinning of the RNFL precedes ophthalmoscopically visible alteration in the cup-disc ratio, OCT has the potential to support a diagnosis of glaucoma at an early stage. 5-8 High-resolution OCT provides reproducible visualization of the vitreoretinal interface. Partially attached posterior vitreous detachment (ppvd) appears as a distinct curvilinear signal extending from the retinal surface into the vitreous cavity. 4 Our preliminary observations based on OCT studies in eyes with ppvd suggest that the RNFL is notably thicker at points of vitreous attachment, presumably due to traction exerted by the vitreous. Greater depth of the RNFL, associated with ppvd, may undermine the utility of OCT in diagnosing early glaucomatous change in patients with ppvds. We performed a retrospective cross-sectional analysis to investigate the effect of ppvds on RNFL measurements acquired by OCT. METHOD UBJECT This retrospective, observational study was approved by the Montefiore Medical Center nstitutional Review Board and was compliant with the tenets of the Declaration of Helsinki (REPRNTED) ARCH OPHTHALMOL / VOL 128 (NO. 6), JUNE Downloaded From: on 8/22/ American Medical Association. All rights reserved.

2 (1964). The OCT scans were selected consecutively from an alphabetized list of stored patient images (from January 3 to eptember 6) at the Henkind Eye nstitute, Montefiore Medical Center, Bronx, New York. cans were eligible for inclusion in the study if the patient had undergone 2 or more fast RNFL scans for both eyes (on different days) and at least 1 of these scans was performed in the randomly chosen 6-month period of January 1, 6, to July 1, 6. cans were included in the ppvd group if at least 1 area of vitreous attachment was clearly visible at the peripapillary vitreoretinal interface. n the ppvd group, a ppvd was noted in either eye or both eyes. For the few patients with ppvd in both eyes, 1 eye was randomly selected for the study. The control group consisted of eyes with no discernible ppvd on any OCT image. All scans included in the study were of patients having a diagnosis of suspected glaucoma based on either a suspicious optic nerve in the study eye (group 1) or ocular hypertension (group 2). Group 1 patients included those with a cup-disc ratio greater than.5, interocular asymmetry of the cup-disc ratio greater than.2, or thinning or notching of the neuroretinal rim. Group 2 patients had 2 consecutive intraocular pressure measurements greater than 25 mm Hg, measured via applanation tonometry (corrected for central corneal thickness), and also showed normal and symmetrical optic nerves. All study patients had undergone a Humphrey visual field test within the specified 6-month period and were found to have either a normal visual field or only nonspecific and nonprogressive visual field defects in the study eye. Patients were excluded if the Humphrey visual field test results were unreliable (defined as 33% fixation loss, a false-positive response 33%, and a false-negative response 33%). cans with an average RNFL thickness less than 8 µm were also excluded, even if visual fields were intact, to preclude inadvertent inclusion of cases with early glaucomatous damage. Patients with a history of laser treatment for retinal disease or vitrectomy were also ineligible. The control and ppvd groups were not age matched. We recorded age, ethnicity, and sex. OCT TECHNQUE All OCT images were acquired with the tratus OCT (Carl Zeiss Meditec, nc, Dublin, California) by a trained technician. mages were obtained using the standard technique for the fast RNFL protocol, which analyzes RNFL thickness based on 3 circular scans of the peripapillary RNFL. (The aiming circle used by this protocol was set at a default of 3.4 mm in diameter and was manually centered on the optic disc.) The RNFL thickness, calculated by averaging the 3 scans to determine means in the 4 quadrants as well as average thickness, was generated automatically by the tratus OCT software. cans included in the study fulfilled the following criteria: the fundus image was clear with a visible scan circle centered on the optic disc, color distribution was even and dense throughout the scan, and the RNFL borders appeared to be accurately detected by the OCT algorithm. TATTCAL ANALY Descriptive statistics are presented as means and standard deviations for continuous, normally distributed variables and as relative frequencies for rank order or categorical variables. Differences between ppvd and control groups with regard to continuous variables were tested for significance using t tests for independent samples, and those of ppvd/control groups and subgroups group 1 (suspicious disc)/group 2 (ocular hypertension) were tested for significance with analysis of variance. Associations with categorical variables were tested using 2 or Fisher exact tests. Associations between continuous variables and age were derived using Pearson correlation coefficients, and multiple linear regression analysis was used to control for differences in groups due to age. One-way and 2-way analyses of variance were performed to identify differences among subsets. All analyses were conducted with A version 9.1 statistical software (A nstitute, nc, Cary, North Carolina) at =.5 using 2-tailed tests. REULT A total of 1368 patients had OCT fast RNFL scans at the Montefiore Medical Center in the 6-month period from January 1, 6, to July 1, 6. Of these, 541 were found to have ppvd present on at least 1 scan for either eye, indicating a prevalence rate of 4% in this population. Generally, the vitreous was separated nasally and temporally (Figure 1 and Figure 2). n eyes harboring ppvd, attachments were noted superiorly in 66% and inferiorly in 75%. A total of 11 eyes of 11 patients with suspected glaucoma were included in our analysis. Fifty-nine of these were in the ppvd group and 51 were controls (showing no ppvd). This latter group included patients with intact vitreous, complete vitreous detachment, or an indeterminate vitreoretinal interface. n the subgroup analysis, group 1 (suspicious discs) included 33 eyes with ppvd and 29 control eyes. Group 2 (ocular hypertension) comprised 26 eyes with ppvd and 22 control eyes. The mean RNFL thickness of eyes with ppvd was significantly increased compared with that of controls (11.6 µm vs 95.6 µm, respectively; P.1). The average RNFL thickness of each quadrant was greater in the ppvd group than in the control group, with statistically significant differences in the superior and inferior quadrants (P.1 and P=.1, respectively). Maximum RNFL thicknesses for superior and inferior quadrants were significantly higher in the ppvd group than in controls (both P.1). Maximum-minimum RNFL thickness was also higher in the ppvd group than in controls (P.1). No significant differences among the ppvd group and controls were recognized in the temporal or nasal quadrants (Table 1). ndividuals in the control groups were significantly older (mean difference, 11.2 years; 95% confidence interval, ; P.1), but the age differences were insufficient to discount the variance in RNFL thickness when analyzed using linear regression models controlling for age (P.1). Analyses with ethnicity and sex as covariates also failed to reduce the significance of the difference in RNFL thickness between eyes with ppvd and controls (P.1) (Table 2). Multiple linear regression evaluating both the influence of ppvd and the clinical status (suspicious discs vs ocular hypertension), controlling for age, confirmed the thickness difference between control eyes and ppvd eyes for all measurements (P.2) except those made in the nasal and temporal quadrants (Table 3). There was little or no evidence of a differential effect of ppvd on eyes with suspicious discs vs those with ocular hypertension (Table 3, tests of interaction). No significant differences were found in RNFL thickness in the temporal or nasal quadrants in either the collective analysis or the subgroup analysis. (REPRNTED) ARCH OPHTHALMOL / VOL 128 (NO. 6), JUNE Downloaded From: on 8/22/ American Medical Association. All rights reserved.

3 A B T N N T OD (n = 3) O (n = 3) OD-O max/max max/max max/tavg max/tavg max/navg Maximum-minimum max max avg avg Average thickness Figure 1. Bilateral, partially attached posterior vitreous detachment in patient 1. A, canned optical coherence tomographic images from the right eye (left panel) and left eye (right panel) showing superior and inferior vitreous attachments (arrows). B, Retinal nerve fiber layer (RNFL) thickness measurements showing abruptly thickened nerve fiber layers corresponding to the vitreous detachments. indicates superior; T, temporal; N, nasal;, inferior; max, inferior quadrant maximum; max, superior quadrant maximum; Tavg, temporal quadrant average; Navg, nasal quadrant average; avg, superior quadrant average; avg, inferior quadrant average; solid line, right eye; and dashed line, left eye. COMMENT n our review of more than 1 optic nerve OCT scans performed to assess the RNFL, ppvd was recognized in 4% of eyes. n most cases of ppvd, the vitreous detached from the nasal and temporal quadrants but remained adherent in the superior and inferior quadrants. Eyes of glaucoma suspects harboring ppvd showed a statistically significantly thicker RNFL with respect to control eyes, and the RNFL thickening was most pronounced in the superior and inferior quadrants. Our study was a retrospective analysis using stored OCT scans. We did not study normal eyes. The number of variables in the groups was reduced by limiting the prescreening diagnosis to suspected glaucoma with no defects on automated visual field testing. The sample sizes had adequate power to analyze variance between the control and ppvd groups. Although our groups were not matched for age, ethnicity, and sex, these factors were evaluated and were not responsible for the variance in study and control scans. We did not record axial length, which may play a role in RNFL thickness. High myopia (REPRNTED) ARCH OPHTHALMOL / VOL 128 (NO. 6), JUNE Downloaded From: on 8/22/ American Medical Association. All rights reserved.

4 A B T N nferior Temporal N T OD (n = 3) O (n = 3) OD-O max/max max/max max/tavg max/tavg max/navg Maximum-minimum max max avg avg Average thickness Figure 2. Unilateral, partially attached posterior vitreous detachment in patient 2 (right eye, with superior and inferior vitreous attachments). A, canned optical coherence tomographic images of the right eye (left panel) and left eye (right panel). Arrows indicate the partially attached posterior vitreous detachment. B, Retinal nerve fiber layer (RNFL) thickness measurements showing thickening of the nerve fiber layer corresponding to the vitreous attachment in the right eye as well as the difference in all parameters compared with the left eye. indicates superior; T, temporal; N, nasal;, inferior; max, inferior quadrant maximum; max, superior quadrant maximum; Tavg, temporal quadrant average; Navg, nasal quadrant average; avg, superior quadrant average; avg, inferior quadrant average; solid line, right eye; and dashed line, left eye. is associated with a thinner RNFL. 9 These data were not available in our retrospective study. t is unlikely that the disparity in RNFL thickness measurements could be attributed to other variables. The average age was considerably younger (by 11.2 years) in those with ppvds compared with the control group. This may be best explained by considering the natural history of PVD. As an individual ages, complete PVD is more likely to develop. Our controls included individuals with either no PVD or complete PVD in the peripapillary region. Normative data suggest that there is an average thinning in RNFL thickness of.2 to.3 µm per year. However, the difference in the RNFL thickness between eyes with ppvd and controls was considerably higher than could be explained by the age difference. 7 Greater variability was seen in the subgroup analysis than in the overall statistical review. A 2-factor analysis of variance demonstrated that in general, the subgroups behaved similarly to the collective measurements. The control groups for group 1 (glaucoma suspects with enlarged or asymmetric cup-disc ratios) and group 2 (glaucoma suspects with normal nerves and ocular hyperten- (REPRNTED) ARCH OPHTHALMOL / VOL 128 (NO. 6), JUNE Downloaded From: on 8/22/ American Medical Association. All rights reserved.

5 Table 1. Retinal Nerve Fiber Layer Thickness in Eyes With Partially Attached Posterior Vitreous Detachment vs Control Eyes a Variable Controls, Mean (D) (n=51) ppvd, Mean (D) (n=59) Mean Difference (95% C) P Value Mean RNFL thickness 95.6 (9.9) 11.6 (8.8) 6. (2.5 to 9.6).1 Maximum-minimum (18.7) (18.9).1 uperior quadrant maximum (19.6) (2.5) 13.4 (5.8 to 21.1).1 nferior quadrant maximum (2.3) (22.2) 15.5 (7.4 to 23.6).1 uperior quadrant average 12.1 (18.9) 132. (16.4) 11.9 (5.2 to 18.6).1 nferior quadrant average (17.2) (15.9) 1.5 (4.3 to 16.8).1 Nasal quadrant average 78.4 (16.3) 83.5 (21.5) 5.1 ( 12.4 to 2.2).17 Temporal quadrant average 66.2 (12.2) 62.8 (14.4) 3.3 ( 1.7 to 8.4).2 Abbreviations: C, confidence interval; ppvd, partially attached posterior vitreous detachment; RNFL, retinal nerve fiber layer. a The control group and the ppvd group each include group 1 (the diagnosis of suspected glaucoma was based on a suspicious optic nerve in the study eye) and group 2 (the diagnosis of suspected glaucoma was based on ocular hypertension). Table 2. Age, Ethnicity, and ex a No. (%) ppvd (n=59) Controls (n=51) Characteristic Group 1 (n=33) Group 2 (n=26) Group 1 (n=29) Group 2 (n=22) Ethnicity Hispanic 6 (18) 9 (34) 9 (31) 3 (14) Black 19 (7) 13 (5) 12 (41) 14 (64) White 2 (6) 3 (12) 5 (17) 4 (18) Asian 1 (4) 2 (7) 1 (5) Unknown 6 (18) 1 (3) ex Male 7 (21) 7 (27) 1 (34) 8 (36) Female 2 (6) 19 (73) 18 (62) 14 (64) Unknown 6 (19) 1 (4) Age, mean (D) 64. (9.4) 67.7 (1.2) 76.7 (8.7) 78.5 (11.6) Unknown, No. (%) 2 (6) Abbreviation: ppvd, partially attached posterior vitreous detachment. a Group 1 indicates that the diagnosis of suspected glaucoma was based on a suspicious optic nerve in the study eye; group 2, the diagnosis of suspected glaucoma was based on ocular hypertension. Table 3. Two-way Analysis of Variance for ubgroups 1 and 2 a Variable RNFL Thickness, Mean (D), µm Group 1 Group 2 Control (n=29) ppvd (n=33) Control (n=22) ppvd (n=26) P Value for nteraction P Value for Main Effect, ppvd vs Controls Mean RNFL thickness 93.8 (9.9) 12. (8.8) 98. (9.6) 11.1 (9.1) Maximum-minimum (19.) (2.2) (18.3) (17.3).98.1 uperior quadrant maximum (19.8) (2.9) 154. (18.7) (2.8).36.2 nferior quadrant maximum (21.1) (22.4) 149. (19.7) (22.) uperior quadrant average (19.) (16.3) 126. (17.4) (16.9).3.2 nferior quadrant average (18.2) (15.6) (15.4) (16.9) Nasal quadrant average 8.3 (16.9) 83.8 (18.5) 75.9 (15.4) 84. (25.5) Temporal quadrant average 64.3 (11.5) 61. (11.2) 68.6 (12.8) 63.4 (15.7).14.1 Abbreviations: ppvd, partially attached posterior vitreous detachment; RNFL, retinal nerve fiber layer. a Group 1 indicates that the diagnosis of suspected glaucoma was based on a suspicious optic nerve in the study eye; group 2, the diagnosis of suspected glaucoma was based on ocular hypertension. There are significant differences in maximum-minimum, superior quadrant maximum, and temporal quadrant average between ppvd and controls, with the thicknesses in the ppvd group greater than those in controls in all cases. With regard to superior quadrant average, the interaction between ppvd/controls and those with/without ocular hypertension was significant, indicating that the control group with suspicious cupping yielded a significantly lower mean superior quadrant average than the control group 2 and a significantly lower mean superior quadrant average than either of the ppvd groups. sion) were generally similar except for the superior quadrant average (Table 3). This comparability was maintained when the groups were controlled for age (except for the superior quadrant average). The explanation for the variation in the subgroups and especially in the superior quadrant is not obvious. (REPRNTED) ARCH OPHTHALMOL / VOL 128 (NO. 6), JUNE Downloaded From: on 8/22/ American Medical Association. All rights reserved.

6 That ppvd is associated with a thicker RNFL is not unexpected. Examples of alterations of the vitreoretinal interface causing changes in retinal and optic nerve structure that may be registered by OCT have been noted in eyes undergoing vitrectomy for diabetic macular edema, vitreomacular traction syndrome, and vitreopapillary traction We found that ppvd is associated with increased RNFL thickness, especially in superior and inferior quadrants, and is most likely explained by traction from the adherent vitreous on these quadrants. (Two-thirds of eyes with ppvd showed attachments in the superior or inferior quadrants of the nerve.) Given our finding that more than one-third of patients undergoing optic nerve OCT scanning have ppvd, this effect may have important implications for OCT use in diagnosing glaucoma. ubmitted for Publication: October 8, 7; final revision received eptember 1, 9; accepted October 5, 9. Correspondence: Umar Mian, MD, Department of Ophthalmology and Visual ciences, Montefiore Medical Center, 111 E 21 t, Bronx, NY 1467 (umian@montefiore.org). Financial Disclosure: None reported. REFERENCE 1. Quigley HA, Addicks EM, Green WR. Optic nerve damage in human glaucoma, : quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol. 1982;(1): Huang D, wanson EA, Lin CP, et al. Optical coherence tomography. cience. 1991;254(535): chuman J, Pedut-Kloizman T, Hertzmark E, et al. Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology. 1996;13(11): Williams ZY, chuman J, Gamell L, et al. Optical coherence tomography measurement of nerve fiber layer thickness and the likelihood of a visual field defect. Am J Ophthalmol. 2;134(4): ommer A, Katz J, Quigley HA, et al. Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol. 1991;19(1): chuman J, Hee MR, Puliafito CA, et al. Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Arch Ophthalmol. 1995;113(5): Budenz DL, Chang RT, Huang X, Knighton RW, Tielsch JM. Reproducibility of retinal nerve fiber thickness measurements using the stratus OCT in normal and glaucomatous eyes. nvest Ophthalmol Vis ci. 5;46(7): Paunescu LA, chuman J, Price L, et al. Reproducibility of nerve fiber thickness, macular thickness, and optic nerve head measurements using tratus OCT. nvest Ophthalmol Vis ci. 4;45(6): Leung CK, Mohamed, Leung K, et al. Retinal nerve fiber layer measurements in myopia: an optical coherence tomography study. nvest Ophthalmol Vis ci. 6; 47(12): Yamamoto T, Hitani K, Tsukahara, et al. Early postoperative retinal thickness changes and complications after vitrectomy for diabetic macular edema. Am J Ophthalmol. 3;135(1): Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol. 1995;119(1): Massin P, Duguid G, Erginay A, Haouchine B, Gaudric A. Optical coherence tomography for evaluating diabetic macular edema before and after vitrectomy. Am J Ophthalmol. 3;135(2): Cabrera, Katz A, Margalit E. Vitreopapillary traction: cost-effective diagnosis by optical coherence tomography. Can J Ophthalmol. 6;41(6): This Month in Archives of Ophthalmology This Month s Free Article Healthy Diets and the ubsequent Prevalence of Nuclear Cataract in Women Early-Release Article Final Visual Acuity Results in the Early Treatment for Retinopathy of Prematurity tudy ign Up for Free Table of Contents Alerts Topic Collection Alerts R Feeds View Last Month s Most Viewed Articles Most ent Articles Most Viewed Collections upplementary Online-Only Content Proprioceptive Transient Elevation of Ptotic Eyelid and Lacrimation in Congenital Third Nerve Palsy: The Monosynaptic tretch or Hoffmann Reflex Gone Awry? ee Also Calendar of Events Physician Jobs Backfiles of Articles Back to 1929 Clinical Challenge: You Make the Diagnosis Corneal Growth in a 7-Year-Old White Man CME Course Healthy Diets and the ubsequent Prevalence of Nuclear Cataract in Women (REPRNTED) ARCH OPHTHALMOL / VOL 128 (NO. 6), JUNE Downloaded From: on 8/22/ American Medical Association. All rights reserved.