Degradation of Contrast Sensitivity Function Following Posterior Vitreous Detachment

GIANCARLO A. GARCIA, MATIN KHOSHNEVIS, KENNETH M.P. YEE, JEANNIE NGUYEN-CUU, JUSTIN H. NGUYEN, AND J. SEBAG

PURPOSE: To evaluate the effect of posterior vitreous symptoms. (Am J Ophthalmol 2016;172:7–12. Ó detachment (PVD) on contrast sensitivity function 2016 Elsevier Inc. All rights reserved.) (CSF) in previously normal eyes, with the hypothesis that PVD reduces CSF. DESIGN: Prospective observational case series. OSTERIOR VITREOUS DETACHMENT (PVD) IS SEPARA- METHODS: At a single clinical practice 28 eyes were tion of the posterior vitreous cortex from the inner evaluated: 8 eyes of 8 adults (mean age 54.4 ± 10.1 years; P limiting membrane of the retina that results from range 39–68 years) with normal CSF documented by age-related liquefaction of the vitreous gel concurrent 1 Freiburg Acuity Contrast Testing (Weber index: %W) with weakening of vitreoretinal adhesion. It was previ- who subsequently experienced PVD, as confirmed by ously postulated that PVD occurs acutely, beginning poste- ultrasonography and optical coherence tomography; 8 riorly and progressing peripherally with entry of liquefied fellow eyes without PVD; and 12 control eyes: 9 eyes vitreous into the retrocortical (preretinal) space, leading with PVD in patients who chose observation and 3 fellow to separation of the posterior vitreous cortex from the 2–5 eyes without PVD. retina. It has recently been proposed, however, that RESULTS: At study entry there was no significant differ- age-related PVD begins insidiously as a localized separation ence in CSF of fellow eye controls (mean 1.44 ± 0.27 % of the posterior vitreous cortex from the perifoveal retina, W; range 1.06–2.00 %W) and eyes that subsequently progressing slowly over months or years until its comple- 6 developed PVD (1.81 ± 0.61 %W; P [ .146; range tion at the time of vitreopapillary separation. The effects 1.01–2.69 %W). Following PVD there was a 52.5% of age-related PVD are usually benign, as most patients reduction in CSF (2.76 ± 0.30 %W; P [ .001; range are asymptomatic and PVD often goes clinically unde- 2.25–3.14 %W). CSF in the patients who chose limited tected until separation from the optic disc produces symp- vitrectomy (2.51 ± 0.46 %W; range 2.03–3.06 %W) toms related to entopic phenomena from the posterior was 41.8% worse than in the eyes with PVD of patients vitreous cortex and/or a Weiss ring. Although many who chose observation (1.46 ± 0.21 %W; P [ .001; patients adapt, some patients are very bothered by PVD- range 1.08–1.87 %W). After vitrectomy, CSF improved induced floaters, even in the absence of hemorrhage and 7–9 by an average of 43.2%, normalizing in each case at inflammation. 9,10 1 month (CSF 1.51 ± 0.28 %W; P [ .001; range Although previous studies have shown that contrast 1.14–2.00 %W), 3 months (1.38 ± 0.10 %W; P [ sensitivity function (CSF) is abnormal in patients with .0002; range 1.28–1.51 %W), and 12 months (1.34 ± vitreous floaters, those studies compared floater patients 0.34 %W; P [ .0001; range 1.01–1.89 %W, n [ 5) with non-floater controls. No previous studies have pro- postoperatively, attaining the same CSF as the control spectively documented changes in a group of individuals fellow eyes (1.34 ± 0.20 %W; range 1.06–1.56 %W). who served as their own controls. The following presents CONCLUSION: PVD is associated with significant a prospective study of patients with previously documented reduction in CSF of previously normal eyes. This normal CSF and new-onset PVD that resulted in clinically quantifiable negative impact on visual function can significant bothersome floaters. As a secondary outcome distinguish patients who are not significantly bothered measure, CSF was assessed postoperatively in a subgroup by vitreous floaters from those with clinically significant of these eyes that underwent limited vitrectomy; however, surgery for vitreous opacities is not the subject of this research endeavor.

Supplemental Material available at AJO.com. Accepted for publication Sep 4, 2016. From the VMR Institute for Vitreous Macula Retina, Huntington Beach, California (G.A.G., M.K., K.M.P.Y., J.N.-C., J.H.N., J.S.); and METHODS University of California, Irvine, School of Medicine, Irvine, California (G.A.G., M.K.). STUDY DESIGN: This prospective, controlled study was Inquiries to J. Sebag, VMR Institute for Vitreous Macula Retina, 7677 Center Ave, Suite 400, Huntington Beach, CA 92647; e-mail: jsebag@ performed in a single clinical practice setting. Institutional VMRinstitute.com review board approval was obtained (St Joseph Health

0002-9394/$36.00 © 2016 ELSEVIER INC.ALL RIGHTS RESERVED. 7 http://dx.doi.org/10.1016/j.ajo.2016.09.005 Accountability Act. Informed consent was obtained from all subjects prior to their participation. The main outcome measure was contrast sensitivity (CSF).

SUBJECTS: Inclusion criteria were the absence of PVD, the presence of normal CSF at study entry, and the subse- quent development of PVD in only 1 eye, allowing the fellow eyes to serve as controls. During the period 2013– 2015, there were 8 consecutive patients (mean age 54.4 6 10.1 years; range 39–68 years) who met these criteria, with no history of eye disease except for myopia in 7 cases (range 1.75 to 6.75 diopters; status post laser-assisted in situ keratomileusis in 2 cases) and bilateral pseudophakia (monofocal intraocular lens) in 1 case. An average of 13.4 6 7.9 (range 8–17) months later, each patient presented with the sudden onset of unilateral floaters and was found to have PVD documented by B-scan ultrasonography (AVISO; Quantel Medical, Clermont- Ferrand, France; Figure 1) and/or combined spectral- domain optical coherence tomography–confocal scanning laser ophthalmoscopy imaging (OCT-SLO; Optos, Marl- borough, Massachusetts, USA; axial resolution of <6 mm and transverse resolution of 20 mm; Figure 2). Fellow eyes had no evidence of PVD, and served as controls. Six of these subjects chose to undergo surgery (see below) and as a further comparison, the CSF measured in the 6 eyes with PVD of these 6 individuals was compared with 9 eyes with PVD in 6 patients who elected observation without surgery, since these individuals did not perceive their floaters as sufficiently bothersome. Among these 6 FIGURE 1. Ultrasonography of posterior vitreous detachment. control subjects, 3 did not have PVD in the fellow eye, (Top) B-scan ultrasound of the left eye in a 54-year-old man whereas 3 did have PVD in the fellow eye. For the 3 sub- before posterior vitreous detachment (Case 3, Table). Prior to jects with bilateral PVD, the average CSF of both eyes posterior vitreous detachment, visual acuity [ 0.80 and was calculated for statistical comparison with the eyes [ contrast sensitivity function 1.69 %W in this eye. (Bottom) that underwent vitrectomy. Ultrasound of the same eye 1 year later when the patient presented with the sudden onset of floaters. Posterior vitreous detachment is evident by the appearance of the posterior vitre- VISION TESTING: The impact of PVD on vision was ous cortex (white arrow). After posterior vitreous detachment, assessed objectively using best-corrected visual acuity (VA; visual acuity remained 0.80 in this eye, but contrast sensitivity Snellen, expressed in decimal notation) and CSF testing 11–14 function declined by 46.7% from 1.69 %W to 2.48 %W. A with the Freiburg Acuity Contrast Test (FrACT). limited vitrectomy was subsequently performed in this eye for FrACT operates on standard backlit light-emitting diode persistently bothersome floaters. At 3 months after surgery, (LED) computer display monitors with luminance calibra- contrast sensitivity function improved by 47.2% from a preop- tion performed prior to each evaluation. Testing was erative level of 2.48 %W to 1.31 %W, which was actually supe- performed at 2.9 meters from the subject’s eye, level to the rior to the contrast sensitivity function of 1.69 %W prior to LED monitor, employing 24 testing trials at a spatial fre- posterior vitreous detachment. At 1 year postoperatively, quency of 5 cycles per degree, using a tumble Landolt C contrast sensitivity function remained improved (1.89 %W) (sized to 20/200) in 8 different orientations. All subjects compared to the preoperative value. Visual acuity remained 0.80 throughout. wore correction if ametropic and were dark adapted for at least 3 minutes before testing. The Weber index, defined as

%W ¼½ðLuminancemax LuminanceminÞ=Luminancemax Human Research Protection Program) and approved for is automatically calculated by the program. A higher the prospective study of quality-of-life changes and visual Weber index (%W) reflects lower CSF. FrACT has previ- function changes before and after vitrectomy for vitreous ously been shown to be a reliable and accurate measure of opacities. The study adhered to the principles of the Decla- CSF in various clinical settings, including PVD.9–14 ration of Helsinki and the Health Insurance Portability and Reproducibility of the FrACT test in our institute was

8 AMERICAN JOURNAL OF OPHTHALMOLOGY DECEMBER 2016 FIGURE 2. Optical coherence tomography of posterior vitreous detachment. Spectral-domain optical coherence tomography– confocal scanning laser ophthalmoscopy (OCT-SLO) image of the right eye of a 41-year-old myopic man (Case 4, Table) with a chronic history of bothersome floaters in the right eye. On study entry, visual acuity was 20/30 (0.67) and contrast sensitivity func- tion was 1.03 %W. Fourteen months later the patient reported a sudden increase in floaters. Visual acuity was still 20/30 (0.67), but contrast sensitivity function diminished by 147% to 2.54 %W. (Top) OCT demonstrated posterior vitreous detachment (posterior vitreous cortex is indicated by the white arrows). (Bottom) SLO demonstrated the vitreous opacities (black arrows). Following limited vitrectomy, contrast sensitivity function improved to 1.42% W at 1 month postoperatively. This improvement persisted at 3 months (1.38 %W) and 12 months (1.41 %W) with a final contrast sensitivity function improvement of 45%.

previously found to be 92.1%10 and in the present study was vs post-PVD and baseline vs post-vitrectomy was determined to be 93.8% (coefficient of variance ¼ 0.062). performed with paired samples t tests. P values less than .05 were considered statistically significant. SURGERY: All patients were advised to attempt coping with the symptoms before considering treatment. After an average of 6.4 6 2.1 months, 6 patients were unable RESULTS to cope and underwent sutureless 25 G vitrectomy, as pre- 10 viously described. AT STUDY ENTRY, ALL 28 EYES HAD NORMAL CSF (MEAN 1.47 6 0.53 %W, range 1.01–2.69 %W), as compared to previous 9–14 STATISTICAL ANALYSES: Statistical analysis was studies. Upon initial evaluation, there were no performed using Statistical Package for Social Sciences statistically significant differences in CSF between control (SPSS) 22.0 (IBM, Chicago, Illinois, USA). Independent eyes (CSF 1.44 6 0.27 %W; range 1.06–2.00 %W) and samples t tests were used to compare mean baseline param- the eyes that subsequently developed symptomatic PVD eters (VA, CSF) between control eyes and eyes with subse- (CSF 1.81 6 0.61 %W, range 1.01–2.69 %W; P ¼ .146; quent PVD. Difference in mean post-PVD CSF between Table). Further, baseline VA (Snellen decimal) was not sta- the patients electing to have surgery and the nonsurgical tistically significantly different (P ¼ .708) between control subgroup was evaluated with an independent samples t eyes (VA 0.88 6 0.13) and subsequently affected eyes test. Comparison of mean CSF between eyes at baseline (VA 0.86 6 0.13).

VOL. 172 POSTERIOR VITREOUS DETACHMENT AND CONTRAST SENSITIVITY 9 TABLE. Prospective Case Series of Posterior Vitreous Detachment Reducing Contrast Sensitivity Function

Baseline CSF (%W) Postvitrectomy CSF (%W)

Case Sex Age (y) Control Eye (Fellow) Subsequently Affected Eye CSF Post-PVD (%W) 3 Months 12 Months

1 Male 53 1.26 1.91 2.65a 1.49 1.01 2 Female 68 1.56 2.56 3.14a 1.28 1.22 3 Male 54 1.32 1.69 2.36a 1.31 1.89 4 Male 41 1.06 1.03 2.39a 1.38 1.41 5 Male 62 1.50 2.69 2.62a 1.51 1.19 6 Male 39 1.42 1.01 2.25 1.32 – 7 Female 61 2.00 1.68 3.10 – – 8 Male 57 1.40 1.87 2.98 – – Mean 6 SD 54.4 6 10.1 1.44 6 0.27 1.81 6 0.61 2.69 6 0.35 1.38 6 0.10 1.34 6 0.34 P ¼ .146 P ¼ .001 P ¼ .0002b P ¼ .0001b %W ¼ %Weber; CSF ¼ contrast sensitivity function; PVD ¼ posterior vitreous detachment. CSF declined (higher %W; see Methods) after PVD in all cases (gray highlight), on average by 52.5% (P ¼ .001). aAverage CSF on 2 visits after PVD and prior to vitrectomy. bComparison of CSF in surgical subgroup at baseline and post-vitrectomy.

from 1.81 6 0.61 %W (range 1.01–2.69 %W) to 2.76 6 0.30 %W (range 2.25–3.14 %W) (P ¼ .001; Table, Figure 3). Mean VA did not significantly change in eyes before (0.86 6 0.13) and after (0.83 6 0.11) PVD (P ¼ .685). After trying to cope for an average of 6.4 6 2.1 (range 4– 10) months following PVD, 6 of these patients complained of persistently bothersome floaters. Vision testing estab- lished that VA at this time (mean 0.87 6 0.10) did not significantly differ from VA of these eyes before PVD (mean 0.88 6 0.14; P ¼ .798). There was, however, persis- tent diminution of CSF in the affected eye (mean 2.51 6 0.46 %W; range 2.03–3.06 %W), which was not signifi- cantly different from the CSF measured in these eyes at the time of initial diagnosis of PVD (P ¼ .781) and was still FIGURE 3. Contrast sensitivity. The leftmost 2 bars indicate significantly worse than CSF in the unaffected eyes at this that at study entry (prior to posterior vitreous detachment 6 [PVD]) there was no statistically significant difference between follow-up time point (mean 1.33 0.24 %W, range 1.04– ¼ the eyes that would ultimately develop PVD and fellow-eye con- 1.89 %W; P .001) and in comparison to mean baseline trols. The third bar from the left indicates that following PVD, CSF of these eyes before PVD (mean 1.98 6 0.68 %W, contrast sensitivity function decreased by 52.5% (P [ .001). range 1.01–2.56 %W; P ¼ .027). The 3 rightmost bars indicate that after limited vitrectomy, As an additional comparison, the CSF in these 6 eyes contrast sensitivity function returned to normal at 1 month was compared with 9 eyes in 6 control patients who had (P [ .001), 3 months (P [ .0002), and 12 months (P [ PVD and floaters that were deemed by these patients to .0001) postoperatively (Error bars represent standard devia- be insufficiently bothersome to warrant surgery. The 3 con- tion.). trol patients with unilateral PVD had a mean CSF of 1.40 6 0.41 %W (range 1.09–1.87 %W) in the eye with PVD, which was not significantly different from mean CSF in For each subject, ultrasound determined that there was no their fellow eyes (1.24 6 0.20 %W, range 1.05–1.52 % PVD in either eye at study entry. However, an average of 13.4 W; P ¼ .377). Among the 3 nonsurgical control patients 6 7.9 (range 8–17) months after study entry, 8 patients with bilateral PVD, average CSF in these 6 eyes was 1.51 presented with the sudden onset of unilateral floaters. In 6 0.24 %W (range 1.13–1.99 %W). Mean CSF of all con- each case, ultrasound documented that PVD had developed trol eyes with PVD in the 6 patients who chose not to un- in the eye with floaters (Figure 1). When the detached poste- dergo surgery was 1.46 6 0.21 %W (range 1.08–1.87 %W), rior vitreous cortex was near the retina, OCT imaging which was 41.8% better than the post-PVD CSF of patients confirmed the presence of PVD (Figure 2). Following PVD, who did elect to have limited vitrectomy (2.51 6 0.46 % CSF declined in the affected eyes by an average of 52.5%, W, range 2.23–3.03 %W; P ¼ .001).

10 AMERICAN JOURNAL OF OPHTHALMOLOGY DECEMBER 2016 The 6 patients who complained of persistently bother- To our knowledge there have been no prospective studies some floaters and had significant reduction in CSF under- using patients as their own controls. Furthermore, the ef- went limited vitrectomy, as previously described.10,14 fects of PVD on CSF were not specifically evaluated in Postoperatively, there were no cases of endophthalmitis, any previous studies. Both matters were addressed in hemorrhage, retinal tears/detachments, glaucoma, the present study, because CSF measurements were ob- hypotony, or macular edema. There was no evidence of tained before and after documented PVD. Furthermore, clinically significant cataract formation and no patients cases were selected to have fellow-eye controls without underwent cataract surgery during the 1-year follow-up PVD by ultrasound and spectral-domain OCT evalua- period. After limited vitrectomy all 6 eyes demonstrated tions. improved CSF (Figure 3). At 1 month postoperatively, At study entry, there was no appreciable difference in mean CSF improved by 43.2%, from 2.66 6 0.30 %W to CSF between the 2 eyes of the patients in this study. After 1.51 6 0.28 %W (range 1.14–2.00 %W; P ¼ .001), which PVD, a significant reduction in CSF was found in each of did not significantly differ from the mean CSF of these 6 the 8 affected eyes. Further, there was worse CSF in pa- eyes before PVD (1.82 %W 6 0.72; P ¼ .350). Similarly, tients with PVD who elected to have surgery as compared at 3 months postoperatively, mean CSF was improved by to those who chose observation without surgery. This sug- 48.1%, from preoperative levels to 1.38 6 0.10 %W (range gests that diminished CSF was associated with desire for 1.28–1.51 %W; P ¼ .0002). At 12 months postoperatively, surgery, and was perhaps a motivation. Moreover, the CSF of the affected eyes improved by an average of 49.6% normalization of CSF following limited vitrectomy is in from baseline to 1.34 6 0.34 %W (range 1.01–1.89 %W; agreement with previous reports10,14 and further supports P ¼ .0001, n ¼ 5), which was nearly identical to that of the postulate that vitreous, specifically PVD, degraded the control eyes (1.34 6 0.20 %W; range 1.06–1.56 %W) CSF in these patients. It is notable that at 1 year post- and did not significantly differ from mean CSF before vitrectomy, CSF levels were the same in the affected eyes PVD (1.98 6 0.68 %W, range 1.01–2.56 %W; P ¼ .184). that had undergone surgery as in the normal fellow eyes In the operated eyes, mean postoperative VA did not signif- without PVD (Table). icantly change at 1 month (0.88 6 0.14; P ¼ .363), 3 months The present study’s main limitation is its small sample (0.81 6 0.12; P ¼ .374), or 12 months (0.82 6 0.11; size. Another consideration is that although the finding P ¼ .463) compared to preoperative VA (0.85 6 0.13). of decreased CSF after PVD in each of these 8 cases is high- ly suggestive, this is an association that does not prove cau- sality. The fact that CSF normalized in each of the 6 cases DISCUSSION that underwent vitrectomy is also very highly suggestive, but still does not prove causation. However, in view of IN MOST INDIVIDUALS, PVD OCCURS WITHOUT PATHO- the statistical significance of the findings in the present logic sequelae15–18 and is only mildly symptomatic. study, this publication is important as a call for larger pro- However, in some patients there can be bothersome spective studies to confirm that CSF is a useful measure of floaters that negatively impact quality of life.7,8,14 Vision, the effect of PVD on vision in the clinical evaluation of pa- in particular VA,19 stray-light glare,20 and CSF,9,10,14 can tients with floaters. This may be vital, as it appears that the 22–25 be considerably affected. This controlled, prospective use of vitrectomy to treat floaters is on the rise and study found that PVD can be associated with significant quantitative measures of CSF testing offer objective and reduction in CSF. reproducible criteria for case selection, so as to avoid the CSF is an important component of visual function performance of surgery for cases that do not warrant such that can impact vision and lower quality of life in spite treatment. Postoperative CSF assessment can also of normal visual acuity.21 Although previous provide a useful objective outcome measure of the studies9,10,14 found diminished CSF in patients with efficacy of surgery or any future forms of therapy, such as 26,27 floaters, these were compared with age-matched controls. pharmacologic vitreolysis.

FUNDING/SUPPORT: NO FUNDING OR GRANT SUPPORT. FINANCIAL DISCLOSURES: THE FOLLOWING AUTHORS HAVE NO financial disclosures: Matin Khoshnevis, Giancarlo A. Garcia, Kenneth M.P. Yee, Justin H. Nguyen, and J. Sebag. All authors attest that they meet the current ICMJE criteria for authorship.

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