J. Sebag

Ultrasound-Based Quantification of Vitreous Floaters Correlates with Contrast Sensitivity and Quality of Life

PURPOSEnClinical evaluation of floaters lacks quantitative assessment of vitreous structure. This study used quantitative ultrasound (QUS) to measure vitreous opacities. Since floaters reduce contrast sensitivity (CS) and quality of life (Visual Function Questionnaire [VFQ]), it is hypothesized that QUS will correlate with CS and VFQ in patients with floaters.nnnMETHODSnTwenty-two eyes (22 subjects; age = 57 ± 19 years) with floaters were evaluated with Freiburg acuity contrast testing (FrACT; %Weber) and VFQ. Ultrasonography used a customized probe (15-MHz center frequency, 20-mm focal length, 7-mm aperture) with longitudinal and transverse scans taken in primary gaze and a horizontal longitudinal scan through premacular vitreous in temporal gaze. Each scan set had 100 frames of log-compressed envelope data. Within each frame, two regions of interest (ROIs) were analyzed (whole-central and posterior vitreous) to yield three parameters (energy, E; mean amplitude, M; and percentage of vitreous filled by echodensities, P50) averaged over the entire 100-frame dataset. Statistical analyses evaluated E, M, and P50 correlations with CS and VFQ.nnnRESULTSnContrast sensitivity ranged from 1.19%W (normal) to 5.59%W. All QUS parameters in two scan positions within the whole-central ROI correlated with CS (R > 0.67, P < 0.001). P50 in the nasal longitudinal position had R = 0.867 (P < 0.001). Correlations with VFQ ranged from R = 0.52 (P < 0.013) to R = 0.65 (P < 0.001).nnnCONCLUSIONSnQuantitative ultrasound provides quantitative measures of vitreous echodensity that correlate with CS and VFQ, providing objective assessment of vitreous structure underlying the functional disturbances induced by floaters, useful to quantify vitreous disease severity and the response to therapy.

Degradation of Contrast Sensitivity Function Following Posterior Vitreous Detachment

PURPOSEnTo evaluate the effect of posterior vitreous detachment (PVD) on contrast sensitivity function (CSF) in previously normal eyes, with the hypothesis that PVD reduces CSF.nnnDESIGNnProspective observational case series.nnnMETHODSnAt a single clinical practice 28 eyes were evaluated: 8 eyes of 8 adults (mean age 54.4 ± 10.1 years; range 39-68 years) with normal CSF documented by Freiburg Acuity Contrast Testing (Weber index: %W) who subsequently experienced PVD, as confirmed by ultrasonography and optical coherence tomography; 8 fellow eyes without PVD; and 12 control eyes: 9 eyes with PVD in patients who chose observation and 3 fellow eyes without PVD.nnnRESULTSnAt study entry there was no significant difference in CSF of fellow eye controls (mean 1.44 ± 0.27 %W; range 1.06-2.00 %W) and eyes that subsequently developed PVD (1.81 ± 0.61 %W; Pxa0= .146; range 1.01-2.69 %W). Following PVD there was a 52.5% reduction in CSF (2.76 ± 0.30 %W; Pxa0= .001; range 2.25-3.14 %W). CSF in the patients who chose limited vitrectomy (2.51 ± 0.46 %W; range 2.03-3.06 %W) was 41.8% worse than in the eyes with PVD of patients who chose observation (1.46 ± 0.21 %W; Pxa0= .001; range 1.08-1.87 %W). After vitrectomy, CSF improved by an average of 43.2%, normalizing in each case at 1xa0month (CSF 1.51 ± 0.28 %W; Pxa0= .001; range 1.14-2.00 %W), 3xa0months (1.38 ± 0.10 %W; Pxa0= .0002; range 1.28-1.51 %W), and 12xa0months (1.34 ± 0.34 %W; Pxa0= .0001; range 1.01-1.89 %W, nxa0= 5) postoperatively, attaining the same CSF as the control fellow eyes (1.34 ± 0.20 %W; range 1.06-1.56 %W).nnnCONCLUSIONnPVD is associated with significant reduction in CSF of previously normal eyes. This quantifiable negative impact on visual function can distinguishxa0patients who are not significantly bothered by vitreous floaters from those with clinically significant symptoms.

Vitreous Floaters and Vision: Current Concepts and Management Paradigms

Floaters most commonly occur in the middle age due to age-related changes in vitreous structure and light scattering by the posterior vitreous cortex after collapse of the vitreous body during posterior vitreous detachment (PVD). In youth, floaters are most often due to myopic vitreopathy. Vitreous floaters can have a negative impact on visual function and in turn the quality of life. Techniques to characterize floaters clinically include ultrasound imaging, optical coherence tomography, and dynamic light scattering for structural characterization. Functional impact can be assessed by straylight measurements, as well as contrast sensitivity testing. When the severity of floater symptomatology is significant, commonly used therapies include neodymium:yttrium-aluminum-garnet (YAG) laser and limited 25-gauge vitrectomy. While the former is of unproven efficacy, the latter has been shown to be a safe, effective, and definitive cure that improves patients’ quality of life and eradicates symptomatology produced by light scattering and diffraction. It is thus reasonable to offer limited vitrectomy to individuals who have attempted to cope unsuccessfully and in whom functional deficit can be objectively demonstrated by testing contrast sensitivity, an important aspect of vision.

Pharmacologic Vitreolysis with Ocriplasmin: Rationale for Use and Therapeutic Potential in Vitreo-Retinal Disorders

With increased knowledge about the origins and pathophysiology of vitreo-retinal disorders—and, in particular, the central role of anomalous posterior vitreous detachment in vitreo-maculopathies—a paradigm shift from surgery to pharmacotherapy is taking place with the development of pharmacologic vitreolysis. The first approved agent for pharmacologic vitreolysis therapy is ocriplasmin, a truncated form of the nonspecific serine protease plasmin. Twelve studies comprise the current ocriplasmin clinical trial program, demonstrating the efficacy and safety of a single intravitreal injection of ocriplasmin for the treatment of patients with symptomatic vitreo-macular adhesion or vitreo-macular traction, including patients with macular holes. Although post-approval implementation of ocriplamsin in clinical practice has shown success rates of up to 78xa0%, there have been recent case reports of acute, transient visual dysfunction. There are thus new initiatives to further refine clinical indications for case selection and to identify possible untoward effects. Although more studies are warranted, it appears that ocriplasmin offers a good alternative to surgery. The future lies in pharmacologic vitreolysis, and the future of pharmacologic vitreolysis lies in prevention. Thus, long-term studies are needed to define a role for pharmacologic vitreolysis, in particular with ocriplasmin, in the prevention of progressive diabetic retinopathy and age-related macular degeneration.

The diagnosis of health

Abstract The disease-oriented perspective of modern medicine is described and the need for greater emphasis on health is discussed. The expansion of medical practice from its current concentration on sick-care to include preventive and promotive care is dependent upon the recognition of health as a diagnosis. A new approach to the evaluation of medical data from a health-oriented perspective is presented. The technique was tested in a Multiphasic Health Screening (MPHS) environment by attempting to identify those individuals with a high likelihood of health. The results show that 88 to 98% of a healthy population could be identified. The ways in which this approach can improve the function of MPHS are discussed. It will be shown that the diagnosis of health can provide a pivotal point of entry into curative, preventive, and promotive health care programs.

Quantifying Visual Dysfunction and the Response to Surgery in Macular Pucker

PURPOSEnTo measure the effects of macular pucker (MP) on macular structure and quantify function by measuring visual acuity (VA), contrast sensitivity (CS), and distortions. The effects of surgery were quantitatively evaluated using these measures.nnnDESIGNnProspective, comparative case series.nnnPARTICIPANTSnFifty-three patients with unilateral MP and normal fellow eyes: 24 operated MP subjects, 17 unoperated controls, and 12 reproducibility subjects.nnnMETHODSnPosterior vitreous detachment was diagnosed by ultrasound and ellipsoid zone disruption (EZD) was determined by OCT, which also measured macular thickness and volume. Vision was assessed, byxa0measuring VA (logMAR) and CS (Freiburg acuity contrast testing: Weber index, %W). A visual distortions index (%DI) was calculated using 3-dimensional threshold Amsler grid testing. Comparisons to controls were performed before surgery and at 1, 3, 6, and 12 months after vitrectomy/membrane peel without chromodissection.nnnMAIN OUTCOME MEASURESnPosterior vitreous detachment (ultrasound), EZD (OCT), macular thickness and volume (OCT), VA (logMAR), CS (%W), distortions (%DI).nnnRESULTSnPosterior vitreous detachment was present in 90% of MP eyes, but only 50% of fellow eyes (Pxa0< 0.001). All structural and functional indices were worse (28% to 5-fold) in the 24 operated MP eyes than the 17 unoperated MP eyes (P < 0.001). Before surgery, EZD was present in 33% of operated MP eyes but none of the unoperated MP eyes (P < 0.02). The macula was thicker (514±85 μm vs. 257±59 μm; P < 0.001) with greater volume (3.22±0.56 μl vs. 2.14±0.22 μl; P < 0.001) in operated MP eyes than normal fellow eyes. Before surgery, MP eyes had VA = 0.53 logMAR (Snellen equivalent, 20/67) vs. controls = 0.21 (20/32); P < 0.001; CS was 8.61±5.36 %W vs. controls = 3.71±1.47 %W (P < 0.001); and distortions were 7.61±12.6 %DI vs. controls = 0.13±0.61 %DI (P < 0.001). EZD was associated with worse VA (P < 0.01) and CS (P < 0.03) before and after surgery. Each outcome measure improved progressively at 1, 3, 6, and 12 months after surgery, but only %DI and macular volume normalized.nnnCONCLUSIONSnThese quantitative measures characterize the impact of MP on macular structure and function. All indices improved after surgery, but only distortions and macular volume normalized. Contrast sensitivity measurements and quantification of distortions can objectively assess visual dysfunction in MP and may be useful outcome measures of therapy.

The effects of aging vitreous on contrast sensitivity function

PurposeContrast sensitivity function (CSF) declines with age. When unassociated with cataracts, this is hypothesized to be due to macular ganglion cell complex (GCC) thinning. However, other studies found associations with increased vitreous echodensity and posterior vitreous detachment (PVD). We investigate the relationship between CSF, vitreous echodensity, PVD, and GCC thickness as related to age in the same subjects.MethodsAge, CSF (Weber index: %W), vitreous echodensity (quantitative ultrasonography [QUS]), lens status (phakia or pseudophakia), best-corrected visual acuity (BCVA), and GCC thickness (SD-OCT) were evaluated in 57 eyes of 57 subjects with (nu2009=u200932, mean ageu2009=u200962xa0years) and without (nu2009=u200925, mean ageu2009=u200944xa0years) PVD (Pu2009<u20090.001). A multivariate linear regression analysis was performed to assess the effects of independent variables on CSF.ResultsCSF was 51.2% worse in eyes with PVD (2.98u2009±u20090.31 %W) compared to no PVD (1.97u2009±u20090.24 %W; Pu2009<u20090.001). QUS was 55.8% greater in eyes with PVD than those without (Pu2009<u20090.001). Among all subjects, PVD status, vitreous echodensity, and age were the only independent variables demonstrating significant effects on CSF. Lens status, BCVA, and GCC thickness did not demonstrate association with CSF.ConclusionsPVD, vitreous echodensity, and age are determinants of CSF. PVD and increased vitreous echodensity are each associated with diminished CSF, independent of age. Thus, in the absence of GCC thinning and cataracts, vitreous changes may be a cause of decreased CSF with age.

Floaters and reduced contrast sensitivity after successful pharmacologic vitreolysis with ocriplasmin

Purpose To describe the onset of floaters and reduction in contrast sensitivity (CS) following successful pharmacologic vitreolysis with ocriplasmin for the treatment of vitreo-macular traction (VMT) in a patient with previously normal CS. Observations A 65-year-old woman with a past ocular history of normal visual acuity (VA = 20/26) and contrast sensitivity (1.81% Weber) presents with a 4-month history of distortions. VA decreased to 20/40 and Optical Coherence Tomography (OCT) demonstrated VMT. Pharmacologic vitreolysis was performed with intravitreal ocriplasmin. Ten weeks later the patient complained of floaters and was found to have a PVD and complete resolution of VMT. VA was still 20/40, but contrast sensitivity decreased by more than 100% to 3.77%Weber. After 6 months of attempted coping, this did not improve, so limited vitrectomy was performed. Post-operative VA = 20/26 and CS improved by 46% from 3.77%W to 2.03%W (normal). Conclusion and importance: This case highlights a little discussed consequence of PVD induction by successful pharmacologic vitreolysis – the development of clinically significant floaters. The resulting reduction of contrast sensitivity was normalized by limited vitrectomy, strongly suggesting that the detached vitreous was the cause.

Management of Macular Edema in Vitreo-Maculopathies

Anomalous PVD is the fundamental cause of vitreo-maculopathies with vitreo-macular traction and macular pucker, both associated with macular edema.

The effects of vitreous on proliferative diabetic retinopathy and the response to pan retinal photocoagulation

Dear Editor: Vitreous plays an important role in a variety of retinal disorders, often via anomalous posterior vitreous detachment (PVD), which can tear/detach the retina, or cause vitreomaculopathies such as macular pucker (via vitreoschisis) and macular holes [1, 2]. In patients with age-related macular degeneration [3] and diabetic retinopathy [4] an attached vitreous portends a worse prognosis than PVD, probably related to mechanical effects as well as higher intraocular VEGF levels in eyes without PVD [5]. Thus, it is understandable that the risk of proliferative diabetic retinopathy (PDR) is less in eyes with PVD than eyes with an attached posterior vitreous, an observation that is well established in the literature [4, 6–8]. It was previously hypothesized that one way in which pan retinal photocoagulation (PRP) might provide therapeutic benefit is by inducing PVD [4, 8, 9]. Studies have in fact shown that the incidence of PVD is greater in patients who had PRP laser therapy than in those who have not had PRP laser therapy, supporting this hypothesis [9]. A recent study [10] identified that retinal neovascularization located posterior to the inner limiting membrane (ILM) was more likely to respond to PRP therapy than retinal neovascularization that was located anterior to the ILM (19/ 25 vs. 13/22, respectively). While statistically significant (P=0.038), the 17% difference between groups is marginally significant clinically. Furthermore, fluorescein angiography was not available for all subjects, yet this test is needed to rule-out intraretinal microvascular abnormalities (IRMA) that should not be included in this study. What is also not described in this series of patients is the relationship of the posterior vitreous to the retina. It is well known that in ischemic retinopathies, retinal neovascularization proliferates into the posterior vitreous cortex [4, 6] and that persistent attachment of vitreous to the retina promotes retinal neovascularization [4, 5, 8]. Thus, the relationship between the posterior vitreous and retina is important information in patients with PDR, especially given the research objectives of the study in question. Yet, this publication [10] repeatedly refers to vitreous as a Bcavity^ rather than a structure that plays an important role in various retinal disorders, especially at its interface with the retina. To establish the state of the vitreo-retinal interface, both ultrasonography and optical coherence tomography (OCT) are needed to conclusively determine the presence or absence of PVD, for OCT alone cannot detect a detached posterior vitreous cortex that is displaced anterior to the imaging range of OCT, about 5 mm from the retina. Thus, the questions to be answered are: Howmany subjects in this study had angiographic evidence of true retinal neovascularization? How many subjects in this study with retinal neovascularization posterior to the ILM had PVD by both OCT and ultrasound? How many with retinal neovascularization anterior to the ILM had PVD? How many in each subgroup developed PVD following PRP therapy? In view of the aforementioned role(s) of the vitreous body in the pathophysiology of PDR, this study should incorporate information about the state of the vitreo-retinal interface to * J. Sebag jsebag@VMRinstitute.com