Hyalocytes-guardians of the vitreoretinal interface.

Originally discovered in the nineteenth century, hyalocytes are the resident macrophage cell population in the vitreous body. Despite this, a comprehensive understanding of their precise function and immunological significance has only recently emerged. In this article, we summarize recent in-depth investigations deciphering the critical role of hyalocytes in various aspects of vitreous physiology, such as the molecular biology and functions of hyalocytes during development, adult homeostasis, and disease. Hyalocytes are involved in fetal vitreous development, hyaloid vasculature regression, surveillance and metabolism of the vitreoretinal interface, synthesis and breakdown of vitreous components, and maintenance of vitreous transparency. While sharing certain resemblances with other myeloid cell populations such as retinal microglia, hyalocytes possess a distinct molecular signature and exhibit a gene expression profile tailored to the specific needs of their host tissue. In addition to inflammatory eye diseases such as uveitis, hyalocytes play important roles in conditions characterized by anomalous posterior vitreous detachment (PVD) and vitreoschisis. These can be hypercellular tractional vitreo-retinopathies, such as macular pucker, proliferative vitreo-retinopathy (PVR), and proliferative diabetic vitreo-retinopathy (PDVR), as well as paucicellular disorders such as vitreo-macular traction syndrome and macular holes. Notably, hyalocytes assume a significant role in the early pathophysiology of these disorders by promoting cell migration and proliferation, as well as subsequent membrane contraction, and vitreoretinal traction. Thus, early intervention targeting hyalocytes could potentially mitigate disease progression and prevent the development of proliferative vitreoretinal disorders altogether, by eliminating the involvement of vitreous and hyalocytes.

IMAGING RHEGMATOGENOUS RETINAL LESIONS AND PERIPHERAL VITREORETINAL INTERFACE WITH WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: Analyze the peripheral vitreoretinal interface with widefield optical coherence tomography. METHODS: Retrospective chart analysis and widefield optical coherence tomography in 120 consecutive cases of rhegmatogenous pathology. RESULTS: There were 166 lesions in 120 eyes, including 106 horseshoe tears, 22 operculated holes, 30 nonoperculated holes, six giant tears, and two peripheral lamellar defects followed for 6.1 ± 1.2 months. Posterior vitreous detachment was present in all eyes (101/101, 100%) with tears and operculated holes, but only in 5/19 eyes (26.3%) with nonoperculated holes ( P < 0.001). Axial vitreous traction was evident at the anterior edge of horseshoe tears (106/106, 100%), but not the posterior border (18/106, 17%, P < 0.001). Operculated holes located posterior to the vitreous base were free from vitreous traction, displaying a morphology similar to the macular hole. Nonoperculated holes were farther anterior with signs of tangential traction in 23/30 (76.7%) cases. Peripheral vitreoschisis was more often associated with nonoperculated holes (25/30, 83.3%), than horseshoe tears (17/106, 16%; P < 0.001). Horseshoe tears and nonoperculated holes were more often associated with retinal detachment (58/106 [54.7%] and 15/30 [50%], respectively) than operculated holes (5/22, 22.7%), P = 0.023. CONCLUSION: Peripheral vitreoretinal interactions are similar to vitreomaculopathies, with axial and vitreoschisis-related tangential traction playing different roles in different rhegmatogenous pathologies. Peripheral optical coherence tomography improves understanding of pathophysiology and risks of retinal detachment.

RECURRENT FLOATERS AFTER LIMITED VITRECTOMY FOR VISION DEGRADING MYODESOPSIA.

PURPOSE: Limited vitrectomy improves vision degrading myodesopsia, but the incidence of recurrent floaters postoperatively is not known. We studied patients with recurrent central floaters using ultrasonography and contrast sensitivity (CS) testing to characterize this subgroup and identify the clinical profile of patients at risk of recurrent floaters. METHODS: A total of 286 eyes (203 patients, 60.6 ± 12.9 years) undergoing limited vitrectomy for vision degrading myodesopsia were studied retrospectively. Sutureless 25G vitrectomy was performed without intentional surgical posterior vitreous detachment (PVD) induction. CS (Freiburg Acuity Contrast test: Weber index, %W) and vitreous echodensity (quantitative ultrasonography) were assessed prospectively. RESULTS: No eyes (0/179) with preoperative PVD experienced new floaters. Recurrent central floaters occurred in 14/99 eyes (14.1%) without complete preoperative PVD (mean follow-up = 39 months vs. 31 months in 85 eyes without recurrent floaters). Ultrasonography identified new-onset PVD in all 14 (100%) recurrent cases. Young (younger than 52 years; 71.4%), myopic (≥-3D; 85.7%), phakic (100%) men (92.9%) predominated. Reoperation was elected by 11 patients, who had partial PVD preoperatively in 5/11 (45.5%). At study entry, CS was degraded (3.55 ± 1.79 %W) but improved postoperatively by 45.6% (1.93 ± 0.86 %W, P = 0.033), while vitreous echodensity reduced by 86.6% ( P = 0.016). New-onset PVD postoperatively degraded CS anew, by 49.4% (3.28 ± 0.96 %W; P = 0.009) in patients electing reoperation. Repeat vitrectomy normalized CS to 2.00 ± 0.74%W ( P = 0.018). CONCLUSION: Recurrent floaters after limited vitrectomy for vision degrading myodesopsia are caused by new-onset PVD, with younger age, male sex, myopia, and phakic status as risk factors. Inducing surgical PVD at the primary operation should be considered in these select patients to mitigate recurrent floaters.

Assessment of Vitreous Structure and Visual Function after Neodymium:Yttrium-Aluminum-Garnet Laser Vitreolysis.

PURPOSE: Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment is performed on vitreous floaters, but studies of structural and functional effects with objective outcome measures are lacking. This study evaluated Nd:YAG laser effects by comparing participants with vitreous floaters who previously underwent laser treatment with untreated control participants and healthy persons without vitreous floaters using quantitative ultrasonography to evaluate vitreous structure and by measuring visual acuity and contrast sensitivity function to assess vision. DESIGN: Retrospective, comparative study. PARTICIPANTS: One eye was enrolled for each of 132 participants: 35 control participants without vitreous floaters, 59 participants with untreated vitreous floaters, and 38 participants with vitreous floaters previously Nd:YAG-treated. Of these, 25 were dissatisfied and sought vitrectomy; 13 were satisfied with observation. METHODS: The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) to assess participant visual well-being, quantitative ultrasonography (QUS) to measure vitreous echodensity, and best-corrected visual acuity (BCVA) and contrast sensitivity function (CSF) to evaluate vision. MAIN OUTCOME MEASURES: Results of NEI-VFQ-39, QUS, BCVA, and CSF. RESULTS: Compared with control participants without vitreous floaters, participants with untreated vitreous floaters showed worse NEI-VFQ-39 results, 57% greater vitreous echodensity, and significant (130%) CSF degradation (P < 0.001 for each). Compared with untreated eyes with vitreous floaters, Nd:YAG-treated eyes had 23% less vitreous echodensity (P < 0.001), but no differences in NEI-VFQ-39 (P = 0.51), BCVA (P = 0.42), and CSF (P = 0.17) results. Of 38 participants with vitreous floaters who previously were treated with Nd:YAG, 25 were dissatisfied and seeking vitrectomy, whereas 13 were satisfied with observation. Participants seeking vitrectomy showed 24% greater vitreous echodensity (P = 0.018) and 52% worse CSF (P = 0.006). Multivariate linear regression models confirmed these findings. CONCLUSIONS: As a group, participants previously treated with Nd:YAG laser for bothersome vitreous floaters showed less dense vitreous, but similar visual function as untreated control participants with vitreous floaters. Because some treated eyes showed less dense vitreous and better visual function than those of untreated control participants, a prospective randomized study of Nd:YAG laser treatment of vitreous is warranted, using uniform laser treatment parameters and objective quantitative outcome measures.

STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF LAMELLAR MACULAR HOLES.

PURPOSE: Lamellar macular holes (LMHs) can been subdivided into tractional and degenerative subtypes. This cross-sectional cohort study compared structural and functional characteristics in these subtypes hypothesizing that tractional LMH has a higher prevalence of vitreopapillary adhesion and tangential traction (macular pucker), whereas degenerative LMH has more ellipsoid zone disruption and worse vision, measured three different ways. METHODS: Tractional LMH (n = 22) and degenerative LMH (n = 15) were distinguished by optical coherence tomography criteria. Separate spectral domain optical coherence tomography scanning of the macula and optic disk was performed. Visual acuity, contrast sensitivity function (Weber Index, %W), and the degree of visual distortions (3-dimensional threshold Amsler grid; % volume lost [%VL]) were quantified. RESULTS: Vitreopapillary adhesion was present in 14/22 (64%) tractional, but in only 3/15 (20%) degenerative LMH (P = 0.006). Macular pucker was present in 19/22 (86%) tractional, but in only 8/15 (53%) degenerative LMH (P = 0.011). Ellipsoid zone disruption was present in 13/15 (87%) degenerative, but in only 2/22 (9%) tractional LMH (P = 0.0001). Visual acuity was better in tractional than degenerative LMH (P = 0.006), as was contrast sensitivity function (tractional = 3.44 ± 1.07 %W, degenerative = 4.66 ± 1.73 %W; P = 0.015). Visual distortions were less in tractional (0.33 ± 0.61 %VL) than in degenerative (0.85 ± 0.68 %VL) LMH (P = 0.014). CONCLUSION: Structure and visual function differ significantly in subtypes of LMH. Tractional LMH has 3-fold higher prevalence of vitreopapillary adhesion and 2-fold higher prevalence of macular pucker. Degenerative LMH has 9-fold more ellipsoid zone disruption, worse visual acuity and contrast sensitivity function, and 3-fold more distortions. Thus, outer retinal integrity seems more closely correlated with vision than anterior structural abnormalities in LMH.

PARS PLANA VITRECTOMY FOR THE TREATMENT OF TRACTIONAL AND DEGENERATIVE LAMELLAR MACULAR HOLES: Functional and Anatomical Results.

PURPOSE: Functional and anatomical outcomes of vitrectomy with membrane peeling were compared in tractional lamellar macular holes (LMH)/macular pseudoholes (MPH) versus degenerative LMH. METHODS: This multicenter retrospective study enrolled patients with a minimum follow-up of 6 months. The association of spectral domain optical coherence tomography parameters with preoperative and postoperative best-corrected visual acuity was analyzed. RESULTS: Seventy-seven (74.8%) tractional LMH/MPH and 26 (25.2%) degenerative LMH were included. Preoperative best-corrected visual acuity was better in tractional LMH/MPH (0.39 ± 0.2 logarithm of the minimal angle of resolution, 20/50 Snellen equivalent) than degenerative LMH (0.56 ± 0.2 logarithm of the minimal angle of resolution, 20/66 Snellen equivalent; P < 0.001). Premacular membranes were found in all tractional LMH/MPH, whereas LMH-associated epiretinal proliferation (LHEP) was present in all degenerative LMH. Primary anatomical success was achieved in 97/103 eyes (94.2%), with foveal restoration occurring earlier in degenerative LMH (1.6 ± 2.3 vs. 3.3 ± 3.6 months; P = 0.025). Best-corrected visual acuity improved in both tractional LMH/MPH and degenerative LMH (P < 0.001 and P = 0.012, respectively) but was better in tractional LMH/MPH (P = 0.001). CONCLUSION: The presence of premacular membranes and absence of LMH-associated epiretinal proliferation in all tractional LMH/MPH further distinguishes this from degenerative LMH. Best-corrected visual acuity improved in both subgroups but more so in tractional LMH/MPH. Complete anatomical restoration of foveal microanatomy was rare in degenerative LMH, reflecting significant morphological and pathophysiological differences between the two lesions.

The effects of aging vitreous on contrast sensitivity function.

PURPOSE: Contrast 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. METHODS: Age, 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 (n = 32, mean age = 62 years) and without (n = 25, mean age = 44 years) PVD (P < 0.001). A multivariate linear regression analysis was performed to assess the effects of independent variables on CSF. RESULTS: CSF was 51.2% worse in eyes with PVD (2.98 ± 0.31 %W) compared to no PVD (1.97 ± 0.24 %W; P < 0.001). QUS was 55.8% greater in eyes with PVD than those without (P < 0.001). 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. CONCLUSIONS: PVD, 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.

Quantifying Visual Dysfunction and the Response to Surgery in Macular Pucker.

PURPOSE: To 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. DESIGN: Prospective, comparative case series. PARTICIPANTS: Fifty-three patients with unilateral MP and normal fellow eyes: 24 operated MP subjects, 17 unoperated controls, and 12 reproducibility subjects. METHODS: Posterior 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, by measuring 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. MAIN OUTCOME MEASURES: Posterior vitreous detachment (ultrasound), EZD (OCT), macular thickness and volume (OCT), VA (logMAR), CS (%W), distortions (%DI). RESULTS: Posterior vitreous detachment was present in 90% of MP eyes, but only 50% of fellow eyes (P < 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. CONCLUSIONS: These 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.

Light Scattering by Vitreous of Humans With Vision Degrading Myodesopsia From Floaters.

Purpose: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL. Methods: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission in vitro. Results: All indices of vitreous echodensity in vivo correlated positively with straylight at 0.5° (R = 0.708 to 0.775, P = 0.049 and 0.024, respectively). Straylight mean scatter index correlated with echodensity (R = 0.71, P = 0.04) and VQOL (R = -0.82, P = 0.0075). Dark-field measures in vitro correlated with degraded CS in vivo (R = -0.69, P = 0.04). VQOL correlated with straylight mean scatter index (R = -0.823, P = 0.012). Conclusions: Increased vitreous echodensity in vivo is associated with more straylight scattering in vitro, validating ultrasonography as a clinical surrogate for light scattering. Contrast sensitivity in vivo is more degraded in the presence of dark-field scattering in vitro and VQOL is decreased in patients whose vitreous has increased light scattering. These findings could form the basis for the development of optical corrections for VDM or support new laser treatments, as well as novel pharmacotherapy.

Oct-based interpretation of the vitreomacular interface and indications for pharmacologic vitreolysis.

PURPOSE: To review the role of optical coherence tomography (OCT) in diagnosis and management of vitreomacular disease and the impact of OCT on potential uses of ocriplasmin, a new pharmacologic vitreolysis agent recently approved by the U.S. Food and Drug Administration for the treatment of symptomatic vitreomacular adhesion. METHODS: Analysis of current literature regarding OCT in diagnosis and management of vitreomacular interface disease. RESULTS: Posterior vitreous detachment is typically a nonpathologic age-related event. Anomalous posterior vitreous detachment emerges when the vitreous cortex fails to cleanly detach from the macula, optic nerve, or other adherent sites. Focal vitreomacular adhesion is a nonpathologic anatomical designation associated with perifoveal posterior vitreous detachment but normal retinal morphology on OCT. Vitreomacular traction is a pathologic consequence of persistent vitreous attachment with structural disturbance of the macular retina visible on OCT. Full-thickness macular holes are foveal defects continuous through all retinal layers to the retinal pigment epithelium. Vitreomacular traction and macular hole with focal vitreomacular adhesion are indications for pharmacologic vitreolysis. CONCLUSION: Noninvasive high-resolution OCT imaging has transformed the understanding of vitreomacular interface disease. Careful evaluation of the vitreomacular interface with OCT has increased in importance with the introduction of ocriplasmin for vitreomacular adhesion associated with symptomatic anatomical retinal changes.

[Role of vitreous in the pathogenesis of neovascular age-related macular degeneration]. / Die Rolle des Glaskörpers in der Pathogenese der exsudativen altersabhängigen Makuladegeneration.

Age-related changes in vitreous molecular and anatomic morphology begin early in life and involve two major processes: vitreous liquefaction and weakening of vitreo-retinal adhesion. An imbalance in these two processes results in anomalous posterior vitreous detachment (PVD), which comprises, among other conditions, vitreo-macular adhesion (VMA) and traction (VMT). VMA is more common in patients with neovascular age-related macular degeneration (nAMD) than age-matched control patients, with the site of posterior vitreous adherence to the inner retina correlating with location of neovascular complexes. The pernicious effects of an attached posterior vitreous on age-related macular degeneration (AMD) progression involve mechanical forces, enhanced fluid influx and inflammation in and between the retinal layers, hypoxia leading to an accumulation of vascular endothelial growth factor (VEGF) and other stimulatory cytokines, and probably an infiltration of hyalocytes. It has been shown that vitrectomy not only mitigates progression to end-stage AMD, but existing choroidal neovascularization regresses after surgery. Thus, surgical PVD induction during vitrectomy or by pharmacologic vitreolysis may be considered in non-responders to anti-VEGF treatment with concomitant VMA.

[Vitreoretinal surgery in age-related macular degeneration]. / Vitreoretinale Chirurgie bei altersabhängiger Makuladegeneration.

The structure of the vitreous body, its interaction with the retinal surface and tractive alterations of the vitreoretinal interface may play a role in the pathogenesis and the development of age-related macular degeneration (AMD). From clinical trials it can be concluded that posterior vitreous detachment (PVD) or vitreous removal may protect against the development of neovascular AMD. Vitreomacular adhesions may promote neovascular AMD and may have an impact on the efficacy and frequency of intravitreal vascular endothelial growth factor (VEGF) inhibition. Therefore, vitreomacular surgery may be considered as a treatment option in selected cases. Peeling of epimacular membranes and the internal limiting membrane (ILM) may contribute to stabilizing visual acuity and reducing the treatment burden of current intravitreal pharmacotherapy. At present, surgical interventions in AMD are mainly performed in cases of submacular hemorrhage involving the fovea. The treatment is not standardized and consists of liquefaction of the blood using recombinant tissue plasminogen activator (rTPA) and its pneumatic displacement, potentially combined with VEGF inhibition. Other submacular surgical strategies, such as choroidal neovascularization (CNV) extraction, macular translocation or transplantation of retinal pigment epithelium (RPE) are currently limited to selected cases as a salvage treatment; however, the development of these submacular surgical interventions has formed the basis for new approaches in the treatment of dry and neovascular AMD including submacular or intravitreal gene and stem cell therapy.

Machine Independence of Ultrasound-Based Quantification of Vitreous Echodensities.

Purpose: Quantitative ultrasound (QUS) provides objective indices of Vision Degrading Myodesopsia (VDM) that correlate with contrast sensitivity (CS). To date, QUS methods were only tested on a single ultrasound machine. Here, we evaluate whether QUS measurements are machine independent. Methods: In this cross-sectional study, 47 eyes (24 subjects; age = 53.2 ± 14.4 years) were evaluated with Freiburg acuity contrast testing (%Weber), and ultrasonography using 2 machines: one with a 15-MHz single-element transducer and one with a 5-ring, 20-MHz annular-array. Images were acquired from each system in sequential scans. Artifact-free, log-compressed envelope data were processed to yield three parameters (mean amplitude, M; energy, E; and percentage filled by echodensities, P50) and a composite score (C). A B-mode normalization method was applied to the 20-MHz datasets to match QUS parameters at both frequencies. Statistical analyses were performed to evaluate correlations among CS, E, M, P50, and C for both machines. Results: QUS parameters from each machine correlated with CS (R ≥ 0.57, P < 0.001) and there was correlation between machines (R ≥ 0.84, P < 0.001). Correlations between CS and QUS parameters were statistically similar for both machines (P ≥ 0.14) except when the 20-MHz data were normalized (P = 0.04). Reproducibility of QUS parameters computed from 20-MHz data were satisfactory (52.3%-96.3%) with intraclass correlation values exceeding 0.80 (P < 0.001). Conclusions: The high correlation between QUS parameters from both machines combined with a statistically similar correlation to CS suggests QUS is an effective, machine-independent, quantitative measure of vitreous echodensities. Translational Relevance: QUS may be applied across clinical ophthalmic ultrasound scanners and imaging frequencies to effectively evaluate VDM.