Kenneth M.P. Yee

Vitreoschisis in macular diseases

Objectives Vitreoschisis is a possible pathogenic mechanism in macular diseases. Thus, the vitreoretinal interface was evaluated in monkey eyes and patients with various macular diseases in search of vitreoschisis. It is hypothesised that vitreoschisis is present in macular holes (MH) and macular pucker (MP), but not in other maculopathies. Methods Histopathology was studied in 14 monkey eyes and a vitrectomy specimen of a patient with macular pucker. Optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) was performed in 239 eyes: 45 MH, 45 MP, 51 dry age-related macular degeneration (AMD), 53 non-proliferative diabetic retinopathy (NPDR) and 45 controls. Results Immunohistochemistry demonstrated lamellae in the posterior vitreous cortex of 12/14 (86%) monkey eyes. With OCT/SLO, vitreoschisis was detected in 24/45 (53%) MH and 19/45 (42%) MP eyes, but in only 7/53 (13%) NPDR, 3/51 (6%) AMD and 3/45 (7%) control eyes (p<0.001 for all comparisons). Rejoining of the inner and outer walls of the split posterior vitreous cortex was visible in 16/45 (36%) MH eyes and 15/45 (33%) MP eyes. Histopathology of the MP specimen confirmed a split with rejoining in the posterior vitreous cortex. Conclusions Vitreoschisis was detected in half of eyes with MH and MP, but much less frequently in controls, AMD and NPDR patients. These findings suggest that anomalous PVD with vitreoschisis may be pathogenic in MH and MP.

Vitrectomy for floaters: prospective efficacy analyses and retrospective safety profile.

Purpose: Floaters impact vision but the mechanism is unknown. We hypothesize that floaters reduce contrast sensitivity function, which can be normalized by vitrectomy, and that minimally invasive vitrectomy will have lower incidences of retinal tears (reported at 30%) and cataracts (50–76%). Methods: Seventy-six eyes (34 phakic) with floaters were evaluated in 2 separate studies. Floater etiologies were primarily posterior vitreous detachment in 61 of 76 eyes (80%) and myopic vitreopathy in 24 of 76 eyes (32%). Minimally invasive 25G vitrectomy was performed without posterior vitreous detachment induction, leaving anterior vitreous, and using nonhollow probes for cannula extraction. Efficacy was studied prospectively (up to 9 months) in 16 floater cases with Freiburg Acuity Contrast Testing (Weber index [%W] reproducibility = 92.1%) and the National Eye Institute Visual Function Questionnaire. Safety was separately evaluated in 60 other cases followed up on an average of 17.5 months (range, 3–51 months). Results: Floater eyes had 67% contrast sensitivity function attenuation (4.0 ± 2.3 %W; control subjects = 2.4 ± 0.9 %W, P < 0.013). After vitrectomy, contrast sensitivity function normalized in each case at 1 week (2.0 ± 1.4 %W, P < 0.01) and remained normal at 1 month (2.0 ± 1.0 %W, P < 0.003) and 3 months to 9 months (2.2 ± 1.5 %W, P < 0.018). Visual Function Questionnaire was 28.3% lower in floater patients (73.2 ± 15.6, N = 16) than in age-matched control subjects (93.9 ± 8.0, N = 12, P < 0.001), and postoperatively improved by 29.2% (P < 0.001). In the safety study of 60 floater cases treated with vitrectomy, none developed retinal breaks, infection, or glaucoma after a mean follow-up of 17.5 months. Only 8 of 34 cases (23.5%) required cataract surgery (none younger than 53 years) at an average of 15 months postvitrectomy. Conclusion: Floaters lower contrast sensitivity function, which normalizes after vitrectomy. Visual Function Questionnaire quantified improvement in satisfaction. Not inducing posterior vitreous detachment reduced retinal tear incidence from 30% to 0% (P < 0.007). Postvitrectomy cataract incidence was reduced from 50% to 23.5% (P < 0.02). This approach thus seems effective and safe in alleviating the visual dysfunction induced by floaters.

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.

Proteomic Analysis of Embryonic and Young Human Vitreous.

PURPOSE The proteomic profile of vitreous from second-trimester human embryos and young adults was characterized using mass spectrometry and analyzed for changes in protein levels that may relate to structural changes occurring during this time. This vitreous proteome was compared to previous reports to confirm proteins already identified and reveal novel ones. METHODS Vitreous from 17 human embryos aged 14 to 20 weeks gestation (WG) and from a 12-, a 14-, a 15-, and a 28-year-old was individually analyzed using tandem mass spectrometry-based proteomics. Peptide spectral count associations with embryonic age were assessed using a general linear model of fold changes and Spearmans rank correlation. Differences between embryonic and young adult vitreous proteomes were also compared. Immunohistochemistry was used to evaluate three proteins in five additional fetal (10-18 WG) human eyes. RESULTS There were 1217 proteins identified in fetal and young adult human vitreous, 206 after quantile normalization and variance filtering. In embryos, the peptide counts of 37 proteins changed significantly from 14 to 20 WG: 75.7% increased, 24.3% decreased. Immunohistochemistry confirmed the absence of clusterin and cadherin in 10 and 14 WG eyes and their presence at 18 WG. Comparing embryonic to young adult vitreous, 47 proteins were significantly higher or lower. A total of 768 proteins not previously identified in the literature are presented. CONCLUSIONS Proteins previously unreported in the human vitreous were identified. The human vitreous proteome undergoes significant changes during embryogenesis and young adulthood. A number of protein levels change considerably during the second trimester, with the majority decreasing.

Long-term results of office-based pneumatic retinopexy using pure air

Aims The long-term results of office-based pneumatic retinopexy (PR) using only filtered air were evaluated in a case series of rhegmatogenous retinal detachments with more than 3 years of follow-up, on average. Methods 77 cases of primary rhegmatogenous retinal detachments arising from superior tears (mean=1.6 tears) were treated with cryopexy (n=61) or laser (next day, n=16) and intravitreal injection of pure air in an office setting. The macula was detached preoperatively in 37 eyes (48.1%). Outcome measures were single-operation success, final reattachment rates and visual acuity (VA). Results Subjects were followed for 6–186 months (mean follow-up = 40.7 months, 46.8% ≥2 years, 25% ≥5 years). In all cases, the air bubble was gone within 5 days. Single-operation success was achieved in 62/77 (80.5%) eyes. Repeat PR was successful in four cases, increasing the PR reattachment rate to 85.7%. Scleral buckle was performed on the remaining 11 eyes (14.3%), 1 with vitrectomy. The final reattachment rate was 100%. VA improved ≥2 Snellen lines in 53.2% of patients, with 50/77 (64.9%) attaining VA ≥20/40. Following PR, 87% of subjects had the same or better VA. Conclusions Office-based pure-air PR achieves acceptable reattachment rates with good visual outcomes and long-term efficacy. Eliminating the need for expansile gases makes this approach more widely available, decreases recovery time and lowers healthcare costs.

Inner Retinal Optic Neuropathy: Vitreomacular Surgery- Associated Disruption of the Inner Retina

PURPOSE Macular pucker (MP) and macular hole (MH) are vitreomaculopathies treated by vitrectomy and membrane peel. The complication of postoperative central scotoma can be associated with significant reduction in visual acuity (VA). We seek to determine whether retinal nerve fiber layer (RNFL) disruption is the pathophysiologic basis of this defect. Mitigating clinical circumstances also were sought. METHODS Eleven eyes from 10 pseudophakic patients who had undergone vitrectomy with peeling for either MH or MP were studied with clinical measures, including optical coherence tomography (OCT). Membrane specimens were evaluated by immunohistochemistry for neurofilament, a marker for the inner retina. Ten eyes from 10 pseudophakic patients who underwent repeat surgery for persistent or recurrent pathology were evaluated to determine the relationship between the timing of reoperation and clinical outcome. RESULTS Cases with a postoperative central scotoma (N=4) had worse VA (~20/600) compared to those without (N=7, ~20/30, P=0.01). Eyes with a central scotoma had significantly reduced RNFL thickness in the temporal quadrant (53.67 vs. 72.33 μm, P=0.05) by OCT. A central scotoma was associated with more disruption of the inner retina on immunohistochemistry (P=0.03). In patients with persistent or recurrent pathology, waiting six months before reoperation resulted in better functional outcomes (P=0.03). CONCLUSIONS Central scotomata and poor VA were associated with disruption of the RNFL during membrane peeling. Affected patients have RNFL thinning and signs of optic neuropathy, for which we propose the term inner retinal optic neuropathy (IRON). In patients requiring reoperation, waiting six months between surgeries may reduce the risk of IRON.

Vitreous floaters (Conference Presentation)

BACKGROUND: Vitreous opacities and posterior vitreous detachment (PVD) disturb vision by degrading contrast sensitivity (AJO 172:7-12, 2016). Increased light scattering is the presumed mechanism. To test this hypothesis, dynamic light scattering (DLS) was performed on excised vitreous of patients with clinically significant floaters, and compared to macular pucker controls. METHODS: Undiluted, unfixed vitreous was procured during 25-gauge vitrectomy in 14 subjects (age = 59 ± 6.6 years) with clinically significant vitreous floaters, and 6 controls (age = 66.5 ± 8.7 years; P = 0.10) with macular pucker. Total protein concentration was determined by fluorescent Quant-iTTM protein assay kit (Invitrogen/Molecular Probes, Eugene, OR) with bovine serum albumin (0500 ng/ml) as a standard. Fluorescence (excitation at 470 nm and emission at 570 nm) was measured using a Gemini XPS Dual-Scanning Microplate Spectrofluorometer and data analyzed using SoftMax Pro software (Molecular Devices, Sunnyvale, CA). DLS (NS300, Malvern Instruments, Westborough, MA) measurements were performed in each specimen after 10-fold dilution in phosphate buffered saline to optimize concentration in each specimen and determine the mean number of particles, the particle size distributions, and the average particle sizes. RESULTS: Total protein concentration in vitreous specimens trended higher in macular pucker controls (1037 ± 1038 μg/mL) than eyes with vitreous floaters (353.7 ± 141.1 μg/mL; P = 0.08). When normalized to total protein concentration, the number of particles in vitreous from floater eyes was more than 2-fold greater than controls (P < 0.04). Particle size distributions were similarly two-fold greater in vitreous from floater subjects as compared to controls (P < 0.05). The average particle size in vitreous from floater eyes was 315.8 ± 194.6 nm, compared to 147.7 ± 129.3 nm in macular pucker controls (P = 0.039). CONCLUSIONS: Vitreous from eyes with clinically significant floaters contains more particles of larger sizes as compared to controls, likely accounting for the degradation of contrast sensitivity previously found in these patients (Retina 34:1062-8, 2014; IOVS 56:1611–7, 2015; AJO 172:7-12, 2016). DLS could elucidate the underlying molecular abnormalities in patients afflicted with bothersome vitreous floaters and help develop clinical tools to better measure vitreous floaters as well as test the efficacy of various therapies.

Reply: To PMID 24296397.

To the Editor: We read the article by Sebag et al titled “Vitrectomy for floaters: prospective efficacy analyses and retrospective safety profile” with great interest. In this study, they have found that small-gauge vitrectomy without posterior vitreous detachment (PVD) induction leads to improvement of contrast sensitivity and visual function in eyes with bothersome floaters. They have included patients in whom bothersome floaters persisted on an “average” of 24 months. We are eager to know the range of this average duration so that we understand how sooner or later the surgery was performed. Information about whether the enrolment of patients was consecutive or randomized will also clarify the inclusion process. In efficacy study, they have mentioned that 15 of 16 eyes were phakic. Whether the remaining one eye was pseudophakic or aphakic has not been noted. We are eager to know the cut rate and vacuum used for three-port vitrectomy, which are not mentioned in the article, so that this study could be translated into practice by readers. Authors have noted that they did not do vitrectomy 3 mm to 4 mm behind the lens. We would like to know how they calculated this distance or if it was roughly based on surgeon’s judgment. In safety study, the PVD was absent in 19 eyes before surgery. Of these, one eye developed PVD postoperatively leading to the return of bothersome floaters and requiring repeat vitrectomy. Similarly, 6 of 16 eyes in efficacy study did not have PVD at presentation. However, whether any of these eyes developed PVD postoperatively or not is not mentioned in the article. Additionally, if any of these eyes developed PVD, then would that lead to the return of bothersome floaters is something that could be mentioned in the article.

Vitreous Cytokines and Regression of the Fetal Hyaloid Vasculature

The fetal hyaloid vasculature plays a critical role in many aspects of proper ocular development. The hyaloid artery (HA) is a large vessel that extends from the optic disc through the vitreous where it branches and extends to the posterior surface of the lens to anastamose with the tunica vasculosa lentis (TVL) which supplies nutrients to the developing lens in the fetus (Figure I.D-1). In humans, the entire embryonic vascular system regresses by birth, which is necessary for media clarity and normal vision. Regression of the hyaloid vasculature is a very complex process likely requiring the participation of many proteins. The mechanisms of hyaloid vessel regression are not known, but insight could be obtained by understanding how this fetal vasculature forms. One study of human embryonic vitreous revealed the presence of blood islands composed of aggregates of primitive erythroblasts and hemangioblasts, as early as the seventh week of gestation (WG) [1]. These cell aggregates express hematopoietic stem cell markers, and the ligands for these markers are expressed in high concentrations in the lens and retina, probably functioning to guide the cells into the vitreous body assembling the fetal vitreous vasculature by hemo-vasculogenesis [2].

Macular Hole and Macular Pucker Surgery with Special Emphasis on Reoperations

Recent advances in the techniques of vitrectomy with membrane peeling [See chapter V.A.2. Vitreo-maculopathy surgery], at times with chromodissection [See chapter V.A.3. Chromodissection in vitreo-retinal surgery], have greatly improved patient outcomes. There are, however, risks associated with these procedures, and on rare occasions there can be much worse vision following surgery than preoperatively. This chapter will review the current concepts of pathogenesis and surgical management of macular holes and macular pucker. Special emphasis will be placed on failed cases and reoperations.