The development of vitreous membranes and retinal detachment induced by intravitreal carbon microparticles

We induced intravitreal cellular proliferation by injection of carbon microparticles (size 20–70 nm) into the vitreous of 21 eyes of 11 cynomolgus monkeys. Pathological changes were evaluated by light and electron microscopy. At 1 week, there was conspicuous cyclitis showing exudative separation of the nonpigmented and pigmented ciliary epithelium, inflammatory cells, mononuclear phagocytes, and premacular vitreous detachment. At 3 weeks, continued macrophagic response was accompanied by fibrovascular proliferation with ingrowth of vessels from the ciliary body into the vitreous. At 4–5 weeks, deposition of extracellular fibrous material and traction retinal detachment (RD) were found. At 10 weeks, all eyes had extensive RD with pre- and subretinal collagenous cellular membranes. Carbon-laden macrophages were aggregated over the optic disc and fovea with prepapillary neovascularization and cystoid macular edema. Thus, intravitreal fibrovascular proliferation, vitreous contraction, and RD were induced by inflammatory and phagocytic response to carbon particles.Presented in part before the Association for Research in Vision and Ophthalmology, Sarasota, Florida, 30 April 1986     

Posterior vitreous separation and retinal detachment induced by macrophages

Macrophages, which migrate into the vitreous in conditions such as vitreous hemorrhage and penetrating ocular injury, may contribute to the development of intravitreous cellular proliferation and posterior vitreous separation. To investigate this possibility, activated macrophages were harvested from the peritoneal cavity and injected into the vitreous of rabbits. As early as 8 days after macrophage injection, posterior vitreous separation and glial epiretinal membrane formation began to occur. Two weeks after injection, vitreous strands that approached the optic disc and medullary rays were evident; fibroblasts proliferated over the disc or rays and induced retinal detachment. These findings support the hypothesis that macrophages in the vitreous may, in part, mediate cellular proliferation and posterior vitreous separation.This study was supported in part by grants EY02061 and EY03040 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland, and an award from Research To Prevent Blindness, Inc., New York, New YorkThe animals used in this study were maintained in animal care facilities fully accredited by the American Association of Laboratory Animal Science.     

Vitreoschisis in Eales' disease: pathogenic role and significance in surgery

PURPOSE: To report the surgical anatomy of vitreoretinal adhesions as observed intraoperatively in patients undergoing vitreous surgery for complications of Eales' disease. METHODS: Eighteen consecutive male patients (18 eyes) undergoing vitrectomy for Eales' disease were studied prospectively. Intraoperative diagnosis was vitreous hemorrhage (VH) in nine cases, traction retinal detachment (TRD) in four, VH and TRD in three, and combined traction-rhegmatogenous retinal detachment in two. Epiretinal membranes (ERMs) obtained during surgery were studied using light microscopy and immunohistochemistry. RESULTS: An incomplete posterior vitreous detachment was observed in all eyes. Multifocal vitreoretinal adhesions were evident in 83.3% of eyes. The proliferation was fibrovascular in 10 eyes and fibrous in eight. A radial traction fold extending from optic disk to periphery was observed in three eyes. A double-layered membrane, probably the result of vitreoschisis, caused tangential traction. ERMs consisted principally of type II collagen and the cellular element was predominantly composed of lymphocytes, glial cells, and macrophage-like cells (probably hyalocytes). CONCLUSIONS: Fibrous and fibrovascular proliferations have multiple areas of adhesions to the posterior vitreous cortex. The presence of type II collagen in the ERM indicates a possible vitreous collagen component to the double-layered membranes (vitreoschisis). Recognition of the double-layered membranes aids in relief of traction during surgery by delamination.     

Management of proliferative diabetic retinopathy

Proliferative diabetic retinopathy is characterized by neovascularization originating from the retina and/or optic disk in patients with diabetes mellitus. The role of vascular endothelial growth factor appears to be central in the pathogenesis of proliferative diabetic retinopathy. Advanced glycation end products are important in the development of vitreous abnormalities in proliferative diabetic retinopathy. The majority of the neovascular membranes are adherent to the posterior vitreous cortex. When the posterior hyaloid exerts traction, the edges of the neovascular complex are pulled forward, resulting in vitreous hemorrhage. Tractional and/or rhegmatogenous retinal detachments can occur. The Diabetic Retinopathy Study demonstrated the ability of panretinal photocoagulation to reduce the rate of severe visual loss by 50% for eyes with high-risk characteristics, defined as neovascularization originating from the optic disk > 1/3 disk diameter, any neovascularization originating from the optic disk with hemorrhage, and neovascularization originating from the retina with vitreous hemorrhage. The Early Treatment Diabetic Retinopathy Study showed that patients with type II diabetes mellitus who were older than 40 with severe nonproliferative diabetic retinopathy (defined as hemorrhages in four quadrants, venous beading in two quadrants, or intraretinal microvascular abnormalities in one quadrant) also benefited from early panretinal photocoagulation. The Diabetic Retinopathy Vitrectomy Study showed that early vitrectomy (within 6 months of onset of vitreous hemorrhage) was associated with better results in type I diabetes mellitus patients only. The goals of vitreous surgery are to remove the vitreous, including the posterior hyaloid, and to relieve traction from fibrovascular tissue. Delamination and segmentation techniques have been used in the excision of fibrovascular growth on the internal limiting membrane and extending into the vitreous. Panretinal photocoagulation is an integral component of vitrectomy for proliferative diabetic retinopathy. Anti-vascular endothelial growth factor agents may be used in addition to laser as an adjunct to reduce the risk of neovascularization. Vitrectomy surgery may have intraoperative and postoperative complications, including cataract, anterior hyaloidal fibrovascular proliferation, fibrovascular ingrowth, retinal detachment, and recurrent vitreous hemorrhage. Visual potential depends on the preoperative and postoperative status of the macula, as well as on retinal perfusion and the health of the optic nerve. With the improvement in instruments, techniques, and drugs, the results of vitrectomy in proliferative diabetic retinopathy are improving.     

Intraretinal proliferation induced by retinal detachment

Cellular proliferation after retinal detachment was studied by 3H-thymidine light microscopic autoradiography in cats that had experimental detachments of 0.5-180 days duration. The animals underwent labeling 2 hr before death with an intraocular injection of 200 microCi of 3H-thymidine. The number of labeled nuclei were counted in 1-micron thick tissue sections in regions of detachment, in regions of the experimental eyes that remained attached, and in control eyes that had no detachments. In the normal eye, in one that had only the lens and vitreous removed, and in the eyes with 0.5- and 1-day detachments, the number of labeled nuclei ranged from 0/mm (0.5-day detachment) to 0.38/mm (lens and vitreous removed only). By 2 days postdetachment, the number of labeled nuclei increased to 2.09/mm. The highest levels of labeling occurred in two animals with detachments of 3 (7.86/mm) and 4 (7.09/mm) days. Thereafter, the numbers declined steadily until near-baseline counts were obtained at 14 days. The number of labeled nuclei was slightly elevated in the attached regions of two animals with 3-day detachments. Labeled cell types included: Müller cells, astrocytes, pericytes, and endothelial cells of the retinal vasculature, and both resident (microglial cells) and invading macrophages. In an earlier study RPE cells were also shown to proliferate in response to detachment. Thus, these data show that proliferation is a rapid response to detachment, reaching a maximum within 4 days, and that virtually every nonneuronal cell type in the retina can participate in this response. The data suggest that events leading to such clinical manifestations as proliferative vitreoretinopathy and subretinal fibrosis may have their beginnings in this very early proliferative response.     

严重PDR玻璃体切割术后雷珠单抗注射的效果观察

目的：对严重增殖性糖尿病视网膜病变的患者行玻璃体切割术后行雷珠单抗注射的效果观察。方法：回归性分析。12例严重增殖性糖尿病视网膜病变患者(12眼)接受睫状体平坦部玻璃体切割术,同时给予硅油、惰性气体或者平衡液的玻璃体腔填充。在手术结束的同时给予雷珠单抗的玻璃体腔注射。结果：随访时间平均为2.75 mo。这12眼中分别包括玻璃体积血(1眼);玻璃体积血伴纤维血管化增生(1眼);玻璃体积血伴牵拉性视网膜脱离(3眼);纤维血管化增生伴牵拉性视网膜脱离(2眼);玻璃体积血伴新生血管性青光眼伴牵拉性视网膜脱离(1眼);玻璃体积血伴纤维血管化增生伴牵拉性视网膜脱离(2眼);玻璃体积血伴纤维血管化增生伴新生血管性青光眼伴牵拉性视网膜脱离(1眼);玻璃体积血伴牵拉性孔源性视网膜脱离(1眼)。12眼中,8眼行玻璃体腔硅油填充,2眼行惰性气体填充,2眼行平衡液填充。所有的患者之前均未接受任何治疗。视网膜脱离复位率为10/10(100%)。1眼术后出现前房积血。9眼术后最佳矫正视力较术前提高,2眼无明显变化,1眼较术前下降。 OCT检查显示8眼术后未见黄斑水肿。结论：玻璃体切割术后雷珠单抗注射对严重增殖性糖尿病视网膜病变患者有明显的治疗效果：手术成功率明显提高;患者视力显著提高;糖尿病黄斑水肿的发生概率减少;术中及术后并发症的发生率降低。     

Results of vitrectomy for proliferative diabetic retinopathy

The authors treated 1007 eyes with vitrectomy for complications of proliferative diabetic retinopathy. Indications for surgery were: vitreous hemorrhage, 353 eyes (35%); traction retinal detachment, 360 eyes (36%); combined traction-rhegmatogenous retinal detachment, 172 eyes (17%); and other progressive fibrovascular proliferation 122 eyes (12%). During the study period, the frequency of vitreous hemorrhage as an indication for surgery decreased from 42 to 25%, and other progressive fibrovascular proliferation increased from 5 to 22%. The frequency of traction and traction/rhegmatogenous retinal detachments did not change. The results of surgery varied according to the indication. Seventy-nine percent of eyes with vitreous hemorrhage obtained final vision of 5/200 or better. Similar results were obtained in 64% of eyes with traction detachment, 56% of eyes with rhegmatogenous detachment, and 81% of eyes with progressive fibrovascular proliferation. The percentage of eyes achieving final vision of 20/100 or better are as follows: vitreous hemorrhage, 48%; traction detachment, 27%; rhegmatogenous detachment, 24%; and progressive fibrovascular proliferation, 46%. The success rate improved in each anatomic category during the last 3 years of the study.     

Experimental proliferative vitreoretinopathy in rabbits after intravitreous gas injection and creation of retinal hole: ophthalmic findings and localization of fibronectin]

An animal model of rhegmatogenous retinal detachment and proliferative vitreoretinopathy (PVR) has been developed by the creation of a retinal hole (4 disc diameter) 4 days after the intravitreous injection of 0.4 ml of 100% of perfluoropropane (C3F8) in pigmented rabbits. Ophthalmic and histological examination showed detached retina with associated preretinal, intravitreous membranes containing pigmented fibroblast-like cells. Fibrovascular membranes were noted within the puckered medullary wings. Fluorescein angiography revealed profuse leakage from detached medullary wings. Using immunofluorescence, fibronectin was localized on preretinal, intravitreous, and fibrovascular membranes. These results suggested that the breakdown of the blood-retinal barrier and fibrovascular proliferation in addition of previously recognized cell types may be the important factors in this reliable model of PVR.     

Injured vitreous stimulates DNA synthesis in retinal pigment epithelial cells in culture and within the vitreous

Cultures of rabbit retinal pigment epithelium (RPE) were exposed to normal vitreous and to vitreous injured by intravitreal injection of foreign particles. Counts of labeled RPE nuclei after incubation with³H-thymidine in vitro indicated an increase in DNA synthesis with exposure to normal vitreous and an even greater increase with exposure to injured vitreous. Fractionation of injured vitreous demonstrated that the apparent proliferation stimulus resided in the cell-free supernate. The data suggest that normal vitreous contains a humoral factor that stimulates RPE proliferation and that levels of an active agent increase after vitreal injury. RPE injected into the vitreous also responds by increased DNA synthesis to subsequent vitreal injury. This observation implies that foreign substances in the vitreous, as after vitreal hemorrhage, promote development of extraretinopathies involving RPE by stimulating intravitreal proliferation of invasive RPE cells.     

Phagocytes that invade the vitreous after injury stimulate DNA synthesis in neural retina in vitro

Phagocytes that invade the rabbit vitreous after intravitreal injection were co-cultured with cells from the rabbit neural retina. Counts of labeled nuclei after exposure to ³H-thymidine indicate an increase in DNA synthesis by retinal cells exposed to the phagocytes. In contrast, using the same procedures, vitreal phagocytes do not promote DNA synthesis by rabbit dermal fibroblasts in vitro. The apparent proliferation stimulus due to vitreal phagocytes may be functionally related to other macrophage-dependent proliferation-stimulating activities. Since blood components promote vitreal phagocyte invasion, ocular hemorrhage may aggravate some extraretinopathies in part by a phagocyte-mediated stimulation of retinal cell proliferation.     

Vitreous hemorrhage nontoxic to retina as a stimulator of glial and fibrous proliferation

To test the belief that blood is toxic to the retina, we developed an experimental model of vitreous hemorrhage in rabbits by injecting various amounts of autologous, uncoagulated , whole blood into their vitreous cavities, with the vitreous humor either intact or previously compressed by an expanding perfluoropropane gas bubble. Blood in the eyes with compressed vitreous cleared in half the time required for the same volume injected into eyes with intact vitreous (75.6 days vs 39.2 days). Large volumes of intravitreal blood (0.25 to 0.50 ml) were never toxic to the retina by ganzfeld and bright-flash electroretinography throughout a four-month observation period. The results indicated that massive vitreous hemorrhage has a dense filtering effect that can extinguish the ganzfeld but not the bright-flash electroretinogram. Blood caused moderate hemoglobin staining of the retina, without significant iron staining (confirmed by X-ray microprobe analysis). Hemoglobin residues accumulated within cells of the inner retina, especially Müller's cells. Blood clot retraction after the injection of large volumes of fresh blood (1 ml) produced traction retinal detachment, hole formation, and subretinal accumulation of blood. This correlated with a complete and persistent extinction of the ganzfeld and bright-flash electroretinograms throughout the four-month observation period. A striking finding was that almost all eyes developed glial membranes on the peripheral retina. Fibrous membranes, causing local retinal contraction, were found over the medullary wings and optic disk in eyes with vitreous compression.     

Vitrectomy in the management of diabetic eye disease.

Vitrectomy techniques including endolaser photocoagulation allow visual rehabilitation in many eyes that are otherwise untreatable. Discerning the indications and timing for diabetic vitrectomy is increasingly important as the treatment of complications of diabetic retinopathy continues to undergo modification and redefinition. The most common indications for diabetic vitrectomy include: 1) severe nonclearing vitreous hemorrhage; 2) traction retinal detachment recently involving the macula; 3) combined traction and rhegmatogenous detachment; 4) progressive fibrovascular proliferation; and 5) rubeosis iridis and vitreous hemorrhage for eyes in which the media opacity has prevented adequate laser photocoagulation. Other less common indications in selected cases include dense premacular hemorrhage, ghost cell glaucoma, macular edema with premacular traction, cataract preventing treatment of severe, proliferative diabetic retinopathy, anterior hyaloidal fibrovascular proliferation, and fibrinoid syndrome with retinal detachment. The rationale and surgical objectives are discussed and results are summarized.     

Experimental intravitreal proliferation and neovascularization in the cynomolgus monkey

An experimental model for intravitreal cellular proliferation was produced by injection of carbon micro- particles into the vitreous of nine cynomolgus monkeys. Eighteen eyes were studied following enucleations 10 weeks after the injections. Histological examinations showed retinal folds or detachments in 16 eyes, while 6 of those had total detachments. Eight eyes contained transvitreal fibro- vascular strands, passing from the optic disk to a cyclitic retrolental membrane. The strands and membranes were composed mainly of infiltrates of macrophages, inflammatory cells, fibroblasts, newly formed vessels and van Gieson- staining collagen. Epiretinal proliferation of glial cells also occurred. These experiments indicate that a primarily phagocytic cellular invasion into the vitreous is capable of stimulating further cellular migration and growth and for inducing fibrovascular proliferations.Presented at the 1984 meeting of the Club Jules Gonin in Lausanne, Switzerland     

Different outcome among eyes with proliferative diabetic retinopathy indicated for vitrectomy

PURPOSE: The postoperative outcome was evaluated in each group of surgical indications of vitreous surgery for proliferative diabetic retinopathy (PDR), to investigate the factors responsible for postoperative visual prognosis. METHODS: Primary vitrectomy was performed in 119 eyes of 92 patients with PDR. Average postoperative follow-up period was 19 months. The indications for vitrectomy included vitrous hemorrhage in 58 eyes, macular tractional retinal detachment in 17 eyes, extramacular tractional retinal detachment in 10 eyes, macular heterotopia in 11 eyes, and progressive fibrovascular proliferation in the posterior fundus in 23 eyes. RESULTS: The visual acuity finally improved by 2 lines or more in 91 eyes (77%), remained unchanged in 10 eyes (8 %), and decreased by 2 lines or more in 18 eyes (15%). Final postoperative visual acuity was significantly better in cases of vitreous hemorrhage or progressive fibrovascular proliferation in the posterior fundus than in others. Preoperative rubeosis iridis and macular tractional retinal detachment were probably responsible for the final visual impairment, and intraocular tamponade affected the difference in visual prognosis between the groups of surgical indication. Multivariate analysis in all cases revealed that factors influencing visual outcome were preoperative rubeosis iridis and anemia. CONCLUSION: Rubeosis iridis and macular tractional retinal detachment were prognostic factors of the surgery. Vitrectomy for PDR may be effective in improving postoperative visual acuity if performed in the early stage of progressive fibrovascular proliferation in the posterior fundus after sufficient retinal photocoagulation.     

Experimental posterior penetrating eye injury in the rabbit. II. Histology of wound, vitreous, and retina.

The histological findings of the wound, the vitreous, and the retina in the rabbit eye with experimental posterior penetrating injury are described. Wound healing had just begun at 3 days after injury and was well established by 9 to 12 days. It involved proliferation of cells from the episclera and from the choroid. The progression to a fibrous ingrowth from the wound occurred only in eyes with blood in the vitreous. The intravitreal fibroblastic proliferation had begen at 6 days after injury and seemed to be derived from the choroid, the nonpigmented ciliary epithelium and, posteriorly, from the optic nervehead. During the development of retinal detachment the configuration of the peripheral and posterior retina, together with the orientation of vitreous strands, suggested the presence of vitreous traction. We postulate that the presence of contractile fibroblasts (myofibroblasts) in the vitreous may provide the mechanism for vitreous traction. The retinal detachments were also characterised by epiretinal and subretinal membranes, but these were not prominent. The end-stage appearance of a soft, shrunken eye with cyclitic membrane formation and retinal detachment resembles the outcome in many human eyes after severe penetrating injuries.     

23G玻切术治疗PDR术后早期出血的危险因素分析

目的：分析23G玻璃体切割术治疗增生型糖尿病视网膜病变(PDR)术后早期发生出血的危险因素。

方法：回顾性分析2016-06/2018-01于我院行23G玻璃体切割术治疗的PDR患者100例100眼的临床资料,根据术后早期(1mo内)是否发生玻璃体出血分为早期玻璃体出血组(27例)和无玻璃体出血组(73例),分析术后早期发生玻璃体出血的危险因素。

结果：两组患者年龄、术前抗VEGF治疗、术前存在纤维血管膜增殖、术中视盘新生血管出血、术中注入气体情况有明显差异(P<0.01),其中术前存在纤维血管膜增殖、术中存在视盘新生血管出血是导致术后早期出血的独立危险因素。

结论：23G玻璃体切割术治疗PDR术后早期玻璃体出血主要发生于眼底病变严重者,术前存在纤维血管膜增殖及术中视盘新生血管出血会增加其发生风险。     

Anterior hyaloidal fibrovascular proliferation after diabetic vitrectomy

Vitrectomy was performed to treat 74 consecutive eyes for complications of diabetic retinopathy. Eight (13%) of 61 eyes followed up for an average of 12 months developed anterior hyaloidal fibrovascular proliferation. This was the most common postoperative complication, whose features included recurrent hemorrhages into the vitreous cavity or anterior vitreous, or both; vessels or fibrovascular tissue on the posterior lens capsule; anterior extraretinal vascularization extending toward the lens on the anterior hyaloid; traction detachment of the peripheral retina or ciliary body; and hypotony. Patients who developed this complication tended to be young males with severe retinal neovascularization and extensive retinal ischemia; traction retinal detachment as an indication for surgery; placement of a scleral buckle; postoperative rubeosis iridis, recurrent vitreous hemorrhages, and retinal detachment; and multiple surgeries. Four eyes progressed to atrophia bulbi. Early recognition followed by additional surgery in two patients and extensive additional photocoagulation in two other patients was successful in preserving good visual function.     

糖尿病视网膜病变玻璃体切除术后玻璃体出血的临床分析

目的 探讨糖尿病视网膜病变(DR)玻璃体切割手术后玻璃体积血的原因，处理措施以及对预后的影响。 方法 回顾性分析98例DRⅣ期患者122只眼行玻璃体手术治疗后发生玻璃体积血25只眼的临床资料。 结果 玻璃体切割手术后发生玻璃体积血占本组玻璃体切割手术患者的20.5%。积血发生在手术后1周内者8只眼，1周至1个月者6只眼，1个月以上者11只眼。25只眼中C₃ F₈填充眼占31.1%,硅油填充眼占6.1%；空气填充眼占33.3%；灌注液填充眼占26.3%。视网膜周边部新生血管增生9只眼。3只硅油填充眼中2只眼积血自行吸收，1只眼局部形成视网膜前膜，在硅油取出同时行前膜剥除；22只非硅油填充眼中6只眼积血自行吸收；2只眼积血加重，但未及时处理，1只眼发生新生血管性青光眼，1只眼广泛玻璃体视网膜增生脱离，视力无光感；14只眼观察2周积血无吸收后进行了再次手术治疗，12只眼1次手术处理后未再积血。随访结束时，视力无光感者3只眼，手动者2只眼，数指～0.1者10只眼，0.3及以下者4只眼，0.3以上者6只眼。 结论 DR玻璃体切割手术后发生玻璃体积血的患者多数有周边部新生血管增生，经过及时手术治疗，预后较好。 (中华眼底病杂志,2007,23:241-243)     

Familial exudative vitreoretinopathy.

At age 26 years a woman who had been blind in the left eye from birth had visual acuity of R.E.: 6/18 (20/60); L.E.: 6/120 (20/400), with 40 prism diopters of left exotropia. The left eye showed a decreased anteroposterior diameter of the globe and a complete retinal detachment behind a cataractous lens. The right eye had a posterior subcapsular lens opacity severe vitreous fibrosis, dragging of the optic disk, and intraretinal and subretinal exudation with a fibrovascular mass in the temporal retina. The patient's 3-year-old daughter had 45 to 50 prism diopters of exotropia, a pendular nystagmus with intraretinal and subretinal dragging of each disk, and early degeneration and band formation in the periphery of each fundus.     

Pars plana incisions of four patients: histopathology and electron microscopy.

The pathology of pars plana incisions of four patients is described: three with light microscopy and one with light and electron microscopy. Two eyes were removed because of choroidal melanoma, immediately and 8 days after vitrectomy and transvitreous retinal biopsy. Considerable disruption of tissues surrounding the pars plana incisions was observed. Vitreous was incarcerated in the wounds, which healed with granulation tissue. One eye was examined 4 months after vitrectomy for diabetic retinopathy and a failed pars plana filtering operation. It contained fibrovascular ingrowth from all the incisions, infiltrating the vitreous base with granulation tissue and causing vitreous haemorrhage and retinal detachment. One eye was removed 1 year after vitrectomy for anterior hyaloidal fibrovascular proliferation and early phthisis. The wound had fibrous ingrowth histologically and evidence of active fibroplasia.