Retina-specific expression of PDGF-B versus PDGF-A: vascular versus nonvascular proliferative retinopathy

PURPOSE: Platelet-derived growth factor (PDGF) has been implicated in vascular proliferative retinopathies, such as diabetic retinopathy, and in nonvascular retinopathies, such as proliferative vitreoretinopathy. Traction retinal detachment is a central feature of both types of disease. Hemizygous rhodopsin promoter/PDGF-B (rho/PDGF-B) transgenic mice exhibit proliferation of vascular cells, glia, and retinal pigmented epithelial (RPE) cells, resulting in traction retinal detachment. Hemizygous rho/PDGF-A transgenic mice show mild proliferation of glial cells and no traction retinal detachments. This study was undertaken to determine whether higher levels of endogenously produced PDGF-A in the retinas of mice result in retinal detachment. METHODS: To achieve high-level expression of PDGF-A in the retina, homozygous rho/PDGF-A (rho/PDGF-AA) mice were generated. The phenotype of these mice was compared with that of homozygous rho/PDGF-B (rho/PDGF-BB) mice and double hemizygous rho/PDGF-B-rho/PDGF-A (rho/PDGF-AB) mice. RESULTS: Rho/PDGF-BB and rho/PDGF-AB mice showed a phenotype similar to that previously described in rho/PDGF-B mice. There was extensive proliferation of glial and vascular cells, resulting in fibrovascular membranes that detached the retina. PDGF-AA mice showed extensive proliferation of glial cells and traction retinal detachment. CONCLUSIONS: High retinal expression of PDGF-A results in extensive proliferation of glial cells and traction retinal detachment without vascular cell involvement, similar to proliferative vitreoretinopathy in humans. High retinal expression of PDGF-B results in traction retinal detachment from proliferation of both vascular and nonvascular cells, similar to diabetic retinopathy in humans.     

Chronic retinopathy of prematurity

A pathologic analysis of 40 autopsy cases of chronic retinopathy of prematurity is presented. The type of retinal detachment in chronic retinopathy is unique, resulting from progressive changes in the peripheral retina: folding at the site of extraretinal vasoproliferation; scroll-like rolling anteriorly towards the lens; foreshortening of entire retina with detachment; and closure of the retinal "funnel." The biomechanical intraretinal and extraretinal factors operating during this process are discussed. Also presented are some interesting atypical features found in this series: arrested retinopathy; "sea fan" extraretinal vascular fronds; retinopathy in anencephaly; cribriform vanguard; and extramedullary erythropoiesis.     

A review of the role of glial cells in understanding retinal disease

Retinal vascular diseases such as diabetic retinopathy and retinopathy of prematurity are major causes of visual loss. Although the focus of a great deal of research has been on the aetiology of vascular growth, it is now emerging that anomalies in other retinal cell types, especially glial cells, occur very early in the course of the disease. Glial cells have major roles in every stage of disease, from the earliest subtle variations in neural function, to the development of epi‐retinal membranes and tractional detachment. Therefore, having a firm understanding of the function of retinal glia is important in our understanding of retinal disease and is crucial for the development of new treatment strategies.     

Description and pathogenesis of late stages of retinopathy of prematurity

The retinal and vitreous changes seen in retinopathy of prematurity (ROP) can be explained by proliferation and contraction of tissue originating in the shunt area. Avascular retina is stretchable, and therefore much of it stays attached, while vascular retina is nonstretchable and detaches. When the shunt area forms a circular ring, one of three distinct patterns of retinal detachment develops, according to whether the shunt area is anterior, equatorial, or posterior in location. The detachments of ROP are, typically, traction detachments.     

Exudative retinopathy of adults: a late sequela of retinopathy of prematurity

The cases of 11 patients with a unilateral, retinal detachment associated with hard exudate and other late sequelae of retinopathy of prematurity are described. The abnormality was first noted in the second to fourth decades of life. Ten of the patients were women and one was a man. The source of the hard exudate was thought to be telangiectatic retinal vascular abnormalities. Among the ten treated eyes, four demonstrated an improvement in visual acuity. In two cases a mass lesion was also noted in the fundus.Supported in part by the Retina Research and Development Fund, Philadelphia, and Research to Prevent Blindness, New York     

Cytokeratin-containing cells in proliferative diabetic retinopathy membranes.

Immunohistochemical techniques were used to investigate the relation between retinal pigment epithelial cells (RPE), traction retinal detachment (TRD) membranes, and combined traction rhegmatogenous retinal detachment (CTR) membranes in proliferative diabetic retinopathy. Seven CTR and five TRD membranes were obtained during closed microsurgery. Six of the seven CTR membranes and one of the five TRD membranes contained RPE. Eleven of the 12 diabetic membranes incorporated glial cells. The findings emphasise that the intravitreal membranes of proliferative diabetic retinopathy contain a diversity of cell types and indicate that RPE tend to contribute to CTR, rather than TRD, membranes. The histopathological appearance of CTR membranes is that of a hybrid between TRD and proliferative vitreo-retinopathy membranes.     

A case of proliferative sarcoid retinopathy with sarcoid nodules in tissue obtained during vitrectomy

BACKGROUND: In previous studies, intraocular proliferative tissues obtained from proliferative sarcoid retinopathy cases during vitrectomy have been examined histopathologically. However, there is no report of identification of sarcoid nodules in examined tissues. We performed vitrectomy for a case of proliferative sarcoid retinopathy with extensive proliferative changes. Histopathologically, sarcoid nodules were identified in the fibrovascular membranes. CASE: A 25-year-old man was treated for sarcoid uveitis in the right eye by his local ophthalmologist. Lens aspiration was performed for complicated cataract. He was referred to our hospital with vitreous opacity and traction retinal detachment which occurred after the surgery. FINDINGS: The vitreous opacity was so severe that details of the fundus were not visible. Traction retinal detachment was suspected from findings of B-mode echography. Vitrectomy was performed, and total retinal detachment due to contraction of the fibrovascular membrane around the optic disc and posterior pole was observed. Sarcoid nodules were identified histopathologically in fibrovascular membranes obtained during vitrectomy. CONCLUSION: In proliferative sarcoid retinopathy cases, sarcoid lesions may be one of the causes of fibrovascular membrane formation.     

A Case of Proliferative Sarcoid Retinopathy with Sarcoid Nodules in Tissue Obtained During Vitrectomy

Background: In previous studies, intraocular proliferative tissues obtained from proliferative sarcoid retinopathy cases during vitrectomy have been examined histopathologically. However, there is no report of identification of sarcoid nodules in examined tissues. We performed vitrectomy for a case of proliferative sarcoid retinopathy with extensive proliferative changes. Histopathologically, sarcoid nodules were identified in the fibrovascular membranes.Case: A 25-year-old man was treated for sarcoid uveitis in the right eye by his local ophthalmologist. Lens aspiration was performed for complicated cataract. He was referred to our hospital with vitreous opacity and traction retinal detachment which occurred after the surgery.Findings: The vitreous opacity was so severe that details of the fundus were not visible. Traction retinal detachment was suspected from findings of B-mode echography. Vitrectomy was performed, and total retinal detachment due to contraction of the fibrovascular membrane around the optic disc and posterior pole was observed. Sarcoid nodules were identified histopathologically in fibrovascular membranes obtained during vitrectomy.Conclusion: In proliferative sarcoid retinopathy cases, sarcoid lesions may be one of the causes of fibrovascular membrane formation.     

Laser photocoagulation in preproliferative retinopathy of incontinentia pigmenti.

Incontinentia Pigmenti is a rare, X-linked, dominant disorder in which affected female infants develop characteristic abnormalities of the skin, central nervous system, hair, teeth, and eyes. Ocular abnormalities occur in about 35% of patients and consist of proliferative vitreoretinopathy, retinal detachment, strabismus, cataract, microphthalmia, optic nerve atrophy, and iris hypoplasia. Retinal vascular abnormalities, ranging from peripheral retinal avascularity to neovascular and fibrous proliferation with traction retinal detachment, are the primary cause of severe visual dysfunction in patients. Therapeutic intervention with laser photocoagulation and cryotherapy for the proliferative vitreoretinopathy of incontinentia pigmenti has met with variable success. We report a case in which laser photocoagulation was used at the onset of retinopathy with subsequent resolution of the vasculopathy.     

Outcome of prematurity and retinopathy of prematurity

Retinopathy of prematurity is a disease that manifests soon after birth in the premature infant and may lead to a lifelong disability. More infants at risk for developing the retinopathy are surviving, and the ophthalmologist must be aware of possible vision abnormalities, such as decreased acuity, strabismus, nystagmus, retinal scarring, and retinal detachment, that occur during childhood and in adult life. These abnormalities may occur in children who developed only mild forms of retinopathy of prematurity during early life.     

Criswick-Schepens-Syndrom — Familiäre exsudative Vitreoretinopathie

BACKGROUND: Familial exudative vitreoretinopathy is a hereditary, bilaterally progressive formation of a vitreoretinal membrane. It usually occurs in full-term newborns without previous treatment with hyperbaric oxygen. In this report, we present six cases of this disease with various abnormalities of the posterior segment diagnosed in two Syrian families related by first degree of consanguinity. DESIGN: A retrospective family analysis and presentation of cases. CASE PRESENTATION: Six members of the two consanguineous families, aged between 3.5 and 13 years, who were systemically healthy, presented with a visual acuity ranging between light perception and 0.4 with bilateral fundus changes. The findings included: papillary, macular, and retinal temporal traction in 11 eyes, a retinal fold in 7 eyes, a fibrovascular mass in 11 eyes, vitreoretinal traction in 5 eyes, subretinal exudation in 2 eyes, pigmentary abnormalities in 2 eyes, temporal or total tractional retinal detachment in 2 eyes, and vitreous hemorrhage in 1 eye. SUMMARY: Familial exudative vitreoretinopathy is characterized by fundus changes that resemble retinopathy of prematurity and must be differentiated from other diseases (e.g., Coats' disease, incontinentia pigmenti, persistent hyperplastic primary vitreous, and Norrie's disease).     

Ⅱ型增殖性糖尿病视网膜病变患者行玻璃体切除地机与术后视力 …

探讨Ⅱ型增殖性糖尿病视网膜病变合并严重玻璃本出血或合并血管纤维增殖引起的视网膜牵拉性视网膜脱离情况下,进行玻璃全切除术的手术时机。     

进展型增生性糖尿病视网膜病变玻璃体 切割手术的价值与意义

目的了解有不同并发症的进展型增生性糖尿病视网膜病变眼进行玻璃体手术的结果。方法将患有Ⅰ、Ⅱ型糖尿病进展型增生性糖尿病视网膜病变的314只眼分为玻璃体积血合并局限牵拉性视网膜脱离组;广泛纤维血管膜合并牵拉性视网膜脱离组;牵拉孔源混合性视网膜脱离组;玻璃体积血视网膜脱离合并老年性白内障行玻璃体手术联合白内障摘除及人工晶状体植入组,分别进行回顾性分析。结果玻璃体积血合并局限牵拉性视网膜脱离组中Ⅰ、Ⅱ型糖尿病患 者手术后获得0.1以上视力的分别占39.4%和66.7%,广泛纤维血管膜合并牵拉性视网膜脱离组中Ⅰ、Ⅱ型糖尿病患者手术后获得0.1以上视力的分别占31.6%和51.6%,牵拉孔源混合性视网膜脱离组手术后获得0.1以上视力者占31.6%,玻璃体积血视网膜脱离合并老年性白内障行玻璃体手术联合白内障摘除及人工晶状体植入组手术后获得0.1以上视力者占62.5%。首要的术中 并发症是医源性视网膜裂孔,术后视力丧失的主要原因包括新生血管性青光眼、视网膜脱离和视网膜中央动脉阻塞。结论玻璃体切割手术联合全视网膜光凝术,能有效地改善进展性糖尿病视网膜病变患者的视力。(中华眼底病杂志,2001,17:171-174)     

糖尿病视网膜病变合并白血病的诊疗进展

白血病是加重糖尿病视网膜病变（DR）的危险因素。DR合并白血病的患者常首诊于眼科,其眼底除了会出现视网膜静脉纡曲扩张、微动脉瘤和视网膜出血、渗出等典型DR表现,还会合并罗斯斑等白血病视网膜病变的表现。其在微血管异常轻微的病变早期就可能出现大量视网膜血管无灌注区及新生血管,同时玻璃体积血、纤维血管增生膜及牵引性视网膜脱离...     

Expression of ephrinB2 and its receptors on fibroproliferative membranes in ocular angiogenic diseases

PURPOSE: To determine whether ephrinB2 plays a role in ocular angiogenesis, we investigated the expression of ephrinB2 and EphB receptors on retinal fibroproliferative membranes. DESIGN: Experimental study of the expression of ephrinB2 and EphB receptors within fibroproliferative membranes in patients with ocular angiogenic diseases collected during vitrectomy. METHODS: Fibroproliferative membranes were obtained at the time of vitrectomy from 20 patients with proliferative diabetic retinopathy (PDR) and from 40 patients who had stage 5 retinopathy of prematurity. Specimens were investigated with immunohistochemistry using polyclonal antibodies directed against ephrinB2 and the EphB2, EphB3, and EphB4 receptors. Immunoreactivity for von Willebrand factor (factor VIII) and alpha-smooth muscle actin (alpha-SMA) was also determined to confirm the identity of the target vascular endothelial cells. RESULTS: Positive staining for ephrinB2 was observed on fibroproliferative membranes that were obtained from patients with PDR (65.0%) and retinopathy of prematurity (25.0%). Specifically, ephrinB2 was found to be present on endothelial cells, as confirmed by its colocalization with factor VIII and alpha-SMA staining. EphB2 and EphB3 expression was observed on fibroproliferative membranes that were harvested from patients with PDR (EphB2, 90.0%; EphB3, 70.0%) and retinopathy of prematurity (EphB2, 35.0%; EphB3, 45.0%). However, EphB4 expression was not observed in any of the membranes derived from patients with PDR or retinopathy of prematurity. The rate of ephrinB2 expression in patients with PDR was significantly higher than that seen in patients with retinopathy of prematurity, which probably reflected differences in the vascular density of their fibroproliferative membranes. CONCLUSION: These data suggest that the ephrinB2-EphB2/B3 system may play an important role in ocular angiogenesis.     

Echography of optic disc related pathology in diabetic retinopathy

Combined A- and B-scan examination of eyes with diabetic retinopathy and opaque media provides information about the presence and density of vitreous hemorrhages, can detect membranes inserting into the optic disc or the retina and differentiate them from retinal detachment. Absolute and relative indications for echographic examination are listed and some echograms concerning vitreous hemorrhage, proliferating membranes and traction retinal detachment are presented. The value of both A-scan standardized echography and contact B-scan technique for previtrectomy evaluation is stressed.     

Presumed exudative retinal detachment after cryotherapy in retinopathy of prematurity.

Cryotherapy of the peripheral avascular retina in selected cases of retinopathy of prematurity has been shown to reduce the incidence of posterior retinal detachment, retinal fold involving the macula, and retrolental tissue. Although exudative retinal detachments have been described after cryotherapy during scleral buckling procedures, to our knowledge, this observation has not been reported after cryotherapy in retinopathy of prematurity. We describe such a case.     

The treatment of advanced retinopathy of prematurity by cryotherapy and scleral buckling surgery

Seventeen eyes of nine extremely premature infants with severe acute proliferative retinopathy of prematurity (ROP, Grades III-V) were treated. Cryotherapy alone was used in ten eyes to ablate extensive areas of avascular retina to thereby induce involution of widespread intravitreous neovascularization. No attempt was made to directly treat the arteriovenous shunt or neovascularization itself. Scleral buckling surgery was used in combination with cryotherapy in seven additional eyes to relieve diffuse vitreous traction to intravitreous neovascularization which had caused extensive traction retinal detachment. Cryotherapy was uniformly successful in causing involution of widespread intravitreous neovascularization in all patients treated. Scleral buckling surgery was initially effective in reattaching the retina in all cases but late manifestations of severe ongoing vitreoretinal traction required additional open-sky vitrectomy in two eyes and resulted in inoperable recurrent total traction retinal detachment in one eye and extensive macular scarring in another. A comparison is made between the proliferative retinopathies seen in ROP and diabetes mellitus and a rationale for effective cryotherapy in ROP is presented. In our clinical experience, the single most important prognostic factor determining the potential severity of ROP is the width and extent of the retinal avascular zone. The wider the zone, the greater the probability of rapid progression from early to advanced grades of disease.     

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.     

Visual results and prognostic factors for vision following surgery for stage V retinopathy of prematurity

As our surgical techniques improve we are able to achieve anatomic retinal reattachment in 48% of eyes with advanced retinopathy of prematurity. Only 31% of these eyes, however, have achieved visual function by the six-month follow-up visit. In an attempt to determine the factors that lead to better visual outcome, we analyzed 85 eyes of 45 children who underwent surgical therapy for Stage V retinopathy of prematurity by one surgeon. These eyes were followed from 6 to 36 months. We analyzed the timing of surgery, retinal configuration, subretinal fluid composition, and appearance of retinal pigment epithelium following resolution of detachment as these related to visual results. We also used visual evoked response testing in an attempt to predict which eyes might achieve visual function. Children with best visual results tended to have rapidly regressing vascular activity, were operated earlier, and had little subretinal exudate sparing the macula and little alteration of RPE following retinal reattachment, and if measured, low iron concentration in subretinal fluid.