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.     

Contribution of posterior hyaloid membrane to pathogenesis and transciliary surgery of proliferative diabetic retinopathy

Results of 276 transcilliary vitrectomies in patients with proliferative diabetic retinopathy are analyzed. The indications for surgery were traditional in 180 patients and early in 98. The object of surgical manipulations in early surgery for proliferative diabetic retinopathy is the posterior hyaloid membrane, which should be detached from the retina and removed at an area as larger as possible. New vessels or fibrovascular tissue are left intact. After removal of the posterior hyaloid membrane they do not proliferate. Early surgery on the posterior hyaloid membrane in patients with proliferative diabetic retinopathy helps attain more stable and better functional results and involves a lesser number of serious intra- and postoperative complications. Fibrovascular proliferation does not progress after removal of the posterior hyaloid membrane at the site of the posterior pole of the eye, and therefore, we did not carry out panretinal laser coagulation during or after surgery. The only exceptions were cases with neovascularization of the iris in the postoperative period.     

Neovascularization from scleral wound as cause of vitreous rebleeding after vitrectomy for proliferative diabetic retinopathy

PURPOSE: To determine the site of rebleeding into the vitreous after vitrectomy in patients with diabetic retinopathy. METHODS: We studied in detail 4 eyes of 4 patients in whom rebleeding into the vitreous followed successful vitrectomy for proliferative diabetic retinopathy. In addition, the fibrous membrane removed at surgery was studied by light and electron microscopy. RESULTS: In these 4 eyes, the second operation revealed that the source of the vitreous rebleeding was from a fibrovascular proliferation around the scleral wounds of the initial surgery, and no other neovascularization and/or reproliferation were observed in the whole retina. Rebleeding in these 4 eyes developed at an average of 9 weeks after initial surgery. The proliferative membrane was oval in shape and expanded from the residual vitreous that had been incarcerated in the scleral wound. The proliferative membrane removed during vitrectomy was poor in cellular components and contained extracellular matrix. Blood vessels of various sizes were also present. Electron microscopy showed the membrane was rich in extracellular components and contained high and low electron density cells. These cells often had microvilli and seemed to be of epithelial origin. CONCLUSIONS: These findings show that vitreous rebleeding may develop from fibrovascular proliferation from the scleral wound created during initial surgery. The proliferated membrane showed histological similarities with the fibrovascular proliferation usually seen in the diabetic retina and may represent a type of anterior proliferation secondary to retinal ischemia.     

糖尿病玻璃体性状特点及其与增殖性糖尿病视网膜病变的关系

糖尿病患者体内持续的高血糖及相应的病理状态不仅会导致糖尿病视网膜病变(DR)，也会影响玻璃体代谢，导致糖尿病玻璃体病变。由于玻璃体与视网膜在解剖位置上毗邻，因此糖尿病玻璃体病变与DR在发生发展方面相互促进，特别是玻璃体后脱离(PVD)和玻璃体劈裂等玻璃体视网膜界面的改变，为纤维血管增殖膜的生长提供了支架，并与玻璃体切割术(PPV)术中操作密切相关。本文整理了糖尿病患者玻璃体结构及胶原交联产物改变、玻璃体视网膜界面改变及其与增殖性糖尿病视网膜病变(PDR)关系的相关研究，旨在深入了解糖尿病玻璃体病变，为DR的研究和治疗、PPV手术方案的制定等提供参考。     

Refinements in microinstrumentation for vitreous surgery

We developed a series of 25-gauge (0.5 mm) microinstruments for vitreous surgery, including a 25-gauge vitreous cutter, 25-gauge microscissors for limited reuse, and a vitreous membrane dissector. Clinical experience with these instruments in more than 20 cases of advanced proliferative vitreoretinopathy, retinopathy of prematurity, and diabetic retinopathy indicates that these instruments facilitate delicate vitreoretinal dissections, particularly in the vitreous base and when fibrovascular tissues are closely adherent to the retina. Because of their smaller size, the microinstruments are more precise in their cutting capabilities than other instruments.     

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.     

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.     

Elevation of vitreous leptin in diabetic retinopathy and retinal detachment

PURPOSE: Leptin is a cytokine that regulates energy metabolism and is linked to diabetes mellitus through its metabolic actions. Leptin is angiogenic and promotes wound healing, and therefore this investigation was conducted to determine whether leptin is associated with neovascular and fibrotic complications of diabetes and other retinopathies. METHODS: Serum and vitreous samples were collected from patients classified by the presence and type of diabetic retinopathy or other ocular diseases. Leptin was measured in serum and vitreous by radioimmunoassay, and leptin and leptin receptor were localized in epiretinal membranes immunohistochemically. RESULTS: Leptin levels in serum and vitreous were higher in patients with diabetes than in those without, and vitreous leptin concentrations were especially elevated in patients with proliferative diabetic retinopathy or retinal detachment. Leptin and leptin receptor were detected in fibrovascular epiretinal membrane of patients with diabetes. CONCLUSIONS: Leptin in human vitreous is elevated in proliferative diabetic retinopathy, and retinal detachment and is present in fibrovascular epiretinal tissue. These data suggest an involvement of leptin in retinal disease.     

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。     

Surgically induced detachment of the anterior hyaloid membrane from the posterior lens capsule

Vitreous hemorrhage adhering to the posterior lens capsule prevents adequate visualization of the vitreous cavity and fundus during vitreous surgery and during the dissection of fibrovascular membranes. This type of hemorrhage is difficult to remove by aspiration or resection using a vitreous cutter. We have developed a new technique designed to detach surgically the anterior vitreous for the removal of hemorrhage in patients with proliferative diabetic retinopathy. In this hydrodissection technique, the anterior vitreous is detached from the posterior lens capsule by a forced injection of infusion fluid into the anterior chamber. This technique separates the vitreous hemorrhage adhering to the posterior lens capsule and allows its removal.     

Combining phacoemulsification with pars plana vitrectomy in patients with proliferative diabetic retinopathy: a series of 223 cases

PURPOSE: To describe the results of combined phacoemulsification, insertion of posterior chamber intraocular lens (PCIOL), and pars plana vitrectomy for patients with retinal disorders resulting from diabetic retinopathy. DESIGN: Retrospective, consecutive, noncomparative, interventional case series. PARTICIPANTS: Two hundred twenty-three patients with vitreoretinal disorders secondary to diabetic retinopathy. METHODS: A case series of 223 consecutive patients with retinal disorders resulting from diabetic retinopathy who underwent combined phacoemulsification, insertion of PCIOL, and pars plana vitrectomy. MAIN OUTCOME MEASURES: Vision, number of secondary procedures, and complications. RESULTS: Two hundred twenty-three patients (153 with vitreous hemorrhage, 58 with traction retinal detachment, and 12 with macular traction) underwent combined surgery. The average increase in vision was 4.3 Snellen lines. The average follow-up was 10 months. Retinal detachment occurred in 5% of patients who underwent surgery. Diabetic macular edema was found in 12% after combined surgery. Cystoid macular edema was found in 3%. Vitreous hemorrhage requiring another procedure occurred in 11%. Twenty-two patients (10%) required a repeat vitrectomy (12 for vitreous hemorrhage and 10 for retinal detachment). CONCLUSIONS: Combined phacoemulsification, insertion of PCIOL, posterior capsulectomy, and pars plana vitrectomy can be used to treat patients with complications resulting from proliferative diabetic retinopathy. Combined surgery may prevent a second operation for postvitrectomy cataract, allowing earlier visual rehabilitation.     

Antiangiogenic drugs and advanced proliferative diabetic retinopathy

Advanced diabetic retinopathy with tractional retinal detachment or persistent vitreous hemorrhage often requires surgical treatment with pars plana vitrectomy. Despite advances in vitrectomy, surgery for complications of diabetic retinopathy can be a challenge and may be impaired by intense fibrovascular proliferation. Antiangiogenic drugs have been used for the treatment of diabetic retinopathy because of their inhibitory action on vascular endothelial growth factor. In this review, we discuss aspects related to the adjuvant use of these drugs in vitrectomy for complications of diabetic retinopathy. Bevacizumab shows beneficial effects regarding the surgical technique facilitation, but its long-term benefit still needs to be studied.     

增生型糖尿病视网膜病变玻璃体切除手术后再出血病因及治疗

目的 分析增生型糖尿病视网膜病变(PDR)玻璃体切割手术后再出血病因，观察再治疗效果。 方法 回顾分析302例PDR患者315只患眼接受玻璃体切割手术治疗后32只眼再出血并再次治疗后随访3~48个月（平均随访时间12个月）的临床资料。 结果 PDR玻璃体切割手术后再出血发生率为10%，再出血发生时间为手术后1～210 d，平均时间为51 d。再出血的主要原因中，28%为巩膜切口纤维血管向内生长，19%为视盘表面残存新生血管膜或血管残端处理不当，22%为视网膜激光光凝不足，9%为视网膜表面新生血管膜剥除不彻底，6%为视网膜静脉阻塞，16%为外力作用。通过冷凝巩膜切口处纤维血管、剥离视盘和视网膜表面残存新生血管膜并电凝视盘表面血管残端、补充视网膜激光光凝、 包扎双眼等治疗，再出血眼视力提高者占91%，视力下降者占9%。再次手术后并发症主要包括再次出血、虹膜后粘连、晶状体混浊加重、角膜上皮愈合延迟等。 结论 PDR玻璃体切割手术治疗后再出血的主要原因是巩膜切口纤维血管向内生长、视盘表面和（或）视网膜表面新生血管膜剥除不彻底、血管残端处理不当、视网膜激光光凝不足和外力作用。处理好巩膜切口、彻底剥离视盘和视网膜表面新生血管膜、电凝血管残端以及足够的视网膜激光光凝是预防和治疗PDR玻璃体切割手术后再出血的有效方法。(中华眼底病杂志,2007,23:238-240)      

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.     

Proliferative diabetic retinopathy: vitreo-retinal complications are often related to insufficient retinal photocoagulation

INTRODUCTION: Panretinal photocoagulation proved to be effective in preventing complications related to vasoproliferative diabetic retinopathy. Surgery is most often a last resort in cases of recurrent or persistent vitreous hemorrhage or retinal detachment. The aim of our study is to point out that eyes requiring surgery for complications related to vasoproliferative diabetic retinopathy are often insufficiently photocoagulated. PATIENTS AND METHODS: Retrospective analysis of operating protocols and surgical results for a series of 39 eyes of 36 patients with complications of vasoproliferative diabetic retinopathy. RESULTS: The mean age at the intervention was 57 years. Eighty-five percent of the eyes had a vitreous hemorrhage, 17% a retinal detachment. Eighty-five percent of the eyes had undergone a partial retinal photocoagulation before surgery. All eyes underwent a vitrectomy with segmentation of fibrovascular membranes. In 85% of the eyes studied, endolaser photocoagulation was necessary, sometimes even in the mid-periphery. After 39+/-26 months of postoperative follow-up, 97% of eyes showed improvement of the anatomical state of the retina and improvement or stabilization of visual acuity. CONCLUSION: Our results confirm the benefit of vitreoretinal surgery in complications related to vasoproliferative diabetic retinopathy. Moreover, it should be emphasized that complications requiring surgery often result from incomplete preoperative photocoagulation. To be effective, photocoagulation has to destroy more than 35% and up to 50% of photoreceptors. An intraoperative laser extension can reduce the risk of regrowth of fibrovascular membranes.     

玻璃体积血的形态结构与玻璃体后脱离的图像特征

目的探讨玻璃体积血的形态结构和治疗特点.方法对74例(79只眼)增生性糖尿病视网膜病变、视网膜血管炎、视网膜静脉阻塞所致玻璃体积血的临床资料进行比较分析.术前超声检查、术中手术显微镜观察患者的玻璃体形态特点,分析玻璃体与视网膜的关系.结果所有患者均有不同程度的玻璃体后脱离,根据图像的形态特征可归纳为完全后脱离和部分后脱离两种.部分后脱离又分为"V"型、"L"型及后部玻璃体劈裂型,劈裂型多见于视网膜缺血性疾病的增生期.结论了解和掌握玻璃体后脱离及玻璃体劈裂的形态特点,可提高手术治疗的成功率并改善其预后.     

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.     

TPA-assisted vitrectomy for proliferative diabetic retinopathy: results of a double-masked, multicenter trial.

OBJECTIVE: Some complications of vitrectomy are related to adherence of the vitreous body to the retina. We studied whether these complications could be decreased by injecting a proteolytic enzyme, tissue plasminogen activator (TPA), at the beginning of surgery to aid separation of the vitreous from the retina. METHODS: Fifty-six patients receiving surgery for complications of proliferative diabetic retinopathy were divided into two groups in this prospective, randomized, double-blind study. Group I patients received 25 microg of intravitreal TPA in buffered salt solution (BSS) 15 minutes before vitrectomy. Group II received BSS alone. Postoperative follow-up lasted up to 3 months. The major criteria for comparison were the number of perioperative iatrogenic tears, the gain in visual acuity, and the reattachment rate of tractional retinal detachments. RESULTS: No difference was found between the two groups for the principal indicators or for complications. CONCLUSION: In proliferative diabetic retinopathy, the use of 25 microg of TPA by intravitreal injection 15 minutes before vitrectomy does not improve the results. No specific complications of the method were noted. The failure can be attributed to a too-short delay between TPA injection and beginning of surgery, an insufficient dose, or an insufficient quantity of plasminogen in the vitreous at the beginning of the intervention.     

Ultrasound biomicroscopy of sclerotomy sites after pars plana vitrectomy for diabetic vitreous hemorrhage

OBJECTIVE: This study was aimed at assessing changes at the sclerotomy site using the ultrasound biomicroscope (UBM) in eyes that underwent primary pars plana vitrectomy for complications of proliferative diabetic retinopathy. DESIGN: Prospective, observational case series. PARTICIPANTS: Eighty-six eyes of 84 patients with vitreous hemorrhage caused by proliferative diabetic retinopathy. INTERVENTION: Three-port pars plana vitrectomy followed by UBM evaluation of all sclerotomy sites between 6 and 8 weeks after surgery. Correlation with intraoperative findings done in case of reoperations. Forty-one eyes had repeat UBM at 6 months. MAIN OUTCOME MEASURES: The changes at the sclerotomy site were classified into six groups: well healed, gape, plaque, vitreous incarceration, fibrovascular proliferation, and anterior hyaloidal fibrovascular proliferation (AHFVP). The UBM characteristics of each of the groups were defined. The findings at 6 months were compared with those at 6 to 8 weeks. RESULTS: At 6 to 8 weeks after surgery, most sclerotomies were well healed or had either moderate to high reflective plaques bridging the site. Wound gape was seen in 22.1% of active ports, 32.6% of light ports, and 25.6% of infusion ports. Vitreous incarceration was seen most often at the infusion port (18. 6% of eyes). Fibrovascular proliferation was seen in 9.3% of active ports, 12.8% of light ports, and 15.1% of infusion ports. Thirteen eyes had recurrent vitreous hemorrhage 6 to 8 weeks after surgery. Cases with rebleeding and no fibrovascular proliferation at the sclerotomy on UBM did well with outpatient fluid-air exchange (two eyes) or observation only (three eyes). Those with fibrovascular proliferation on UBM (eight eyes) required more extensive surgery. CONCLUSIONS: UBM is helpful in detecting complications at the sclerotomy sites after pars plana vitrectomy and is an invaluable tool in the assessment of the patient before reoperation.     

VEGF localisation in diabetic retinopathy

AIM—To determine the staining pattern of vascular endothelial growth factor (VEGF) at different stages of diabetic retinopathy (including post-laser photocoagulation) and to compare staining in excised fibrovascular and fibrocellular (non-diabetic) preretinal membranes.
METHODS—Immunohistochemical localisation of VEGF, using antibodies raised against VEGF₁₆₅ and VEGF_121,165,189, was carried out on specimens of normal human retina (n=15), diabetic retinas ((a) with no overt retinopathy (n=19), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n=6), (c) with active proliferative retinopathy (n=6), (d) with no residual proliferative retinopathy after photocoagulation therapy (n=15)), excised diabetic fibrovascular membranes (n=19), and non-diabetic fibrocellular membranes (n=7). The degree and pattern of immunostaining was recorded.
RESULTS—In general, VEGF was absent from the majority of normal retinas. VEGF staining was apparent in most diabetic tissues but the staining pattern was dependent on both the specificity of the antibody used and the category of tissue. Staining with the VEGF₁₆₅ antibody was generally confined to endothelial cells and perivascular regions while the VEGF_121,165,189 antibody was also associated with extravascular components of the inner retina. Intensity of immunostaining of diabetic eyes was dependent on the severity of retinopathy being least in diabetics with no overt retinopathy and greatest in retinas with proliferative retinopathy. Interestingly, the intensity of immunostaining in diabetic retinas which had undergone laser surgery for proliferative retinopathy was reduced to basal levels. Moderate to intense immunostaining was observed in all fibrovascular and fibrocellular membranes examined.
CONCLUSIONS—This study supports a circumstantial role for VEGF in the pathogenesis of both the preclinical and proliferative stages of diabetic retinopathy.

Keywords: vascular endothelial growth factor; VEGF; diabetes; diabetic retinopathy