Viscosity of subretinal fluid and its clinical correlations

The viscosity of subretinal fluid is an important factor in transmitting force created by subretinal fluid motion to the retina. The variation of viscosity of subretinal fluid can explain variations in the effect of subretinal fluid motion on the retina. Pseudoplastic variation of subretinal fluid viscosity was confirmed using a cone-plate microviscometer. To explain the variability in viscosity between subretinal fluid specimens, 14 clinical variables associated with each of 46 specimens were examined. The strongest statistical relationship was between aphakia and lower viscosity.     

Fibronectin synthesis in subretinal membranes of proliferative vitreoretinopathy.

In situ hybridisation and immunohistochemical studies were conducted on six surgically excised subretinal membranes of proliferative vitreoretinopathy to investigate whether displacement of retinal pigment epithelial and glial cells to subretinal membranes was associated with fibronectin production by the subretinal membrane cells. Fibronectin messenger RNA (mRNA) and fibronectin immunoreactivity were observed in some cells in all of the subretinal membranes studied and up to 30% of the cells in individual specimens showed intense labelling for fibronectin mRNA. The results support the concept that the cells in subretinal membranes produce fibronectin. Locally produced fibronectin may play a role in subretinal membrane cohesion, and displacement of retinal pigment epithelial and glial cells from their normal location may induce the cells to manufacture fibronectin. Fibronectin production may be more prominent in migrating subretinal cells.     

Management of breakthrough vitreous hemorrhage from presumed extramacular subretinal neovascularization

Three patients developed vitreous hemorrhage secondary to breakthrough bleeding from presumed extramacular subretinal neovascularization. In one patient, the vitreous hemorrhage cleared spontaneously. In two other patients, trans-pars plana vitrectomy was performed. All patients regained 20/30 vision or better. Residual peripheral retinal pigment epithelial atrophy, organized subretinal hemorrhage, and/or subretinal fibrous membranes were present in all patients. A definite extramacular subretinal neovascular membrane was identified in one patient. Ocular diseases associated with subretinal neovascularization are tabulated. Indications for trans-pars plana vitrectomy in patients with breakthrough vitreous hemorrhage secondary to presumed extramacular subretinal neovascularization are proposed.     

Transforming growth factor beta(2) increases in subretinal fluid in rhegmatogenous retinal detachment with subretinal strands

PURPOSE: To compare transforming growth factor (TGF) beta(2) levels in subretinal fluid of rhegmatogenous retinal detachment with or without subretinal strand formation. METHODS: We assessed total and mature TGF-beta(2) levels in subretinal fluid obtained from 24 eyes with rhegmatogenous retinal detachment using an enzyme-linked immunosorbent assay. Group I comprised 18 specimens from eyes without subretinal strands, while group II comprised 6 specimens from eyes with subretinal strands. RESULTS: Total and mature TGF-beta(2) levels were higher in group II than in group I (p=0.01 and p=0.07, respectively). CONCLUSION: The concentrations of total and mature TGF-beta(2) were higher in cases of rhegmatogenous retinal detachment associated with subretinal strand formation compared to those without subretinal strand formation.     

Subretinal washout for subtle subfoveal hard exudates in diabetic macular edema

PURPOSE: To evaluate the efficacy of subretinal washout for subtle subfoveal hard exudates in diabetic macular edema. METHODS: This study was done retrospectively on a series of patients with diffuse diabetic macular edema accompanied with subtle subfoveal hard exudates and operated on by one surgeon(NO). Patients ranged in age from 30 to 76 years(mean, 59 years). The postoperative follow-up interval ranged from 12 to 76 months, with a mean of 35 months. Two groups were identified. The first group contained all 26 eyes that had vitreous surgery with subretinal washout. This was compared with a second group of 51 eyes without subretinal washout. We compared the rate of occurrence of postoperative massive foveal hard exudates, visual acuity results, and complications with and without subretinal washout. RESULT: There was no significant difference in base line demographics between the two groups. Massive foveal hard exudates did not occur in eyes with subretinal washout, but occurred in 29 (57%) of the eyes without subretinal washout(p < 0.0001) and in 15 eyes which had undergone reoperation with subretinal washout. Visual acuity improved in 54% of the subretinal washout eyes and 45% of the eyes without it. Visual acuity improved to 20/30 or better in 23% of the eyes with subretinal washout and in 8% of the eyes without subretinal washout. There was no serious complication related to subretinal washout. CONCLUSION: Subretinal washout for subtle subfoveal hard exudates in diabetic macular edema may prevent massive subfoveal exudates and improve visual results. Further study is needed to investigate the pathogenesis.     

Tissue plasminogen activator treatment of experimental subretinal hemorrhage

To determine if tissue plasminogen activator, a clot-specific fibrinolytic agent, could eventually be used to assist in the clearance or removal of subretinal hemorrhage, we studied the effect of subretinal injections of tissue plasminogen activator, autologous blood, balanced salt solution, and the combination of either tissue plasminogen activator or balanced salt solution after subretinal injection of autologous blood on retinal morphologic characteristics and clearance of subretinal hemorrhage in the albino rabbit. No morphologic evidence of tissue plasminogen activator toxicity was found in the rabbit retina at a dose of 25 to 50 micrograms/0.1 ml. Subretinal hemorrhage cleared faster after subretinal injection of tissue plasminogen activator when compared to balanced salt solution (P = .0005) but did not completely prevent overlying retinal degeneration. Both tissue plasminogen activator and balanced salt solution were found to decrease the toxic effects of subretinal blood on the morphologic characteristics of the rabbit retina, and this effect can be explained at least partly by dilution of the subretinal blood.     

Vitrectomy with circumferential peripheral retinotomy for massive subretinal hemorrhage

PURPOSE: To assess the effect of vitrectomy with circumferential peripheral retinotomy on massive subretinal hemorrhage. METHOD: Eight patients (8 eyes) with massive subretinal hemorrhage of more than 2 quadrants, underwent pars plana vitrectomy between May 2000 and February 2004. The average age was 73.5 years. Seven patients (7 eyes) were male, and one was female (1 eye). An average of 207.5 degree circumferential peripheral retinotomy was carried out for removal of subretinal hemorrhage. The amount of postoperative subretinal hemorrhage, the improvement of visual acuity, and postoperative complications were evaluated. RESULTS: Postoperatively, the volume of subretinal hemorrhage decreased in all cases. The visual acuity improved in 7 of the 8 eyes (87.5%). Postoperatively, none of the cases developed proliferative vitreoretinopathy, but subretinal hemorrhage recurred in 2 eyes. CONCLUSIONS: Vitrectomy with circumferential peripheral retinotomy may reduce massive subretinal hemorrhage and increase visual acuity.     

Fibrinolysis of experimental subretinal haemorrhage without removal using tissue plasminogen activator.

AIMS/BACKGROUND: Human recombinant tissue plasminogen activator (rt-PA) fibrinolysis of subretinal haemorrhage with concomitant removal has been shown to reverse the natural history of photoreceptor degeneration in experimental subretinal haemorrhages if evacuated within 7 days. The aim of the study was to determine whether fibrinolysis of subretinal haemorrhage without concomitant removal would offer a simpler approach with similar photoreceptor sparing. METHODS: A neodymium YAG laser was used to create experimental subretinal haemorrhages beneath the holangiotic retina of the cat. Tissue plasminogen activator (10 micrograms/ml) was injected into 4 day old subretinal haemorrhages to evaluate its effect on altering the natural history of retinal degeneration. Light and electron microscopy were used to study the histopathological effect. RESULTS: The injection of rt-PA into large 4 day old subretinal haemorrhages without concomitant removal did not alter the natural history of retinal degeneration. In fact, a second focus of retinal degeneration occurred at a gravity dependent inferior site where the subretinal haemorrhages had migrated. CONCLUSIONS: There was no therapeutic benefit from the injection of rt-PA into subretinal haemorrhages without con-comitant removal in this cat model.     

Nuclear magnetic resonance imaging of subretinal fluid

We ascertained the relationship between the relaxation time of magnetic resonance imaging and the protein concentration of subretinal fluid, by examining rhegmatogenous and nonrhegmatogenous retinal detachments with a 0.15 tesla nuclear magnetic resonance system, and we calculated T1 and T2 relaxation times of subretinal fluid. The protein concentration of subretinal fluid obtained at the time of surgery was determined by a biochemical method. The subretinal fluid in a fresh rhegmatogenous retinal detachment had a low protein concentration and relaxation times equal to those of vitreous. Conversely, increased protein concentrations and shortened relaxation times were noted in subretinal fluid from long-standing rhegmatogenous retinal detachments. Subretinal fluid in a nonrhegmatogenous retinal detachment with a high concentration of protein showed much shorter relaxation times. The relaxation times and protein concentration of the subretinal fluid correlated closely. It may be possible to measure the protein concentration of subretinal fluid in vivo with nuclear magnetic resonance imaging.     

A new instrument for drainage or injection of fluid within subretinal space

PURPOSE: To describe a new instrument, the subretinal aspiration and injection device (SR-AID), designed to facilitate the controlled external drainage or injection of fluid in the subretinal space. METHODS: The SR-AID is formed by an assembly of a probe, handle body, and a driving unit. The curved conduit within the probe segment forms a curved tunnel and acts as a guide along which a needle moves back and forth. The feasibility of fluid injection beneath the attached retina was tested in animal eyes. The efficacy of subretinal fluid drainage with the SR-AID were assessed in six cases of clinical retinal detachment. RESULTS: External approach to the subretinal space under ophthalmoscopic monitoring can be achieved by oblique angle penetration of the scleral wall with a needle from the SR-AID. Fluid was injected successfully into the subretinal space in three of six rabbit eyes and in two of two pig eyes. The mean duration required for the drainage of subretinal fluid with the SR-AID was 127 seconds. There was no incidence of significant subretinal hemorrhage or retinal perforation in the animal experiments and in human cases. CONCLUSION: Our case series suggests that the SR-AID provides an efficient and safe means of access to the subretinal space.     

Tissue plasminogen activator treatment of experimental subretinal hemorrhage

Previous investigators have suggested that subretinal blood damages the retina in part because of its solid fibrin meshwork. The role of fibrinolysis in facilitating the clearance of subretinal hemorrhage and preventing degeneration of the overlying retina was studied. Autologous whole blood (0.1 ml) was injected into the subretinal space of 20 rabbits. Twenty-four hours later, the animals were randomized to subretinal treatment with 2.5 micrograms of tissue plasminogen activator or a similar volume of physiologic saline. Mean subretinal hemorrhage thickness 3 days after treatment had decreased to 42% of pretreatment thickness in treated eyes and remained unchanged in control eyes (P less than 0.0005). By 7 days mean clot thickness was 9% in treated eyes and 60% in controls (P = 0.005). Light microscopy revealed severe progressive retinal degeneration in both groups. No histologic evidence of retinal toxicity was found in cat retina after subretinal injection of tissue plasminogen activator (50 micrograms/ml). Although treatment with tissue plasminogen activator accelerated the clearance of subretinal hemorrhage, it failed to prevent secondary retinal degeneration in this rabbit model.     

人视网膜下膜中ICAM-1及MMP-2的免疫组织化学研究

目的观察增生性玻璃体视网膜病变的视网膜下膜中粘附分子（intercellular adhesion molecules-1，ICAM-1）及基质金属蛋白酶（matrix metculoproteinase-2，MMP-2）的表达。方法用免疫组织化学法对15例复杂视网膜脱离行玻璃体切割术时剥离的视网膜下膜进行观察。结果ICAM-1和MMP-2分别在10例和8例视网膜下膜中表达，二者同时在7例视网膜下膜中表达。结论视网膜下膜中有ICAM-1和MMP-2的表达，提示二者在增生性玻璃体视网膜病变的发生发展中有一定作用。     

The development of lacquer cracks in pathologic myopia

We examined three patients with pathologic myopia who had mild visual symptoms and subretinal hemorrhages. None had subretinal neovascularization. In all three patients, lacquer crack lesions of the choroid appeared shortly after clearing of the subretinal hemorrhages. The lacquer cracks were always more extensive than the preceding hemorrhages. These findings support the theory that mechanical stretching and rupture of the Bruch's membrane-pigment epithelium-choriocapillaris complex is the cause of these lesions. Fluorescein angiography helped differentiate these subretinal hemorrhages from those caused by subretinal neovascularization.     

The subretinal fluid in retinal detachment

Following retinal detachment, subretinal fluid (SRF) fills the neoformed space. Subsequently subretinal and preretinal strands of proliferative tissue begin to form. We have collected the subretinal fluid withdrawn during retinal detachment surgery. We have studied subretinal fluid cytologically to evaluate the number and the type of cells present in the fluid, and by means of transmission electron microscopy. The first cell type to be present in the fluid represented degenerated aspects of pigmented epithelial cells (PECs). Successively, other cell types appeared in the fluid as nerve cells (rods, cones and glial cells), macrophages and well preserved pigmented epithelial cells.Abbreviations PECs pigmented epithelial cells - SRF subretinal fluid     

视网膜下液中cAMP,cGMP水平与孔源性视网膜脱离眼内液动态

分别采用蛋白结合法、放射免疫法测定22例孔源性视网膜脱离患者的视网膜下液、外周血中cAMP、cGMP的含量。发现视网膜下液中,cAMP含量高于血浆;cGMP含量低于血浆。提示cAMP含量升高、cGMP含量降低可能抑制了视网膜色素层对视网膜下液的吸收。在行视网膜脱离手术封闭裂孔同时辅以cAMP拮抗剂,是否有利于视网膜下液的吸收,尚需进一步研究。     

Subretinal neovascularization after focal argon laser for diabetic macular edema

The authors reviewed four cases of iatrogenic subretinal neovascularization after focal argon green photocoagulation for clinically significant diabetic macular edema. An inappropriate combination of small spot size with a high-power setting is the common feature in each case of iatrogenic subretinal neovascularization. Close follow-up with fluorescein angiography is used to identify iatrogenic subretinal neovascularization at an early, treatable stage. All four patients responded favorably to laser photocoagulation of the subretinal neovascular membrane.     

Bilateral juxtapapillary subretinal neovascularization associated with pseudotumor cerebri

A 32-year-old obese woman with hypertension and a three-year history of pseudotumor cerebri developed bilateral juxtapapillary subretinal neovascular membranes. To our knowledge, this is the first reported case of bilateral subretinal neovascular membranes complicating the course of this disease. The subretinal neovascular membrane in the left eye spontaneously involuted, but because the membrane in the right eye threatened the foveola, the patient underwent argon-laser photocoagulation. The subretinal fluid and hemorrhage progressively resolved, the membrane was replaced by fibrous tissue, and visual acuity improved. The pathogenesis of the subretinal neovascular membranes was presumably secondary to pressure deformity of the border of Bruch's membrane at the optic disk, creating a discontinuity of normal anatomic apposition of the chorioretinal layers. This anatomic dehiscence, coupled with hypoxia created by axonal tissue swelling and resultant impaired vascular perfusion of the tissues, led to the development of subretinal neovascular membranes.     

Peripapillary subretinal neovascularization in sarcoidosis: remission and exacerbation during oral corticosteroid therapy

BACKGROUND: In sarcoidosis, peripapillary subretinal neovascularization is rare. The role of corticosteroid therapy for subretinal neovascularization is controversial. CASE: A 38-year-old female patient weighing 38 kg with histologically diagnosed sarcoidosis presented with peripapillary subretinal neovascularization, retinal phlebitis, a hyperemic disc, and snowball vitreous opacities in the left eye. OBSERVATION: Oral betamethasone therapy at an initial dose of 3 mg/day reduced the size of subretinal neovascular membrane, and the membrane became fibrous. Despite the total initial 140 mg of betamethasone given over 2.5 months and the additional total 700 mg of prednisolone given over the next 2 months, the subretinal neovascularization recurred. Six months after the first recurrence, a second recurrence developed during the tapering-off period of oral corticosteroid therapy. At the second recurrence, the oral corticosteroid therapy was ineffective in reducing the size of the neovascular membrane. CONCLUSION: In our patient, oral corticosteroids temporarily suppressed peripapillary subretinal neovascularization but failed to prevent extension of neovascular membrane to the fovea because of recurrent sarcoidosis. Over time, oral corticosteroids appear to lose their effectiveness for treating repeated recurrence of peripapillary subretinal neovascularization associated with sarcoidosis.     

Tissue plasminogen activator thrombolysis during surgical evacuation of experimental subretinal hemorrhage.

To assess the role for intraoperative thrombolysis during surgical evacuation of massive subretinal hemorrhage, the authors studied the ability of tissue plasminogen activator (tPA) to facilitate removal of an experimental subretinal blood clot through a small drainage retinotomy. In rabbit eyes, a single subretinal injection of tissue plasminogen activator in concentrations of up to 250 micrograms/ml failed to produce significant (greater than 50%) clot dissolution during a 3-hour period. However, repetitive subretinal lavage and aspiration with tPA (50 micrograms/ml) resulted in progressive intraoperative clot dissolution in rabbits and allowed complete evacuation of blood through a small drainage retinotomy in 6 (100%) of 6 cat eyes. Repetitive vigorous subretinal irrigation with saline solution had no discernible effect on clot size in rabbit eyes. Histopathologic examination of cat eyes following tPA-assisted surgical evacuation of subretinal blood showed preservation of the outer retina in 2 eyes and severe atrophy of the outer retina in 4 eyes.     

Binocular vertical diplopia due to subretinal neovascular membrane

Diplopia is an uncommon finding in patients with subretinal neovascular membranes. We present two patients with binocular diplopia secondary to subretinal neovascular membranes and the foveal displacement syndrome. Subjective diplopia was not improved by prism therapy in either case. In one patient, diplopia was transiently relieved by removal of the choroidal neovascular membrane, but a subsequent subretinal hemorrhage resulted in severe visual loss. In the second patient, diplopia developed following laser therapy for a subretinal neovascular membrane. It is presumed that misalignment of the foveomacular receptor elements between the two eyes produced a central-peripheral fusional mechanism rivalry resulting in binocular diplopia. Ophthalmologists should be aware that a subretinal neovascular membrane may cause binocular diplopia and may mimic neuromuscular strabismus.