Unusual retinal pigment epitheliopathy and choroidopathy in carcinomatosis: A rare case of cancer-associated retinopathy

Background: Cancer-associated retinopathy is a syndrome causing ocular symptoms. It is a rare entity and only a few cases have been reported. Methods: A 67-year-old woman with small-cell endometrial carcinoma suffering from deterioration of visual acuity is presented. Results: The patient presented with extensive mottled changes of the retinal pigment epithelium, accompanied by diffuse subretinal fluid in the posterior pole and exudative retinal detachments inferior in both eyes. Conclusion: This patient suffered from a rare variety of cancer-associated retinopathy.     

Epidemiologic characteristics of rhegmatogenous retinal detachment in Kumamoto,Japan

Background: The epidemiology of rhegmatogenous retinal detachment in Asians is not well known. We studied the epidemiologic characteristics of rhegmatogenous retinal detachment in Kumamoto, Japan. Methods: The study was based on a retrospective chart review of hospital patients who were treated for primary rhegmatogenous retinal detachment in 1990. The data were collected from seven hospitals in the Kumamoto area. Results: From a population of 1 840000, 192 residents developed retinal detachment. The annual incidence was therefore 10.4 per 100000 population (9.6 for males, 11.2 for females). The incidences of three types of detachment — nontraumatic phakic, aphakic, and blunt trauma — were 9.8, 0.5, and 0.2 per 100000 population, respectively. In 109 of 180 patients (60.6%) with nontraumatic phakic detachment, retinal breaks were associated with lattice degeneration. In females, 14 of 106 nontraumatic phakic cases (13.2%) were secondary to macular holes. Conclusion: Compared with previously published studies from other countries, the incidence of detachments associated with lattice degeneration and macular hole was higher, while the incidences of aphakic detachment and detachment due to blunt trauma were lower in Japan. Racial factors and living habits may affect the development of retinal detachment.     

Expression of mRNA coding for TNFα, IL-1β and IL-6 by cells infiltrating retinal membranes

Background: Cellular mechanisms of inflammation are thought to be involved in the pathogenesis of proliferative vitreoretinopathy, and cytokines, which are products of cell activation, are known to play an important role in the development and maintainance of inflammatory reactions. It was the aim of this work to investigate the presence of cells expressing cytokine mRNA within retinal membranes. Methods The presence of mRNA coding for the cytokines interleukin 1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor (TNF) was investigated in 19 epiretinal membranes obtained from eyes undergoing vitrectomy for the treatment of retinal detachment complicated by proliferative vitreoretinopathy. Results Cells expressing mRNA for IL-1 were observed in 7 membranes, cells positive for IL-6 mRNA were seen in 12 membranes, and cells exhibiting mRNA for TNF were present in 9 specimens. Only three membranes contained cells expressing mRNA for all the cytokines investigated. Four membranes possessed positive cells for IL-6 and TNF, two contained cells expressing mRNA for IL-6 and IL-1, and two others exhibited cells expressing mRNA for TNF and IL-1. Five membranes contained IL-6 mRNA-positive cells only, whilst two exhibited cells expressing mRNA for IL-1, or TNF only. Conclusion The present findings indicate that cellular activation may occur during the development of PVR, and suggest that these cytokines may be locally produced by cells infiltrating epiretinal membranes. The presence of IL-1, IL-6 and TNF mRNA-positive cells within retinal membranes provides further evidence of a pathogenic role of these cytokines in proliferative vitreoretinopathy.     

Blood-retina barrier in acute retinal branch vein occlusion

Background: Extensive clinical studies on retinal branch vein occlusion have not yet been able to clarify its pathogenesis. A study designed to look at the associated blood-retina barrier changes may contribute to a better understanding of the different forms of evolution of this pathology. Methods: A prospective study was done in seven patients with recent large temporal branch vein occlusion. Vitreous fluorophotometry, fluorescein angiography and retinal colour photography were performed within the 1st week after the onset of symptoms, 1 week later, and at 12 and 24 weeks. Results: A more marked blood-retina barrier breakdown was found at 1, 2, 12 and 24 weeks in the eyes that later developed extensive capillary non-perfusion. Conclusions: Our results suggest that the breakdown of the blood-retina barrier may play an important role in the subsequent development of retinal nonperfusion in eyes with large branch vein occlusion. We postulate that the eyes that will present later extensive capillary nonperfusion develop, from the initial stages of the disease, a progressive ischaemic capillaropathy characterized by blood-retina barrier breakdown. Retinal pigment epithelium degeneration and arterial lumen narrowing, secondary to the vein obstruction, may help to increase and perpetuate the blood-retina barrier breakdown during the first 6 months after the occlusion.     

Pars plana vitrectomy for retinal detachment due to internal posterior ophthalmomyiasis after cataract extraction

Background: The authors report a case of posterior internal ophthalmomyiasis causing vitreous haemorrhage and retinal detachment after uncomplicated cataract extration. Case report: The patient suffered an abrupt vitreous haemorrhage 9 days after ECCE and posterior chamber IOL implantation. After 2 months the haemorrhage did not clear up and a retinal detachment arose. The patient underwent encircling scleral buckle, pars plana vitrectomy and fluid-gas exchange. In course of intervention the surgeon removed from the vitreous chamber a 14-mm-long round worm subsequently identified as a dipterous larva of the Sarcophagidae family. Discussion: The patient showed no sign of subretinal tracking or retinal breaks or holes. The sclerocorneal surgical wound seems the most likely site of entrance of the parasite, and this would then be the first reported case of myiasis with no RPE tracking.     

Retinopathy in diabetic hypertensive monkeys: a pathologic study

Background: No satisfactory primate model of diabetic retinopathy has been produced. The clinical picture of microangiopathic retinopathy in diabetic hypertensive monkeys has been previously reported. The present study describes the pathologic findings of these animals. Methods: Eleven eyes of six monkeys (five rhesus, one cynomolgus) were studied. Diabetes mellitus was either spontaneous or induced by streptozocin; mild arterial hypertension was either spontaneous or induced by fludrocortisone acetate. In two monkeys, the horseradish peroxidase tracer technique was employed. Trypsin flat preparations of the nasal retinal vasculature were prepared. The material was studied by light and electron microscopy. Results: We divided the development of the microangiopathic retinopathy into three stages. In the early stage, background retinopathy was characterized by microvascular abnormalities and capillary dropout. Massive vascular leakage, intraretinal exudates and hemorrhage, cystoid degeneration, and cotton-wool spots were features of an exudative retinopathy in the second stage. In the final stage, chronic ischemic retinopathy was characterized by vascular occlusions and areas of retinal atrophy. Conclusion: Microangiopathic retinopathy in diabetic monkeys with mild hypertension presented many features of human diabetic and hypertensive retinopathy, except vitreous neovascularization.     

Scanning laser ophthalmoscope imaging of fluorescein-labelled blood cells

Purpose: To demonstrate the feasibility of a technique for the visualization by scanning laser ophthalmoscope (SLO) of fluores cein-labelled autologous leukocytes and platelets in retinal vessels. Method: Individual blood samples from rats and rabbits were centrifuged to isolate platelets and leukocytes, then passively labelled with fluorescein and reinjected into the same animal. An SLO was used to visualize and record cell displacement in the retinal circulation. Labelled platelets were analysed by flow cytometry. Results: By SLO, platelets appeared as a heterogeneous particle flow, and individual leukocytes appearing as brighter spots could easily be traced. Flow cytometry showed that after labelling platelets were well individualized and their size was slightly increased. Conclusion: Circulating blood cells can be visualized in retinal vessels by a simple method consisting of passive labelling of autologous platelets and leukocytes by fluorescein. No platelet toxicity was detected. This method could be applied to the study of blood cell movement in human retinal vascular diseases.Proprietary interest category: N     

How often do patients need visual field tests?

Background: This study was undertaken to determine whether the interval between visual field tests affects the ability to detect progres sive glaucomatous field loss. Methods: One hundred and nineteen retinal locations which were deteriorating significantly by 1 dB/year (untreated normal tension glaucoma patients: 6 eyes) were studied. Analysis was repeated using thinned visual field tests: one test per year instead of the complete three per year over a period of 4 years. Results: The thinned tests identified only 45.4% of the deteriorating points over the 4-year period. Furthermore, there was a mean delay of 1.10 years in detection (P<0.01). Conclusions: Less frequent visual field testing detects fewer progressing locations and detects them later.Presented in part at the Association for Research in Vision and Ophthalmology Annual Meeting, May 1995 and at the American Academy of Ophthalmology Meeting, October 1995.The authors have no proprietary interest in any of the materials used in this study.     

A comparison of colour Doppler imaging of orbital vessels and other methods of blood flow assessment

Background: Comparison of the haemodynamic measurements obtained by colour Doppler imaging and other methods of ocular blood flow measurements was desired. Methods: The blood velocity findings from colour Doppler imaging of patients with central retinal vein occlusion were compared to the results of fluorescein video-angiography, continuous tonography and ophthalmodynamometry. Results: Patients with low or undetectable blood velocities in the central retinal vein had longer retinal dye transit times on fluorescein video-angiography. Tonography showed a positive correlation with the velocities in the ophthalmic artery, but ophthalmo-dynamometry showed a negative correlation with these velocities. Conclusion: The relationships between the blood velocities in orbital vessels and other blood flow measurements emphasise that there is a complex interaction of the blood flow parameters. Care must therefore be taken when interpreting the results of studies.     

Tolerance of human fetal retinal pigment epithelium xenografts in monkey retina

Background: RPE transplantation offers the possibility of treating certain forms of retinal degeneration. Understanding how to optimize the surgical technique for performing RPE transplantation, especially in primates, is therefore of considerable interest. Methods: Fifteen patch RPE transplants were performed in six monkeys. The transplant sites were examined at follow-up by ophthalmoscopy, biomicroscopy, fluorescein angiography and histology. Foveal and peripheral retinal transplants were compared. Results: Human fetal RPE xenografts can survive without rejection for at least 6 months after transplantation in monkey retina. Such grafts form a basal lamina and make intimate contacts with the outer segments of the host. Both rods and cones retain a normal appearance when in contact with unrejected transplants. Rejection occurred in only 30% (3/10) of the peripheral but in 60% (3/5) of the foveal transplants. Conclusions: Cultured human fetal RPE patch transplants can survive and maintain local photoreceptor integrity for relatively long periods of time in monkey subretinal space without immunosuppression. Rejection, when it occurs, is more frequent near the fovea.     

Effects of norfloxacin on the retina in rabbits

Background: Fluoroquinolones have a strong affinity with melanin, and their ocular effects have been reevaluated. Norfloxacin, one of the fluoroquinolones, has broad-spectrum activity against aerobic gram-positive and gram-negative bacteria. We examined the retinal toxicity and intraocular pharmacokinetics of intravitreal norfloxacin in rabbits. Methods: Twenty-three albino and 23 pigmented rabbits were divided into three groups to evaluate retinal toxicity and two groups to investigate the intraocular pharmacokinetics. Each of these five groups was further divided into two subgroups (albino rabbits and pigmented rabbits). Results: With 500 Etg norfloxacin, the oscillatory potential of the electroretinogram was transiently and selectively deteriorated in albino and pigmented rabbits, whereas the electroretinogram remained unchanged with 50 g in pigmented rabbits. No changes were observed in the visual evoked potential or on histology of the retina 7 days after an intravitreal injection of 50 or 500 ltg norfloxacin. The electroretinogram and the retinal histology became abnormal 7 days after four intravitreal injections of 500 g norfloxacin at 7-day intervals. As regards the intraocular pharmacokinetics after an intravitreal injection, the norfloxacin concentration in the chorioretina was as high as that in the vitreous 3 h after injection and was much higher than that in the vitreous 7 days after injection. Similar results were obtained after multiple injections. Conclusion: These results indicate a high concentration of norfloxacin in the melanin-containing ocular tissues.     

Fundus pulsation measurements in diabetic retinopathy

Background: There is experimental evidence that retinal blood flow is impaired in patients with diabetes mellitus. Much less attention has been paid to choroidal blood flow. Hence it was the aim of the present study to investigate choroidal blood flow in diabetic retinopathy. Methods: A new noninvasive laser interferometric technique was used to measure fundus pulsations in the macula. The fundus pulsation amplitude, which is the maximum distance change between cornea and retina during the cardiac cycle, is a measure of local pulsatile blood flow. The eyes (n = 214) were divided into four groups according to the modified Airlie House classification: (1) no retinopathy (control group), (2) background retinopathy, (3) moderate to severe preproliferative retinopathy, (4) proliferative retinopathy. In 83 eyes of different groups fundus pulsation measurements were repeated after 1–6 weeks. Results: Fundus pulsation amplitudes were significantly smaller in group 4 than in the control group (P < 0.027). The reproducibility of the measurements was high and did not differ among the study groups. Conclusions: Local fundus pulsations in the macula are reduced in proliferative diabetic retinopathy, which is compatible with previous findings of reduced choroidal blood flow in late stages of the disease. Laser interferometric measurement of fundus pulsations is non-contactile, assures optimal comfort for the patient and could be used for the long-term observation of patients with diabetes mellitus.     

Pressure sore in a patient who underwent repair of a retinal tear with gas injection

Purpose: To demonstrate a pressure sore following strict head positioning in a patient who underwent encircling band, vitrectomy and gas injection. Methods: A male patient was admitted to the hospital with a large posterior horseshoe tear in the inferior temporal retina with severe vitreous traction and retinal detachment. Encircling band, vitrectomy cryotherapy and gas injection was performed. After surgery the patient was instructed to sit in a facedown position. Results: A pressure sore resulted from prolonged immobility of the right elbow due to face-down positioning following encircling band, vitrectomy and gas injection. Conclusion: A patient injection. Conclusion: A patient may rarely have compulsive personality traits that result in extreme compliance to the physician's recommendations; therefore, general instructions given for head positioning should include permission for a change in position when required, at least for brief periods of time.     

Influence of oxygen free radicals and free radical scavengers on the growth behaviour and oxidative tissue damage of bovine retinal pigment epithelium cells in vitro

Purpose: This investigation was carried out to ascertain whether oxygen free radicals can influence the growth behaviour and consecutive lipid peroxidation of retinal pigment epithelium (RPE) cells in vitro and whether scavengers can counteract these effects. Methods: The experimental model was based on calf RPE cells. Hypoxanthine/xanthine oxidase (HX/XO) and superoxide dismutase/catalase (SOD/CAT) served as the radical generating system and scavengers, respectively. The components were tested alone and in combination. Lipid peroxides were determined in culture supernatants by a thiobarbituric acid assay. Results: Concentrations of up to 100 mol/1 of HX alone and 500/1000 U of XO alone, as well as the application of the scavengers without the radical generating system (HX/XO), had no effect. Doserelated reduction of cell growth and increase of lipid peroxidation were found with HX/XO treatment (single dose of 500 and 1000 U/ml 24 h after seeding). After application of 500 or 1000 U/ml of XO, CAT, when given alone (1200 U/ ml), counteracted the effect of the radicals on cell growth and lipid peroxidation; SOD (300 U/ml) had no effect. A combination of SOD and CAT was no better than the effect of CAT alone. Conclusion: The prevention of radical-induced reduction of cell growth and lipid peroxidation by scavengers supports trials of therapy using antioxidants and/or free radical scavengers for various ocular syndromes with RPE involvement.     

Reattachment to a substrate prevents apoptosis of human retinal pigment epithelium

Background: Epithelial cells generally fail to survive in suspension. Harvesting human retinal pigment epithelium (RPE) for transplantation may separate the cells from their extracellular matrix and induce apoptosis. We investigated whether reattachment of RPE to a substrate will prevent apoptosis. Methods: Second-passage human RPE cells were plated onto tissue culture plastic precoated with extracellular matrix, fibronectin or laminin, uncoated tissue culture plastic, untreated plastic and untreated plastic coated with 4% agarose. Reattachment rates were determined for each substrate 24 h after plating. The TUNEL technique was used to determine apoptosis rates in attached cells, unattached cells and the entire cell population. Results: Attachment rates were as follows: ECM-coated tissue culture plastic fibronectin-coated tissue culture plastic laminin-coated tissue culture plastic uncoated tissue culture plastic untreated plastic agarose-coated untreated plastic. Apoptosis rates for the entire cell population increased as the RPE cell attachment rate decreased. The proportion of apoptotic cells in the entire population was inversely related to the percent attached cells (r = -0.95). Conclusion: Reattachment of harvested RPE to a substrate decreased the rate of RPE apoptosisin vitro. RPE cells which are removed from their substrate prior to transplantation must reattach rapidly to a substrate to prevent apoptosis.Presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, May 1996     

Visualization of retinal and choroidal blood flow with fluorescein leukocyte angiography in rabbits

Purpose: To visualize the retinal and choroidal leukocytes in rabbits with a new technique, fluorescein leukocyte angiography using a scanning laser ophthalmoscope. Methods: Blood was withdrawn from an ear vein of a rabbit (New Zealand White), mixed with fluorescein dye in a test tube and centrifuged. The yellow-brown coat layer containing fluorescein-stained leukocytes was collected and injected into the ear vein of the same rabbit while performing fluorescein angiography with a scanning laser ophthalmoscope. The angiographic image displaying circulating fluorescent leukocytes in retinal and choroidal vessels was recorded on a videotape. Results: Fluorescent leukocytes were clearly visible in the retinal arteries, capillaries, veins and choroidal vessels for more than 1 h. Plugging of leukocytes was seen throughout this period of time in choroidal vessels, while plugging was rare in retinal vessels. Conclusions: Fluorescein leukocyte angiography is a new technique which can be used for visualization of the leukocytes in retinal and choroidal vessels non-invasively and in vivo.Presented in part at the 5th International Meeting on Scanning Laser Ophthalmoscopy, Tomography, and Microscope, San Antonio, Texas, 26–28 October 1995; Presented as a video presentation at the 76th meeting of the Korean Association of Ophthalmology (Seoul, 15–16 May 1996     

Isovolemic hemodilution increases retinal tissue oxygen tension

Background: Therapeutic isovolemic hemodilution has been reported to improve blood flow and oxygen delivery. Few reliable measurements have been made, however, showing the effect of hemodilution on tissue oxygen tension. Methods: We measured retinal oxygen tension during experimental isovolemic hemodilution in normal cats. Polarographic oxygen microelectrodes were placed in the vitreous humor within 100–200 m of the retinal surface.Results: Tissue oxygen tension increased initially during isovolemic hemodilution to a maximum approximately 50% above baseline at approximately two thirds of the original hematocrit level. Hemodilution beyond this point to lower hematocrits caused a steady decline in tissue oxygen tension. Cardiac output measured in one cat undergoing isovolemic hemodilution increased as hematocrit was lowered, but the cardiac erythrocyte flux actually decreased steadily.Conclusion: The observed increase in tissue oxygen tension with hemodilution appears to be explained by a lesser reduction in capillary than in systemic hematocrit, coupled with an increased capillary blood flow. The increase in tissue oxygen tension we observed could in part explain the clinically beneficial effects of hemodilution.     

The effect of high-dose methylprednisolone on laser-induced retinal injury in primates: an electron microscopic study

Background: Previously we reported an ameliorative effect of high-dose methylprednisolone in laser injury to monkey retinas. The ultrastructural modification by methylprednisolone has not been examined. Methods: Cynomolgus monkeys were given severe kgrade III) retinal laser burns and treated with an intravenous megadose of methylprednisolone. Pathologic features of the retinal lesions with or without methylprednisolone treatment were evaluated by light and electron microscopy. Results: Ultrastructurally, the treated lesions showed rapid recanalization of choriocapillaris; proliferation of retinal pigment epithelium to replace the necrotic and damaged cells, resulting in rapid re-establishment of blood retinal barrier; mild macrophagic activity; and rapid reformation of the outer limiting membrane by Mueller cells. Conclusion: A high dose of methylprednisolone affected the responses of the choriocapillaris, retinal pigment epithelium, photoreceptor cells and Mueller cells to laser injury, showing an overall beneficial effect. These modifications might be ascribed to methylprednisclone's anti-inflammatory action, protection of the microcirculation and anti-lipid peroxidation effect. Proprietary interest: none     

An immunocytochemical study of isolated human retinal Müller tells in culture

Background: We report a modified method for the isolation and propagation of adult human Müller cells in culture. Methods: The retina of postmortem human eyes was mechanically dissociated and cultured. Using immunocytochemical techniques, these cells were stained with monoclonal antibodies specific for Müller cells, glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase (GS) and keratin. Transmission electron microscopy (TEM) was also performed. Results: The dissociated and cultured cells expressed vimentin and GS, but not GFAP. At least 85% of these cells stained with a Müller tell-specific monoclonal antibody. Using TEM, flat cells containing 13-nm intermediate filaments and glycogen were identified. Conclusion: Human retinal Müller cells tan be isolated and propagated in culture. Purified cell cultures are required for controlled studies of the normal physiology and pathologie responses of Müller cells.     

The use of tissue plasminogen activator in post-traumatic total hyphaema

Background: We wanted to evaluate whether intracameral injection of tissue plasminogen activator (tPA) is useful in managing traumatic hyphaema. Methods: Two eyes with total hyphaema after a severe penetrating injury were treated with a single intracameral injection of 25 g of tPA 5 and 14 days after the injury, respectively. Results: Most of the blood coagulum dissolved within 24 h, and in one of the two eyes the intraocular pressure decreased from 45 to 8 mmHg. The other eye was hypotonic. No re-bleeding or complications related to the use of tPA were noticed. Conclusion: The results in these two cases suggest that tPA is a useful adjunct in managing total hyphaema.