Preoperative vitreous hemorrhage associated with rhegmatogenous retinal detachment: a risk factor for postoperative proliferative vitreoretinopathy?

Background: We conducted a prospective clinical study to elucidate the role of preoperative vitreous hemorrhage in the development of postoperative proliferative vitreoretinopathy (PVR) in primary rhegmatogenous retinal detachment. Materials and methods: We prospectively evaluated 409 eyes of 390 patients affected by primary rhegmatogenous retinal detachment referred before any failed attempt to reattach the retina. Single and multiple logistic regression analysis were used to test 14 categories of variables. Results: Postoperative PVR occurred in 48 (11.7% of 409 eyes). Postoperative PVR developed in 41 (11.8%) of the 347 eyes with no preoperative vitreous hemorrhage, and 7 (11.3%) of the 62 eyes with preoperative vitreous hemorrhage (P=0.90). The results of multiple logistic regression analysis showed that only four variables were significant factors which had independently and jointly an effect on the risk of postoperative PVR: (1) 90° or greater circumferential extent of the retinal tears; (2) preoperative PVR grade B; (3) preoperative PVR grade C-D; and (4) the use of cyrotreatment as the method of retinopexy. Conclusion: With the surgical techniques currently used, mild preoperative vitreous hemorrhage is not an independent risk factor for postoperative PVR in primary rhegmatogenous retinal detachment. The role of moderate and severe vitreous hemorrhage remains to be fully evaluated in a larger series of eyes.     

Evidence of chronic inflammation in retina excised after relaxing retinotomy for anterior proliferative vitreoretinopathy

Background: Epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR) frequently express molecules associated with chronic inflammation. To investigate the extent to which inflammation may compromise the detached retina, we determined the expression of inflammatory molecules in anterior retina removed after relaxing retinotomy for retinal detachment complicated by anterior PVR. Methods: Surgical retinal specimens were studied immunohistochemically for the distribution of the vascular cell adhesion molecules VCAM, E-selectin, P-selectin, ICAM and PECAM and for the presence of the cytokine TNF and of T lymphocytes (CD3-positive cells), macrophages (CD68-positive cells) and HLA-DR molecules. The findings were compared with those in control cadaveric retina. Results: Aberrant expresion of ICAM-1 was observed in four of nine retinal specimens from eyes with PVR, whereas its expression in control retinas was confined to the external limiting membrane and ganglion cell layers. PECAM was observed in seven of nine surgical retinal specimens and in four of five controls. E-selectin and P-selectin were expressed within the luminal aspects of four of nine retinal specimens from eyes with PVR, and VCAM was present in three of nine surgical specimens investigated. All cadaveric control retinas were negative for E-selectin and VCAM, whilst one was positive for P-selectin. Staining for TNF was observed within luminal aspects and walls of retinal vessels from eight of nine surgical specimens, but was not seen in any of the cadaveric controls. T lymphocytes and cells expressing the macrophage marker CD68 were identified in two and seven of nine diseased retinas respectively, but not in any of the controls. Cells staining for HLA-DR were observed in eight of nine surgical retinal specimens and in three of five controls. Conclusion: The present findings indicate that retina from eyes with advanced PVR may itself be subject to inflammatory changes, and indicate that the PVR process is not limited to retinal membranes, but involves a more widespread distribution of inflammation than is generally appreciated.     

Cryopexy in primary rhegmatogenous retinal detachment: a risk factor for postoperative proliferative vitreoretinopathy?

Purpose: To evaluate the role of cryopexy in the stimulation of postoperative proliferative vitreoretinopathy (PVR) in primary rhegmatogenous retinal detachment. Materials and methods: A series of 595 eyes of 554 patients with primary rhegmatogenous retinal detachment, referred before any failed surgery, were prospectively evaluated. Univariate and multivariate statistical analyses of the data were conducted. Results: The incidence of postoperative PVR in relation to the methods used for retinopexy was dependent on the types and anatomy of retinal breaks associated with retinal detachment. The incidence of postoperative PVR was nil in retinal detachments due to atrophic holes in lattice, oral dialyses, and macular holes, regardless of the retinopexy methods. Postoperative PVR occurred solely in retinal detachments due to horse-shoe tears (incidence 4.42%), paravascular tears of the postequatorial region (18.18%), and giant tears (24.6%) (P<0.00001). The incidence of postoperative PVR was 0.5% in eyes with horseshoe tears with mobile posterior edges vs 9.72% in eyes with horseshoe tears with curled posterior edges, regardless of the retinopexy methods (P<0.00001). In retinal detachments due to horseshoe tears with mobile posterior edges the incidence of postoperative PVR (0.5%) was not influenced by the retinopexy methods. In contrast, in retinal detachments due to horseshoe tears with curled posterior edges the incidence of postoperative PVR was higher in eyes managed with cryopexy (14.77%) than in eyes managed with laser retinopexy (1.78%) (P<0.02). In retinal detachments due to giant tears the incidence of postoperative PVR was not statistically significantly greater in eyes managed with cryopexy (33.3%) than in eyes managed with laser retinopexy (15.6%). In tears 180° and over in size, however, the incidence of postoperative PVR was significantly higher in eyes managed with cryopexy (9/11 eyes) than in eyes managed with laser retinopexy (5/17 eyes) (P=0.006). Conclusions: Cryopexy is not a stimulating factor for postoperative PVR in primary rhegmatogenous retinal detachments due to atrophic holes in lattice, oral dialyses, macular holes, or horseshoe tears with mobile posterior edges. In contrast, cryopexy probably is a stimulating factor for postoperative PVR in retinal detachments due to horse-shoe tears with curled posterior edges or to retinal tears 180° and over.     

Vitrectomy for traction macular detachment in diabetic retinopathy

Background: A small number of eyes with proliferative diabetic retinopathy develop massive central fibrovascular membranes characterized by vitreoretinal tractions along the arcades and optic disk and retinal traction lines extending through the macula. The aim of our study was first to present the results of vitrectomy for removal of these central membranes and second to determine the correlation between preoperative parameters and postoperative visual outcome. Subjects and methods: We treated 28 eyes with severe central fibrovascular diabetic membranes by a modified bimanual en bloc excision technique during vitrectomy. Preoperative examination included general status, visual acuity, slit-lamp investigation, binocular funduscopy, ultrasound investigation and visual evoked potentials (VEP). Further, we analyzed intraoperative complications and postoperative anatomic and functional outcomes. Results: The retinas of 27 eyes with central traction retinal detachments were reattached by surgery. With a minimum of 6 months' follow-up, the macula remained attached in 24 eyes, while the retinas were completely attached in 22 eyes. Preoperative visual acuity was defective light perception to 0.1; an increase in visual acuity to maximal 0.1 was seen in 50% of the patients postoperatively. Preoperative visual acuity of light perception was associated with no functional improvement. Preoperative ultrasound investigation gave information about the real anatomic situation of the retina, especially if funduscopy was not possible. The other preoperative parameters could not predict correctly the functional outcome of vitrectomy in diabetics with severe central fibrovascular membranes because of the damage of the optic nerve and the retina. Conclusions: The high rate of anatomical rettachment after vitrectomy in diabetic eyes with severe central fibrovascular membranes is associated with a slight improvement of function; only preoperative visual acuity of hand motions or better was associated with an improvement of function.     

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.     

The ultrastructure of parapapillary chorioretinal atrophy in eyes with secondary angle closure glaucoma

Background: The present study was performed to investigate the ultrastructure of deep retinal layers and choroid corresponding to the parapapillary chorioretinal atrophy in eyes with secondary angle-closure glaucoma. Methods: The glaucomatous eyes included two eyes enucleated due to iris ring melanoma with high intraocular pressure and one eye with neovascular glaucoma enucleated due to ocular pain. The control eyes included one eye enucleated due to choroidal malignant melanoma with normal intraocular pressure and one eye enucleated during surgery for supramandibular carcinoma. These eyes were studied with light and electron microscopy. Results: In the region of parapapillary chorioretinal atrophy of glaucomatous eyes, the retinal pigment epithelial cells showed degenerative changes, such as loss of basal in foldings and microvilli, degenerated mitochondria, vacuolar degeneration and irregular distribution of melanin granules. The photoreceptors were decreased in number in this area of glaucomatous eyes. The lumen of the choriocapillary vessels adjacent to the optic nerve was collapsed. Conclusion: These results elucidate the fine structures of deep retina and choroid in the region of parapapillary chorioretinal atrophy of glaucomatous eyes, and suggest that the reduced choroidal perfusion might be the pathogenetic mechanism of glaucomatous parapapillary chorioretinal atrophy.     

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.     

Immunohistochemical evaluation of the integrity of the blood-aqueous barrier in normal and rubeotic human eyes

Background: The integrity of the blood-aqueous barrier (BAB) was analyzed using an immunohistochemical technique for the demonstration of albumin. Methods: Paraffin sections of 36 normal eyes obtained from eye banks or at autopsy (mean age 62.8 ± 15.2 years) and 46 eyes with marked iris neovascularization (mean age 54.6 ± 25.3 years) were formalin-fixed and examined using rabbit anti-human albumin. Results: In normal eyes, albumin staining was found in the iris stroma inside and outside the iris vessels but was not detected across the anterior iris border; albumin was present in the anterior chamber in one eye, but not internal to the nonpigmented ciliary epithelium. In rubeotic eyes, albumin staining extended along the anteri or iris in all 46 cases; albumin was demonstrated in the anterior chamber in 31 eyes and along to the nonpigmented ciliary epithelium in 13 eyes. Differences between normal and rubeotic eyes were significant for intensity of albumin staining in the iris stroma and for presence of albumin along the anterior iris, within the anterior chamber, and along the ciliary epithelium (P < 0.001, ² test). Conclusion: Our findings indicate that the BAB may be less resistant to leakage in the iris stroma than at the ciliary epithelium. BAB breakdown in rubeotic eyes occurred mainly in the iris; the ciliary epithelium was much less involved. Immunohistochemical staining for albumin appears to be useful for evaluating the integrity of the BAB in human pathologic specimens.     

The effect of chemical stability and purification of perfluorocarbon liquids in experimental extended-term vitreous substitution

Background: To determine the importance of chemical stability and purification of perfluorocarbon liquids (PFCLs) in experimental retinal tolerance, we tested four different substances as long-term vitreous tamponade: purified and nonpurified perfluorodecalin (PFD) and perfluoro-octylbromide (PFOB) Method: After mechanical vitrectomy we replaced the vitreous of 65 rabbit eyes. Five groups were formed; four of them received the four PFCLs, while one served as control and received Ringer solution. The eyes were observed clinically every week and examined histologically after 1, 2, 4 and 8 weeks Results: After 1 week we observed foam cells and intraretinal macrophages in all eyes with PFCLs. Purified PFD caused retinal lesions in the photoreceptor, ganglion cell and outer nuclear layers after only 2 weeks in the lower part of the eyes. In eyes filled with purified PFOB we observed more pronounced damage of the same nature. Unpurified substances caused severe inflammation and retinal detachment Conclusion: Our study demonstrates that purification and chemical stability are important factors in retinal tolerance of PFCLs for vitreous replacement. Although purified PFD was tolerated by the rabbit eyes for 1 week, we cannot recommend this substance for short-term clinical use as a vitreous substitute.     

Optic disc morphology in diabetes mellitus

Background: Diabetes mellitus is a systemic disease affecting multiple tissues throughout the body. This study was performed to evaluate intravitally the diabetic changes of the optic disc Methods: Color photographs of 115 eyes with varying severity of diabetic retinopathy and of 29 normal eyes were morphometrically examined Results: We found that the size and shape of the optic disc, the neuroretinal rim and the parapapillary atrophy did not differ significantly between the diabetic eyes and the normal eyes. These variables were independent of the degree of diabetic retinopathy. There was a tendency toward decreased visibility of the retinal nerve fiber layer and increased optic disc pallor in the diabetic eyes Conclusion: The results indicate that the area and form of the optic disc, the neuroretinal rim and parapapillary atrophy are not altered by diabetes mellitus. This is important for the diagnosis of glaucoma in diabetic patients, since glaucoma leads to a decrease of rim area and an enlargement of parapapillary atrophy. The reduced visibility of the retinal nerve fiber layer, the increased optic disc pallor and the unchanged size of the neuroretinal rim and parapapillary atrophy suggest that diabetes mellitus may be associated with nonglaucomatous optic nerve atrophy.     

β-Galactosidase transgene expression in transplanted rabbit retinal pigment epithelial cells in vivo

Background: Intraocular transplantation of genetically modified cells that release a particular substance could have a major impact on the treatment of various ocular diseases. We studied the expression of the reporter gene -galactosidase (lacZ) in transplanted retinal pigment epithelial (RPE) cells in vivo Methods: RPE cells from pigmented rabbits were transduced with the -galactosidase gene in a retroviral vector. Cells were then assayed for gene expression and transplanted subretinally into the eyes of New Zealand White rabbits. RPE cells that were transduced with a similar vector without the -galactosidase gene were used as controls. Rabbits were killed on days 1, 7, and 21 and the eyes processed for transmission electron microscopy Results: Neomycin-resistant rabbit RPE cells that showed -galactosidase activity were generated within 2–5 weeks. After transplantation, viable RPE cells that expressed the transgene and that phagocytosed rod outer segments were observed on days 1, 7, and 21 Conclusions: The results show that generation of genetically modified RPE cells is feasible and that the transplanted cells remain viable and continue to express the transgene in the subretinal space of the host animal for at least 21 days. Transplantation of such genetically modified RPE cells could provide a new tool for studying retinal diseases and, potentially, for correcting metabolic abnormalities in retinal degenerations and dystrophies.     

Toward robot-assisted vascular microsurgery in the retina

Background: Experimental protocol in our laboratory routinely requires the precise placement of instruments at, or near, the retina. Although manipulators for placing an instrument within the eye presently exist, none of the designs were satisfactory due to limitations on size, accuracy and operability. To overcome these limitations, we have developed a novel six degree of freedom manipulator designed specifically for retinal microsurgery. Methods: The manipulator is parallel in structure and provides submicrometer positioning of an instrument within the constrained environment of the eye. The position of an instrument attached to the manipulator is commanded by the operator using a hand-held trackball. A computer controller interprets the trackball input and moves the manipulator in an intuitive manner according to mathematically constrained modes of operation. Results: Over 50 retinal vessels in the live, anesthetized cat have been successfully cannulated for pressure measurement and drug injection using the described manipulator and micropuncture techniques. The targeted vessels ranged in internal diameter from 20 to 130 pm. Conclusion: This device has applications in microsurgery where tremor and fatigue limit the performance of an unaided hand and where mechanically constrained manipulators are inappropriate due to size and operative constraints.     

Anterior chamber inflammation after transconjunctival cryosurgery

Background: Inflammation caused by transconjunctival cryotherapy for prophylactic retinal detachment surgery was measured in various conditions. Methods: Thirty-four eyes of 28 patients with peripheral retinal lesions predisposing to retinal detachment were studied by laser flare cell meter before and after treatment. Results: The mean flare value for 34 eyes was 4.06 ± 1.45 photon counts/ms before surgery and 5.72 ± 2.52 pc/ms after surgery (p < 0.05). Flare value was elevated at 1, 2, and 3 weeks after treatment, peaking at 2 weeks (p < 0.05), and normal again at 4 weeks. There were no significant differences in flare increase between eyes with and without retinal breaks, eyes with and without limited retinal detachment, eyes with myopia more and less than – 8.0 D, and eyes with a treatment area limited to one quadrant and extending over more than one quadrant. Conclusion: Transconjunctival cryosurgery caused mild inflammation in the anterior chamber of the eye for 3 weeks. The inflammation was not affected by the presence of retinal break or limited retinal detachment, the degree of myopia, or the extent of the treatment area.     

HLA antigens in a Japanese family with Behçet's disease

Background: Familial Behçet's disease is rare. Methods: HLA antigens in a Japanese family with Behçet's disease were examined. Results: The affected patients had HLA B51, and unaffected family members also had the same antigen. Conclusion: It is likely that not only HLA B51 but also other factors may be involved in the pathogenesis of Behçet's disease in Japanese patients.     

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.     

Familial exudative vitreoretinopathy: surgical intervention and visual acuity outcomes

Background: Familial exudative vitreoretinopathy (FEVR) is a hereditary condition that may lead to vitreous hemorrhage and traction retinal detachment necessitating surgical intervention. In this paper we review the results of surgery on seven such patients (eight eyes). Methods: Seven patients (eight eyes) were followed up after surgery that had been performed because of vitreous hemorrhage and/or traction retinal detachment due to FEVR, in an effort to evaluate outcomes. Parameters that were noted were the current age, gender, age at the time of first surgery, length of follow-up and postoperative retinal status and visual acuity. Results: Seven patients (eight eyes) ranging in age from 6 months to 44 years with a mean of 24.7 and a median of 26 years were followed. There were three females and four males. The lowest age at which surgery was first performed was 6 months and the highest was 28 years, with a mean of 14.7 and a median of 17 years. Six of the 8 eyes were reattached following surgery, although some required multiple procedures. Conclusion: Vitreoretinal surgery may be of benefit in helping to preserve some degree of vision in eyes of patients with FEVR who develop vitreous hemorrhage and/or retinal detachment.Presented at the combined meeting of the Club Jules Gonin and the Retina Society, 3 September 1996     

Pseudophakic retinal detachment: anatomic and visual results

Background: Our purpose was to report the anatomic and visual results of pseudophakic retinal detachment surgery in a large series of consecutive cases and to analyze the risk factors for anatomic and functional failure. Methods: This retrospective study covered 290 primary cases of idiopathic rhegmatogenous retinal detachment operated on by the same surgeon during an 8-year period. Data relating to 26 pre-, per-, and postoperative variables were studied. For the statistical analyses we used both Chi-square and stepwise logistic regression tests. Results: Vitreous loss occurred in 56 cases (19.3%), and the retina detached more than 2 years after lens extraction in 108 cases (37.2%). Breaks could be identified in 249 cases (85.8%), and the macula was involved in 235 (81%). The overall reattachment rate was 85.2% (247/290), and a postoperative visual acuity of 0.5 D or more was attained in 49.6% of cases (144/290). We found no differenc between phakoemulsification, extracapsular, intracapsular techniques or between anterior chamber, posterior chamber, iris-fixated lenses as regards anatomic and functional outcomes. Proliferative vitreoretinopathy (PVR) and photoreceptor dysfunction were the main causes of anatomic and functional failure respectively. We identified extensive detachment, preoperative choroidal detachment, intraoperative hemorrhage and surgery for PVR as predictors of anatomic failure, while preoperative inflammation, preoperative PVR of grade B or worse, and surgery for PVR were predictors of functional failure. Conlusion: In this series, anatomic and visual results of reattachment surgery were much more affected by detachment features and by PVR than by the techniques and complications of cataract surgery.     

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.     

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.     

The retinal depression sign in diabetic retinopathy

Background: The retinal depression sign, an abnormal light reflex due to ischemia-induced focal inner retinal atrophy, was initially described in patients with sickle cell retinopathy. We undertook this study to characterize the finding in diabetic retinopathy. Methods: The fundus photographs of 97 consecutive patients with diabetic retinopathy seen in the Penn State University Ophthalmology Department were reviewed. We recorded age, sex, type of retinopathy, visual acuity and photographic details, including the presence or absence of the retinal depression halo. Results: The retinal depression sign was present in 9 of 22 patients age 45 years or under, versus 1 of 75 patients age 46 or older (P<0.0001, two-tailed Fisher's exact test). The presence or absence of retinal depression sign did not predict the type of retinopathy in a given patient. Eleven (70%) of the affected eyes had visual acuity 20/40. Conclusion: The retinal depression sign is common in younger patients with diabetes and should be distinguished from other macular lesions associated with diabetic retinopathy.