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Optical coherence tomography in the detection of retinal break and management of retinal detachment in morning glory syndrome.

PURPOSE: To determine the efficacy of optical coherence tomography (OCT) in the management of retinal detachment in morning glory syndrome (MGS). DESIGN: Prospective, interventional case series. METHODS: Five eyes of five consecutive MGS patients who developed retinal detachment between August 2000 and June 2004 were enrolled and examined by OCT at presentation of retinal detachment. Four eyes were found to have a slit-like break at the margin of the excavation by careful OCT scanning 360 degrees around the excavation. All four eyes underwent pars plana vitrectomy, gas injection and postoperative laser photocoagulation. Postoperative OCT was performed to confirm the closure of the retinal break and reattachment of the retina. RESULTS: Optical coherence tomography detected a slit-like break at the margin of excavation in four of five patients. The retina reattached in all five eyes over the subsequent 3-50-months (average 28 months) follow-up period. Postoperative OCT showed retinal break closure at the margin of the excavation. In the one eye in which no retinal break could be detected by OCT, the retina was reattached after pars plana vitrectomy and removal of gel-like tissue. CONCLUSIONS: Optical coherence tomography is beneficial in the detection of subtle slit-like breaks at the margin of excavation in retinal detachment in MGS. It provides good guidance in subsequent surgery and is very helpful in confirming the closure of the retinal break.

Adult↗

Retinal detachment and herpesvirus retinitis in patients with AIDS.

BACKGROUND: The prolongation of survival of patients with herpesvirus retinitis and AIDS has been associated with a rise in the incidence of retinal detachment. In such cases, however, retinal reattachment may be difficult to achieve, and postoperative visual acuity may be poor despite anatomically successful surgery. METHODS: In order to examine factors affecting the visual outcome of surgery, a retrospective review of 29 patients with retinal detachment, herpesvirus retinitis, and AIDS was performed. Retinal reattachment surgery (32 procedures) or prophylactic laser demarcation (five procedures) was performed in 28 eyes of 23 patients. RESULTS: The macula was attached in 23/28 (82%) eyes at the last outpatient visit. Best postoperative visual acuity (median 6/18, range 6/6-hand movements) was significantly greater than final postoperative acuity (median counting fingers, range 6/6-no perception of light) (Wilcoxon sign rank test, p = 0.003), and was retained for a median of 3 months (1-91 weeks) after surgery. Poor visual outcome as evidenced by submedian final visual acuity was invariably associated with persistence of macular detachment, and significantly associated with the occurrence of optic atrophy (odds ratio = 5, p = 0.02). CONCLUSION: Retinal reattachment surgery appears justified in patients with herpesvirus retinitis and AIDS, but postoperative visual deterioration may occur in association with optic atrophy.

AIDS-Related Opportunistic Infections↗

Accuracy of visible retinal emboli for the detection of cardioembolic lesions requiring anticoagulation or cardiac surgery. Retinal Emboli of Cardiac Origin Study Group.

AIM: To determine the accuracy of visible retinal emboli as a diagnostic "test" for the likelihood of receiving anticoagulation or cardiac surgery based on the results of transthoracic echocardiography, in the setting of acute retinal arterial occlusion. METHODS: A multicentre retrospective diagnostic study at Kingston Eye Centre, Queen's University, Kingston, Ontario; Wills Eye Hospital, Philadelphia; Ottawa Eye Institute, Ottawa, Ontario; and the Halifax Infirmary, Halifax, Nova Scotia of 104 patients with both embolic and nonembolic acute retinal arterial obstruction who underwent transthoracic echocardiography was performed, to determine the accuracy of visible retinal emboli as a diagnostic "test" for anticoagulation or cardiac surgery. Anticoagulation or surgical intervention on the basis of abnormalities was detected solely through the technology of transthoracic echocardiography. RESULTS: 41 patients had visible retinal emboli (calcific, cholesterol, or fibrin). The remaining 63 had no evidence of embolic disease. The sensitivity of emboli for the likelihood of a patient receiving anticoagulation or cardiac surgery was 50%. The specificity, positive predictive value, and negative predictive value were 62%, 15%, and 90%, respectively. The likelihood ratio (LR = 1.31) obtained given the presence of a visible retinal embolus was neither clinically nor statistically significant (LR+ve = 1.31; 95% CI (0.91, 3.16)). This likelihood ratio, when applied to a patient with a pretest probability of 50%, results in a post-test probability of 56.7%. CONCLUSIONS: These results demonstrate that the presence of a visible retinal embolus should not be the sole determinant of whether to order transthoracic echocardiography, as the likelihood ratio for a patient receiving anticoagulation or cardiac surgery, given the presence of a visible retinal embolus was only 1.31.

Anticoagulants↗

Leptin stimulates ischemia-induced retinal neovascularization: possible role of vascular endothelial growth factor expressed in retinal endothelial cells.

Diabetic retinopathy is the leading cause of new blindness in adults in developed countries. Leptin, an adipocyte-derived hormone, stimulates endothelial proliferation and angiogenesis. This study was designed to elucidate the pathophysiologic role of leptin in the progression of retinal neovascularization. Using the retinopathy of prematurity model, a mouse model of ischemia-induced retinal neovascularization, we have demonstrated more pronounced retinal neovascularization in 17-day-old transgenic mice overexpressing leptin than in age-matched wild-type littermates. Ischemia-induced retinal neovascularization was markedly suppressed in 17-day-old leptin-deficient ob/ob mice. Western blot analysis revealed that a biologically active leptin receptor isoform is expressed in mouse retinal endothelial cells. Leptin receptor expression was also detected in primary cultures of porcine retinal endothelial cells, where it upregulated vascular endothelial growth factor (VEGF) mRNA expression. This effect was thought to be mediated at least partly through the activation of signal transducers and activators of transcription (STAT)3, because adenoviral transfection of the dominant-negative form of STAT3 abolished the leptin-induced upregulation of VEGF mRNA expression in retinal endothelial cells. This study provides evidence that leptin stimulates the ischemia-induced retinal neovasucularization possibly through the upregulation of endothelial VEGF, thereby suggesting that leptin antagonism may offer a novel therapeutic strategy to prevent or treat diabetic retinopathy.

Animals↗

A diffusible factor from normal retinal cells promotes rod photoreceptor survival in an in vitro model of retinitis pigmentosa.

Transgenic mice expressing a dominant mutation in the gene for the phototransduction molecule rhodopsin undergo retinal degeneration similar to that experienced by patients with the retinal degenerative disease, retinitis pigmentosa (RP). Although the mutation is thought to cause photoreceptor degeneration in a cell-autonomous manner, the fact that rod photoreceptor degeneration is slowed in chimeric wild-type/mutant mice suggests that cellular interactions are also important for maintaining photoreceptor survival. To more fully characterize the nature of the cellular interactions important for rod degeneration in the RP mutant mice, we have used an in vitro approach. We found that when the retinas of the transgenic mice were isolated from the pigmented epithelium and cultured as explants, the rod photoreceptors underwent selective degeneration with a similar time course to that observed in vivo. This selective rod degeneration also occurred when the cells were dissociated and cultured as monolayers. These data indicate that the mutant rod photoreceptors degenerate when removed from their normal cellular relationships and without contact with the pigmented epithelium, thus confirming the relative cell autonomy of the mutant phenotype. We next tested whether normal retinal cells could rescue the mutant photoreceptors in a coculture paradigm. Coculture of transgenic mouse with wild-type mouse or rat retinal cells significantly enhanced transgenic rod photoreceptor survival; this survival-promoting activity was diffusible through a filter, was heat labile, and not present in transgenic retinal cells. Several peptide growth factors known to be present in the retina were tested as the potential survival-promoting molecule responsible for the effects of the conditioned medium; however, none of them promoted survival of the photoreceptors expressing the Pro23His mutant rhodopsin. Nevertheless, we were able to demonstrate that the mutant photoreceptors could be rescued by an antagonist to a retinoic acid receptor, suggesting that the endogeneous survival-promoting activity may function through this pathway. These data thus confirm and extend the findings of previous work that local trophic interactions are important in regulating rod photoreceptor degeneration in retinitis pigmentosa. A diffusible factor found in normal but not transgenic retinal cells has a protective effect on the survival of rod photoreceptors from Pro23His mutant rhodopsin mice.

Animals↗

Retinal opacification after blunt non-perforating concussional injuries to the globe. A clinical and retinal fluorescein angiographic study.

Fluorescein angiographic studies are reported on fifteen patients presenting with retinal opacification after blunt mechanical non-perforating injuries involving the eye. In patients who subsequently regained full visual function and in whom complete resolution of the retinal changes occurred, retinal fluorography carried out less than 24 hours after injury revealed no abnormal features. In cases with more prolonged visual disability, retinal fluorescein examinations may, however, reveal damage to the retinal pigment epithelium before this becomes apparent on routine ophthalmoscopy, or the existence of impaired perfusion through the retinal vessels. It is suggested, therefore, that retinal fluorescein angiography has a role in assessing the visual prognosis in patients presenting with traumatic retinal oedema.

Adolescent↗

Ambient hypoxia reverses retinal vascular attenuation in a transgenic mouse model of autosomal dominant retinitis pigmentosa.

PURPOSE: Loss of retinal capillaries is an inherent component of late stage autosomal dominant retinitis pigmentosa (ADRP). This study examined the hypothetical role of tissue hyperoxia in this vascular attenuation process and tested the potential of ambient hypoxia to reverse it. METHODS: Transgenic mice expressing a mutant opsin gene with a 3-bp deletion of isoleucine at codon 255/256 were used. This model is characterized by early onset of a rapidly progressing retinal degeneration that by postnatal day (P)20 results in the loss of all but one row of photoreceptor nuclei. At P20 some mice were placed in 12% oxygen until they were euthanatized at P26. The remainder were maintained in normoxia and killed at the same age. Retinas were dissected, stained for ADPase, and flat-mounted. RESULTS: Deep plexus capillary density was significantly different in normoxic normals versus transgenics at 20 days of age (P: </= 0. 005). An additional 65% reduction of capillary density occurred within the deep plexus of normoxic transgenics between P20 and P26 (P: </= 0.005). Ambient hypoxia between days P20 and P26 reversed this trend, causing an increase in deep capillary plexus density of nearly 100% (P: </= 0.001). CONCLUSIONS: This model of ADRP demonstrates two important features of human retinitis pigmentosa: photoreceptor cell death and subsequent retinal capillary atrophy. Low ambient oxygen was used to reverse the capillary atrophy and to stimulate new capillary growth, implying that retinal oxygen tension may link these two features of the pathology. The implications of this study hold importance for strategies designed to treat retinitis pigmentosa with retinal cell transplantation.

Animals↗

Ocular blood flow and retinal metabolism in abyssinian cats with hereditary retinal degeneration.

PURPOSE: To investigate if retinal blood flow decreases with progression of the disease in Abyssinian cats with progressive retinal atrophy (PRA), to examine if the choroidal blood flow was affected by the disease, and to determine the uptake of glucose and formation of lactate in the outer retina. METHODS: Local blood flow in different parts of the eye was determined with radioactive microspheres, in 9 normal cats and in 10 cats at different stages of PRA. Three blood flow determinations were made in each animal, during control conditions, after IV administration of indomethacin and after subsequent administration of N(omega)-nitro-L-arginine (L-NA). Blood samples from a choroidal vein and a femoral artery were collected to determine the retinal formation of lactate and uptake of glucose. RESULTS: In Abyssinian cats with PRA (n = 10), the retinal blood flow was significantly (P < or = 0.01) lower than in normal cats (n = 9) during control conditions, 6.4 +/- 1.7 compared with 14.1 +/- 1.9 g min(-1) x (100 g)(-1). The vascular resistance in the iris and ciliary body was significantly higher in the cats at a late stage of PRA, both compared with normal cats and to cats at an early stage of the disease, whereas the choroidal vascular resistance was not significantly affected. Indomethacin had no effect on ocular blood flows in normal cats, but in cats with PRA, iridal blood flow was more than doubled after indomethacin. The retinal formation of lactate was significantly (P < or = 0.001) lower in cats with PRA than in normal cats, 0.111 +/- 0.035 (n = 8) compared with 0.318 +/- 0.024 (n = 8) micromol x min(-1). The uptake of glucose was not significantly different in cats with PRA. CONCLUSIONS: Retinal blood flow is severely decreased in Abyssinian cats at a late stage of retinal degeneration, whereas the choroidal microcirculation is not significantly affected by the disease. At a late stage of retinal degeneration, vascular resistance in the iris is significantly increased, which at least in part could be caused by cyxlooxygenase products.

Animals↗

Differential effects of bactericidal/permeability-increasing protein (BPI) analogues on retinal neovascularization and retinal pericyte growth.

PURPOSE: Bactericidal/permeability-increasing protein (BPI), an antibacterial and lipopolysaccharide-neutralizing protein, also has an antiangiogenic effect. To evaluate the therapeutic role of BPI in ischemic retinopathies, the antiangiogenic activity of a human recombinant 21-kDa modified N-terminal fragment of BPI (rBPI(21)), which has the biological properties of the holoprotein, and a peptidomimetic (XMP.Z) derived from BPI were examined. METHODS: The effects of rBPI(21) and XMP.Z on VEGF-induced growth of bovine retinal microvascular endothelial cells (BRECs) and on serum-induced growth of bovine retinal pericytes (BRPs) and retinal pigment epithelial cells (BRPECs) were evaluated by determining total DNA content. The neonatal mouse model of retinopathy of prematurity (ROP) was used to study the effect of XMP.Z in vivo. Intraperitoneal injections of the peptidomimetic (10 mg/kg) were administered every 24 hours for 5 days (postnatal [P]12-P17) during induction of neovascularization. Retinal neovascularization was evaluated using flatmounts of fluorescein-dextran-perfused retinas and quantitated by counting retinal cell nuclei anterior to the internal limiting membrane. RESULTS. VEGF (25 ng/mL) increased the total DNA per well of BRECs by 120% +/- 50% (P < 0.001), which was inhibited by addition of rBPI(21) or XMP.Z, with decreases of 77% +/- 15% (P < 0.05) and 107% +/- 19% (P < 0.01) at maximum effective doses of 75 and 15 microg/mL rBPI(21) and XMP.Z, respectively. In contrast, rBPI(21) at 75 microg/mL enhanced the total DNA per well of BRP 53% +/- 14% (P < 0.001) in the presence of 5% fetal bovine serum (FBS), whereas XMP.Z enhanced BRP growth by 27% +/- 7% (P < 0.001) at 5 microg/mL. In the presence of 10% FBS, rBPI(21) and XMP.Z increased BRP growth by 91% +/- 35% (P < 0.001) and 43% +/- 18% (P < 0.01), respectively. In the oxygen-induced ROP neonatal mouse model, retinal neovascularization was decreased by 40% +/- 16% (n = 5, P < 0.01) when animals were treated with XMP.Z. CONCLUSIONS: Two BPI-derived compounds, rBPI(21) and XMP.Z, significantly suppressed VEGF-induced BREC growth in vitro, while conversely enhancing the growth of BRPs, even above that induced by 20% FBS. When tested in animals, XMP.Z also suppressed ischemia-induced retinal neovascularization in mice. These data suggest that BPI-derived compounds may have unique therapeutic potential for proliferative retinal diseases such as diabetic retinopathy, if physiological levels can be achieved in clinical settings.

Animals↗

Retinal detachment in cytomegalovirus retinitis: intravenous versus intravitreal therapy.

PURPOSE: To compare the rate of retinal detachment in a group of patients treated with intravitreal ganciclovir to the rate of retinal detachment in a group of patients treated with systemic ganciclovir. METHODS: A retrospective non-randomized comparative case series was conducted. The participants were 186 consecutive patients with cytomegalovirus (CMV) retinitis treated at two centres over the period from June 1990 to May 1997. Of the 186, 133 patients had systemic therapy of whom 113 had intravenous ganciclovir or foscarnet and 20 had oral ganciclovir, and 53 patients had intravitreal induction and maintenance therapy. The main outcome measure was the rate of retinal detachment, which was calculated using person-months-at-risk denominators. The effect measure used in the main comparative analysis was the hazard ratio obtained from multiple regression using the Cox proportional hazards model. RESULTS: Retinal detachment occurred in three of 53 patients in the intravitreal therapy group, one of 20 patients receiving oral maintenance therapy and 21 of 113 patients receiving intravenous maintenance therapy. The risk of retinal detachment with systemic therapy was 14-fold higher than with intravitreal therapy (P < 0.001)and up to fourfold higher with oral maintenance therapy. CONCLUSIONS: Intravitreal therapy offers a significant advantage over systemic therapy in the treatment of CMV retinitis by substantially reducing the risk of CMV-related retinal detachment.

AIDS-Related Opportunistic Infections↗

Rhegmatogenous retinal detachments in patients with AIDS and necrotizing retinal infections.

Rhegmatogenous retinal detachments can occur in patients with acquired immune deficiency syndrome (AIDS) and necrotizing retinal infections. Of 68 patients with AIDS and necrotizing retinal infections seen between 1983 and 1987, rhegmatogenous retinal detachments developed in 16 patients (27 eyes). In this group, cytomegalovirus retinopathy was present in 75% (12 of 16) of patients, 18.8% (3 of 16) had probable herpes simplex virus retinopathy, and 6.2% (1 of 16) had toxoplasmic retinochoroiditis. Retinal detachment was bilateral in 68.8% (11 of 16) of patients. The retina was reattached successfully in 91% (10 of 11) of operated eyes. Proliferative vitreoretinopathy was present preoperatively in 95% of these eyes. Seven of 11 operated eyes had initial improvement in visual acuity. However, 5 of 11 continued to lose vision despite successful reattachment. Techniques included pneumatic reattachment, scleral buckle, vitrectomy, and silicone oil injection. Complicated retinal detachments in AIDS patients with rhegmatogenous retinal detachments and necrotizing retinal infections are common and can be repaired, but the prognosis is guarded in many patients.

Acquired Immunodeficiency Syndrome↗

Quantitative evaluation for blood-retinal barrier breakdown in experimental retinal vein occlusion produced by photodynamic thrombosis using a new photosensitizer.

Purpose. To establish a rat model of retinal vein occlusion (RVO), we applied photodynamic thrombosis using a new photosensitizer. By measuring the breakdown of the blood-retinal barrier (BRB), we evaluated the model quantitatively. We also investigated how hypertension and retinal pigment epithelium (RPE) influence the breakdown of BRB after RVO. Methods. We modified a slit lamp biomicroscope for photodynamic thrombosis. The light source was changed from white light to argon laser, which made it possible to perform fluorescein angiography (FAG) simultaneously during photodynamic thrombosis. We irradiated with a continuous diode laser to occlude three retinal veins in a rat after PAD-S31 injection. The breakdown of BRB was quantitated by measuring extravasated Evans blue dye in albino and pigmented rats. We compared hypertensive rats (SHR) to normotensive rats (WKY) and sodium iodate-treated rats to normal rats. Results. High photosensitivity of PAD-S31 made it possible to occlude any retinal veins within 120 seconds at a low dose of 10 mg/kg without retinal thermal burn at the occlusion site. Simultaneous FAG enabled us to observe the formation of thrombus during diode laser irradiation. Our measured value of intraretinal Evans blue correlated with the range of serous retinal detachment. Both albino and pigmented rats demonstrated stable and constant values of Evans blue. SHR recovered from the breakdown of BRB after venous occlusion more slowly than WKY. Sodium iodate-treated rats had smaller breakdowns of BRB and recovered earlier than normal rats. Conclusions. In this study, we established the stable and constant rat model of RVO efficiently by using a new photosensitizer. Our simultaneous FAG method was considered to have an advantage of several potential clinical applications. Our rat model of RVO allows us to study factors associated with the recovery from damage by RVO.

Animals↗

Cilio-retinal arterial circulation in central retinal vein occlusion.

The hypothesis that an occlusion of the central retinal artery is an essential prerequisite for haemorrhage formation after central retinal vein obstruction has been investigated by examining the fundus changes in patients with a cilio-retinal arterial circulation; the findings are at variance with the 'combined occlusion hypothesis'. Comparisons were made between the pathological features in two retinal capillary beds with independent sources of arterial supply--namely, the central retinal and cilio-retinal arteries--but with an obstructed venous drainage channel common to both--namely, the central retinal vein. The importance of intraluminal pressure changes (as distinct from perfusion changes) in the causation of haemorrhages and oedema after venous occlusion is stressed, and the role of arterial disease in the pathogenesis of venous occlusions is distinguished from its role in determining the sequelae of such occlusions.

Adult↗

Persistent foveal retinal detachment after successful rhegmatogenous retinal detachment surgery.

PURPOSE: To describe the tomographic features of the neurosensory retina after successful rhegmatogenous retinal detachment surgery. DESIGN: Cohort study. METHODS: We prospectively examined cross-sectional retinal images using optical coherence tomography (OCT) in 15 eyes of 15 consecutive patients (mean age, 46 years) who underwent scleral buckling surgery for treatment of rhegmatogenous retinal detachment. The retinas appeared reattached upon binocular stereoscopic indirect ophthalmoscopy. All eyes were examined at 1, 3, 6, and 12 months postoperatively. The time from onset of subjective symptoms of retinal detachment to retinal surgery ranged from 4 to 66 days (mean, 14 days). The postoperative OCT findings and best-corrected visual acuity were statistically analyzed using the Mann-Whitney U test. RESULTS: The detached retinas appeared attached on ophthalmoscopy in all eyes 1 month postoperatively. OCT showed residual retinal detachment in four eyes (27%) at the fovea and in three eyes (20%) at the fovea and adjacent area. The remaining eight retinas (53%) were attached when examined tomographically. In six of the seven eyes with residual foveal detachment by OCT, the retinas reattached spontaneously up to 12 months postoperatively. The postoperative best-corrected visual acuity improved gradually during 12 postoperative months in all 15 eyes. A substantial increase in visual acuity occurred when the fovea reattached in the six eyes with residual detachment. CONCLUSIONS: Foveal retinal detachment may persist after successful retinal detachment surgery in eyes in which the fovea appeared to be attached on ophthalmoscopy. The residual foveal detachment may explain, in part, the delayed visual acuity improvement after successful scleral buckling.

Adolescent↗

Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo.

Leukocyte adhesion to the diabetic retinal vasculature results in early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Previous work has shown that intercellular adhesion molecule-1 (ICAM-1) and CD18 are required for these processes. However the relevant in vivo stimuli for ICAM-1 and CD18 expression in diabetes remain unknown. The current study investigated the causal role of endogenous vascular endothelial growth factor (VEGF) and nitric oxide in initiating these events. Diabetes was induced in Long-Evans rats with streptozotocin, resulting in a two- to threefold increase in retinal leukocyte adhesion. Confirmed diabetic animals were treated with a highly specific VEGF-neutralizing Flt-Fc construct (VEGF TrapA(40)). Retinal ICAM-1 mRNA levels in VEGF TrapA(40)-treated diabetic animals were reduced by 83.5% compared to diabetic controls (n = 5, P < 0.0001). VEGF TrapA(40) also potently suppressed diabetic leukocyte adhesion in retinal arterioles (47%, n = 11, P < 0.0001), venules (36%, n = 11, P < 0.0005), and capillaries (36%, n = 11, P < 0.001). The expression of endothelial nitric oxide synthase (eNOS), a downstream mediator of VEGF activity, was increased in diabetic retina, and was potently suppressed with VEGF TrapA(40) treatment (n = 8, P < 0.005). Further, VEGF TrapA(40) reduced the diabetes-related nitric oxide increases in the retinae of diabetic animals. The inhibition of eNOS with N-omega-nitro-L-arginine methyl ester also potently reduced retinal leukocyte adhesion. Although neutrophil CD11a, CD11b, and CD18 levels were increased in 1-week diabetic animals, VEGF TrapA(40) did not alter the expression of these integrin adhesion molecules. Taken together, these data demonstrate that VEGF induces retinal ICAM-1 and eNOS expression and initiates early diabetic retinal leukocyte adhesion in vivo. The inhibition of VEGF bioactivity may prove useful in the treatment of the early diabetic retinopathy.

Animals↗

Extended retinal tamponade in the treatment of retinal detachment with proliferative vitreoretinopathy.

We have used intraocular sulphur hexafluoride or liquid silicone as an adjunct to vitreous surgery in the treatment of a non-randomised sequential series of 19 eyes with retinal detachment complicated by proliferative vitreoretinopathy. We have studied the surgical results and complications of these two tamponades and drawn preliminary conclusions on their use in retinal reattachment surgery. After a seven-month minimum follow-up 13 (68%) of the eyes have reattached retinas. Six (60%) of 10 eyes treated only with silicone have reattached retinas, and four (67%) of six eyes treated only with sulphur hexafluoride gas tamponade have reattached retinas. An additional three eyes treated initially with silicone oil subsequently developed retinal detachments; all were successfully reattached with sulphur hexafluoride tamponade after silicone oil removal. Intraoperative pneumatic retinal reattachment to assess relief of retinal traction combined with the production of widespread chorioretinal adhesions to wall off persistent anterior traction and detachment, as well as extended postoperative gas tamponade of the retina, appears to enhance the surgical results in retinal detachment complicated by proliferative vitreoretinopathy. Silicone oil tamponade of the retina appears to be useful in cases where retinal traction cannot be entirely relieved and in patients who are unable to tolerate the head positioning required for effective gas tamponade of the retina. A controlled clinical study recently begun will be required to define further the precise role of these methods of retinal tamponade.

Adult↗

Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa.

PURPOSE: To map the spatiotemporal decline in retinally driven activity in the superior colliculus (SC) of transgenic S334ter-line-3 rats that express a mutated rhodopsin, which causes photoreceptor degeneration. To determine whether transplantation of fetal retinal sheets into the subretinal space of these rats can recover visual activity in the SC. METHODS: A visual stimulus was presented to the eye, and responses were recorded across the SC of untreated S334ter-line-3 rats aged 28 to 288 days. These data were used to draw a map of the developing scotoma. Intact retinal sheets from embryonic day 19 rats were transplanted into the subretinal space of S334ter-line-3 rats between 21 and 28 days of age. Responses to retinal stimulation were mapped in the SC of transplanted and sham control rats 78 to 163 days after surgery. The morphology of the retinas in all groups was examined. RESULTS: Photoreceptor cell loss in untreated rats matched the decline in visual activity in the SC. At 28 days, there was a scotoma in the area of the SC that represents the central retina and, by 63 days, it had enlarged to cover the entire retinal representation. Visual responses were evoked in 64% of rats with retinal transplants. These retinally driven responses were confined to a small, contiguous region of the SC that represents the sector of the retina where the transplant was placed. Visual responses were absent in the SC outside this area in transplant recipients and throughout the SC of untreated and sham control rats. CONCLUSIONS: Transplantation of fetal retinal sheets induced recovery of visual activity in the SC in this model of RP. The mechanisms underlying this functional recovery remain to be resolved, but these results suggest that transplantation should be further explored as a therapy for RP.

Animals↗

Role of neurotrophin-4/5 in neural cell death during retinal development and ischemic retinal injury in vivo.

PURPOSE: Neurotrophin (NT)-4/5 and brain-derived neurotrophic factor (BDNF) mediate cell survival through TrkB, a high-affinity tyrosine kinase receptor, and may prevent neural cell death in various pathologic conditions. This study was conducted to investigate the function of NT-4/5 in neural cell death during retinal development and ischemic retinal injury. METHODS: Retinal development in wild-type, NT-4/5 knockout (KO), and NT-4/5:BDNF double-KO mice was histologically examined from postnatal day 0 (P0) to P90. Ischemic retinal injury was performed at P42, and NT-4/5 mRNA expression level and the extent of retinal cell death was quantitatively examined. RESULTS: Real-time PCR analysis revealed increased NT-4/5 mRNA expression in the ischemic retina. In the NT-4/5 KO mouse, retinal development and structure were normal, but the strain was susceptible to ischemic injury on P42. In contrast, NT-4/5:BDNF double-KO mice showed delayed retinal development and died before P42. CONCLUSIONS: These results suggest that NT-4/5, in combination with other trophic factors, is involved in the postnatal survival of retinal neurons during both development and degeneration.

Animals↗