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PubMed2006

A comparison of neural differentiation and retinal transplantation with bone marrow-derived cells and retinal progenitor cells.

Retinal progenitor cells (RPCs) are immature precursors that can differentiate into retinal neurons, including photoreceptors. Recently, it has been reported that bone marrow-derived cells may also be capable of differentiation into cells of central nervous system lineage, including retinal neurons. We compared these two cell types to evaluate their potential as a source of cells for retinal transplantation. Marrow stromal cells (MSCs) and macrophages were isolated from enhanced green fluorescence protein mice. MSCs were cultured with brain-derived neurotrophic factor, nerve growth factor, and basic fibroblast growth factor to induce neuronal differentiation. RPCs were cultured under the same conditions or with 10% fetal bovine serum. Neuronal marker expression was examined and compared between MSCs and RPCs. MSCs, macrophages, and RPCs were also cultured with explanted retinas from rhodopsin knockout mice to study their potential for retinal integration. MSCs expressed neuronal and retina-specific markers by reverse transcription-polymerase chain reaction and immunocytochemistry. Both types of cells migrated into retinal explants and expressed neurofilament 200, glial fibrillary acidic protein, protein kinase C-alpha, and recoverin. RPCs expressed rhodopsin, a photoreceptor marker we never detected in MSCs. A majority of bone marrow derived-macrophages differentiated into cells that resembled microglia, rather than neural cells, in the explanted retina. This study shows that RPCs are likely to be a preferred cell type for retinal transplantation studies, compared with MSCs. However, MSCs may remain an attractive candidate for autologous transplantation.

Animals↗

PubMed1978

Experimental retinal vascular occlusion. I. Pathogenesis of central retinal vein occlusion.

In 45 eyes of rhesus monkeys, five types of central retinal vascular occlusion were produced by lateral orbitotomy: group 1, central retinal vein occlusion (CRVO) alone; group 2, CRVO with simultaneous central retinal artery (CRA) occlusion; group 3, CRVO with transient clamping of the CRA for either 2 to 2 1/2 hours (group 3A) or 6 to 7 1/2 hours (group 3B); and group 4, CRVO with segmental retinal ischemia. The eyes were examined by fundus photography and fluorescein angiography for up to nine months. Group 1 developed venous stasis retinopathy (VSR) and group 3B hemorrhagic retinopathy (HR). In group 4 the ischemic and nonischemic segments of the retina developed segmental HR and VSR, respectively. Groups 2 and 3A developed neither VSR nor HR. Retinal capillary obliteration occurred in groups 2 and 3B and in the ischemic part of group 4, starting one to three weeks after the occlusion and progressing thereafter. These studies indicate that clinically co-called CRVO consists of two distinct entities: VSR and HR, with retinal ischemia playing an important role in the production of HR. On the basis of the present and other available information, the pathogenesis of CRVO was concluded to be multifactorial.

Animals↗

PubMed2006

Evaluation of residual retinal function by pupillary constrictions and phosphenes using transcorneal electrical stimulation in patients with retinal degeneration.

BACKGROUND: To evaluate inner-retinal function by pupillary constrictions and phosphenes evoked by transcorneal electrical stimulation (TES) in patients with hereditary retinal degeneration. METHODS: Consecutive 20 eyes of 20 patients (16 with retinitis pigmentosa (RP); and four with cone-rod dystrophy (CRD)) whose visual acuity was equal to or worse than 20/2000 at Osaka University Hospital and eight eyes of eight healthy subjects were enrolled. TES was performed on with a contact lens stimulating electrode. The electrically evoked pupillary response (EEPR) was recorded by a pupillometer, and the phosphenes by the subjective responses. Three electrical current thresholds were determined: T1, threshold current for initial phosphene; T2, threshold for eliciting a phosphene extending into the central field; and P, threshold for a relative pupillary constriction > or = 3%. The EEPR and phosphene thresholds were compared with the visual acuity or the visual field. RESULTS: All T1, T2 and P were significantly higher in patients than in normals (Mann-Whitney, P<0.001). Both T1 and T2 were not correlated with visual acuity but depended on the area and location of the residual visual field. T1 and T2 in RP eyes with a EEPR was significantly lower than that in RP eyes without an EEPR. During TES, all subjects and patients had no pain, and no complications except for a slight corneal superficial punctuate keratopathy. CONCLUSIONS: The safety and the efficacy of TES to estimate the residual inner-retinal function in patients with retinal degeneration indicate that TES can be used as one of the most important test to select candidates for retinal prostheses.

Adult↗

PubMed2006

Recombinant alpha2(IV)NC1 domain of type IV collagen is an effective regulator of retinal capillary endothelial cell proliferation and inhibits pre-retinal neovascularisation.

BACKGROUND: A recombinant form of the alpha2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined the potential for alpha2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo assay systems. MATERIALS AND METHODS: alpha2(IV)NC1 at concentrations between 0.1 and 1 mug/ml was added to retinal microvascular endothelial cells (RMECs) followed by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional retinal angiogenesis assay and the number of angiogenic sprouts quantified. alpha2(IV)NC1 was also delivered intra-vitreally to mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated controls. RESULTS: RMECs treated with alpha2(IV)NC1 (0.1, 0.5 and 1 microg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with alpha2(IV)NC1 showed no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was significantly reduced by alpha2(IV)NC1 at 0.5 microg/ml (P<0.01). alpha2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in vitro (P<0.001). Intra-vitreal injection of alpha2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared with vehicle-treated controls (P<0.001). CONCLUSION: alpha2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment of neovascularisation in proliferative retinopathies.

Animals↗

PubMed1975

Rhegmatogenous retinal detachment after tributary retinal vein occlusion.

Two patients had rhegmatogenous retinal detachment after tributary retinal vein occlusion. Neovascularization adherent to the posterior hyaloid was avulsed, along with a plug of retinal tissue, as the vitreous body collapsed. Localized retinal detachments resulted. Photocoagulation successfully obliterated the retinal holes and prevented extension of the retinal detachments in both cases.

Female↗

PubMed1986

Retinal fluorescein leakage in retinitis pigmentosa.

Of 82 consecutive patients with retinitis pigmentosa, 78 underwent fluorescein angiography using standard and special, abbreviated photographic protocols. The stereoscopic angiograms disclosed alterations of the blood-retinal barrier, primarily at the level of the retinal pigment epithelium, in 60 patients. Areas of leakage were bilateral in all but two persons. The macula most frequently showed leakage, followed by the optic disk, the arcade areas, and the periphery. A few individuals exhibited leakage from the perifoveal retinal vessels. None of these patients had significant retinal vascular alterations or exudates in the retinal periphery. In eyes with no cataract or detectable macular pigment change and with comparable amounts of epiretinal membrane, the presence of macular edema was significantly correlated with reduced central visual acuity.

Adolescent↗

PubMed2004

Delayed absorption of macular edema accompanying serous retinal detachment after grid laser treatment in patients with branch retinal vein occlusion.

PURPOSE: To study the detailed process of macular edema (ME) absorption after grid laser photocoagulation in patients with branch retinal vein occlusion (BRVO). The influence of pretreatment serous retinal detachment (SRD) at the fovea on patient outcome was also evaluated. DESIGN: Retrospective, interventional, comparative case series. PARTICIPANTS: Thirty-seven BRVO patients presenting with severe ME. METHODS: Patients were treated with grid laser photocoagulation with 6 months of follow-up examinations. Baseline and post-treatment examinations included measurements of visual acuity (VA), fluorescein angiography, and detailed imaging of ME by optical coherence tomography (OCT). Macular thickness was defined as the distance from the inner retinal surface to the outer border of the sensory retina (foveal retinal thickness) and also to the inner border of the retinal pigment epithelium including the SRD (total foveal elevation). MAIN OUTCOME MEASURES: Post-treatment macular thickness with OCT, VA converted to the logarithm of the minimum angle of resolution, and absorption of SRD, and correlations of macular thickness and VA both before and after treatment. RESULTS: Total foveal elevation and VA were significantly improved at 1, 3, and 6 months after treatment. There was also a significant correlation between reduction of total foveal elevation and increase in VA. Fourteen eyes (37.8%) displayed SRD, as evidenced by OCT at the baseline. In eyes without SRD, foveal retinal thickness and VA had significantly improved in a time-dependent manner. However, although SRD itself was almost absorbed 6 months after treatment, the improvement of both VA and total foveal elevation in eyes with pretreatment SRD was not significant compared with baseline conditions. Both post-treatment total foveal elevation and VA of eyes with SRD tended to be worse than eyes without SRD. CONCLUSION: The presence of subfoveal SRD retards the absorption of ME and recovery of VA after grid laser photocoagulation in patients with BRVO.

Absorption↗

PubMed2003

Peripheral retinal degenerations and the risk of retinal detachment.

PURPOSE: To review the degenerative diseases of the peripheral retina in relationship with the risk to develop a rhegmatogenous retinal detachment and to present recommendations for use in eyes at increased risk of developing a retinal detachment. DESIGN: Focused literature review and author's clinical experience. RESULTS: Retinal degenerations are common lesions involving the peripheral retina, and most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and, rarely, zonular traction tufts, can result in a rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic therapy; however, adequate studies have not been performed to date. CONCLUSIONS: Well-designed, prospective, randomized clinical studies are necessary to determine the benefit-risk ratio of prophylactic treatment. In the meantime, the evidence available suggests that most of the peripheral retinal degenerations should not be treated except in rare, high-risk situations.

Humans↗

PubMed1993

Hyperhomocysteinemia in retinal artery and retinal vein occlusion.

In 19 patients who had retinal vein occlusion or retinal artery occlusion before the age of 50 years, the incidence of hyperhomocysteinemia, as observed in heterozygosity for homocystinuria, was studied by the performance of a standardized, oral methionine-loading test. In four of the 19 patients (21%), two with retinal artery occlusion and two with central retinal vein occlusion, the after-load peak levels of homocysteine exceeded the mean level, established in normal control subjects, by more than two standard deviations and were as well within the ranges established in obligate heterozygotes for homocystinuria. Because the frequency of heterozygosity for homocystinuria in the normal population is one in 70 (1.4%) at the most, we conclude that hyperhomocysteinemia predisposes to the development of premature retinal artery and retinal vein occlusion (P < .01; chi 2 test).

Adult↗

PubMed1998

Treatment of central retinal vein occlusion by injection of tissue plasminogen activator into a retinal vein.

PURPOSE: To report the injection of tissue plasminogen activator into a retinal vein to treat central retinal vein occlusion. METHODS: An 81-year-old woman with visual loss of the right eye secondary to central retinal vein occlusion developed central retinal vein occlusion and visual loss in her left eye. Treatment of her left eye with topical ocular hypotensive medications, pentoxifylline, and laser chorioretinal anastomosis was without benefit. Thereafter, she underwent vitreoretinal surgery, including tissue plasminogen activator injection into a branch retinal vein of her left eye. RESULTS: The patient reported subjective improvement in the vision of her left eye. Ophthalmoscopic and fluorescein angiographic improvement were also noted. CONCLUSION: The feasibility of cannulating a retinal vein for treatment has been demonstrated.

Aged↗

PubMed2001

Subclinical retinal detachment resulting from asymptomatic retinal breaks: prognosis for progression and regression.

PURPOSE: To give a more accurate epidemiologic description of subclinical retinal detachments and to learn their prognosis. DESIGN: Prospective, natural history cohort study. PARTICIPANTS: Seventeen patients, with 19 eyes involved with 22 separate areas of subclinical retinal detachment (SCRD). Ages at initial diagnosis ranged between 14 and 67 years. METHODS: Periodic retinal examinations over follow-up periods of between 8 months and >33 years, using indirect ophthalmoscopy and scleral indentation, and sometimes slit-lamp vitreous examinations with Goldmann lens. MAIN OUTCOME MEASURES: Documentation with written descriptions and drawings of lesions and estimation of size and dimensions. RESULTS: The rate of progression to clinical retinal detachment (CRD), which involved 11% of eyes (2 of 18), was found to be exactly equal to the likelihood of spontaneous regression and disappearance, also found in 11% (2 of 18), without any treatment. The calculated incidence rate of progression to CRD was 0.008 (<1% per year). Also, myopic females were found to have a 4.7-times greater risk of subclinical retinal detachment developing than were males, P = 0.036. All of these findings are reported for the first time in the ophthalmic literature. CONCLUSIONS: Compared with symptomatic clinical retinal detachment, SCRD is much less threatening to the vision and the health of the eye. Therefore, SCRD does not require or justify routine treatment but should be reexamined at regular annual intervals or more frequently if changes are observed. If it definitely progresses to CRD, surgical treatment is justified.

Adolescent↗

PubMed2001

Injection of tissue plasminogen activator into a branch retinal vein in eyes with central retinal vein occlusion.

PURPOSE: Central retinal vein occlusion (CRVO) often produces significant and permanent loss of vision in the affected eye. The purpose of this study was to determine if patients with vision loss secondary to CRVO treated with retinal vein cannulation and infusion of tissue plasminogen activator (t-PA) experienced recovery of visual acuity. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Thirty eyes of 30 consecutive patients with CRVO underwent the procedure, but two were subsequently excluded. The remaining 28 eyes of 28 patients with CRVO for an average of 4.9 months before intervention (range, 0.25-30 months) and best-corrected visual acuity 20/63 or worse were included in the study. INTERVENTION: All patients underwent pars plana vitrectomy with cannulation and infusion of t-PA into a branch retinal vein. MAIN OUTCOME MEASURES: Change in visual acuity and the development of complications such as vitreous hemorrhage and neovascular glaucoma were monitored. RESULTS: Twenty-two of 28 patients (79%) experienced at least one line of visual improvement during the follow-up period (average, 11.8 months; range, 3-24 months), and the same number had this level of improvement at the last follow-up examination. Fifteen patients (54%) gained 3 or more lines of acuity within 6 months after the procedure, and 14 (50%) had acuity at last follow-up at least 3 lines better than baseline acuity (average, 6.8 lines). Seven patients had postoperative vitreous hemorrhages ranging from 1 week to 11 months after the procedure; two cleared spontaneously. One patient had a postoperative retinal detachment from a peripheral retinal break that was repaired successfully with pneumatic retinopexy. No other serious intraoperative or early postoperative complications were noted. CONCLUSIONS: Vitrectomy with retinal vein cannulation and infusion of t-PA is a relatively safe procedure that may improve vision in eyes with CRVO.

Aged↗

PubMed1985

Progressive inherited retinal arteriolar tortuosity with spontaneous retinal hemorrhages.

Tortuosity of the retinal arterioles complicated by spontaneous retinal hemorrhages is inherited as an autosomal dominant trait. Even when hemorrhages involve the fovea, spontaneous clearing with recovery of normal vision is the rule. We have studied members of three families in which arteriolar tortuosity increases with age. Tortuosity increases most dramatically during adolescence and affects small arterioles in the macular area. Retinal hemorrhages in children from two pedigrees led to extensive laboratory investigation because arteriolar tortuosity, later unmistakeable, was not recognized initially. Inherited retinal arteriolar tortuosity may be overlooked easily, particularly in children. Patients with spontaneous retinal hemorrhages and their relatives should be examined for retinal arteriolar tortuosity before being subjected to cardiovascular or hematologic studies.

Adolescent↗

PubMed1992

Management of retinal detachment associated with CMV retinitis in AIDS patients.

In patients with AIDS, the most important ocular opportunistic infection, CMV retinitis, can now be treated effectively with virostatic agents. Associated retinal detachment is encountered frequently, and its management has become increasingly significant to quality of life as improvements in medical care have helped to preserve vision and extend life expectancy. Although retinal detachment in these eyes is typically rhegmatogenous, the pathophysiology is distinctive due to the association with CMV retinitis which, even in remission, is characterised by atrophic changes at all levels of affected retina and alterations of the vitreous. Despite initially successful surgical reattachment, multiple, small, often posterior holes may develop because of progressive CMV infection. For these reasons, vitrectomy and silicone oil injection with scleral buckling may currently provide the best overall means of maintaining retinal reattachment and restoring visual function. Nevertheless, management must be individualised in each case, with the realisation that progressive visual loss frequently ensues from retinitis progression.

AIDS-Related Opportunistic Infections↗

PubMed1995

Progressive outer retinal necrosis (PORN) in AIDS patients: a different appearance of varicella-zoster retinitis.

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

AIDS-Related Opportunistic Infections↗

PubMed2003

Comparison of scleral buckling with combined scleral buckling and pars plana vitrectomy in the management of rhegmatogenous retinal detachment with unseen retinal breaks.

BACKGROUND: The purpose of the present paper was to compare the techniques of conventional scleral buckling and combined pars plana vitrectomy and scleral buckling procedures in rhegmatogenous retinal detachments with unseen retinal breaks. METHODS: Forty-four consecutive eyes with uncomplicated, primary rhegmatogenous retinal detachments with a clear media and unseen retinal breaks were randomized to two groups. The scleral buckling group underwent 360 degrees scleral buckling, cryopexy and external subretinal fluid drainage. In the combined surgery group, 360 degrees scleral buckling, pars plana vitrectomy, air-fluid exchange, endolaser and injection of 14% perfluoropropane gas was done. RESULTS: At 3 months follow up the primary reattachment rate was 80% (16/20 cases) in the combined surgery group, and 70% (14/20 cases) in the scleral buckling group (P = 0.716). The visual acuity improved significantly from a preoperative median of hand movement (HM; range: HM to 6/60; similar in both the groups), to a median of 6/60 (range: perception of light to 6/18) in the combined surgery group and a median of 6/36 (range: HM to 6/18) in the scleral buckling group, the difference between the two groups not being statistically significant (P = 0.4). The number of intraoperative and postoperative complications was more in the combined surgery group. (four cases were lost to follow up and were doing well when last examined.) CONCLUSION: Conventional scleral buckling was found to be a safe and effective technique in the primary management of uncomplicated, rhegmatogenous retinal detachments with unseen retinal breaks when the media is clear.

Adolescent↗

PubMed2002

Ganglion cell responses to retinal light stimulation in the absence of photoreceptor outer segments from retinal degenerate rodents.

PURPOSE: To determine whether a severely degenerated retina without photoreceptor outer segments and a non-recordable electroretinogram (ERG) can still show retinal ganglion cell (RGC) responses to retinal light stimulation. METHODS: The authors measured ERGs and retinal surface RGC responses from six week old rd mice and three month old homozygous S334ter line3 rats. Animal eyes were also studied by light microscopy, transmission electron microscopy, and immunohistochemistry (rats). RESULTS: The corneal ERGs were non-recordable and no photoreceptor outer segments were found in either retinal degeneration model. A few cell bodies (without outer segments) that were immunoreactive for cone opsin and rhodopsin were found in the outer nuclear layer of the rats. Light-driven ON-RGC responses, however, were recordable from six week old rd mice. In addition, light-driven ON and OFF-RGC responses were recordable from three month old homozygous S334ter line 3 rats. CONCLUSIONS: This study suggests that despite the apparent absence of photoreceptor outer segments and a non-recordable ERG, ganglion cell responses to retinal light stimulation may remain preserved in some severe retinal degenerate transgenic rodents.

Animals↗

PubMed1999

Evaluation of the role of human retinal vascular endothelial cells in the pathogenesis of CMV retinitis.

Previous studies of cytomegalovirus (CMV) retinitis have failed to definitively explain the exact mechanism by which CMV gains access to and initiates infection in the retina. Proposed theories have included leakage of the virus through vessels with altered permeability, with subsequent infection of surrounding glial cells. In an attempt to shed further light on this subject, a histopathologic examination of 30 autopsy eyes from patients with known systemic CMV disease was carried out using light microscopy, immunohistochemical and immunofluorescent techniques, and in-situ hybridization. Dual-staining methods were used to identify the exact cell type showing the presence of CMV antigens, namely vascular endothelial cells, glial cells, neuronal cells, and/or leukocytes. In those eyes with CMV retinitis, the sites of full-thickness retinal necrosis revealed viral presence mostly within Müller cells and perivascular glial cells, with focal areas of positive staining within retinal pigment epithelial cells (RPE) and neuronal cells. The retinal capillaries were devoid of endothelial cells in these areas. Adjacent to regions of full-thickness necrosis, some vessels showed the presence of a viral antigen within the endothelial cells. These findings suggest that retinal vascular endothelial cells can be infected with CMV. It can further be hypothesized that infection of vascular endothelial cells leads to infection of the surrounding glial and neuronal cells, with eventual spread to the RPE. Endothelial cells might not be present in areas of full-thickness necrosis due to mechanical forces from adjacent blood flow resulting in the sloughing of these cells.

Capillaries↗