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[Results of posterior chamber lens implantation with trans-scleral sulcus suture fixation].

BACKGROUND: Transscleral fixation of a posterior chamber intraocular lens has been proposed in eyes lacking adequate posterior capsular support. METHODS: We performed a retrospective review of 38 eyes of 38 patients who had a 12 months follow-up. Visual acuity, intraocular pressure and complications have been studied. We performed a transscleral fixation of posterior chamber lens with the following indications: 1. planned intraocular cataract extraction; 2. following intraoperative complications of phacoemulsification; 3. in combination with perforating keratoplasty; 4. in combination with parsplana vitrectomy. RESULTS: There were no serious intra- or shortly postoperative complications. 34% of the implanted lenses were not perfectly positioned. Up to 12 months, there were only minor problems in the anterior segment (suture erosions, anterior synechiae, iris capture). As longterm postoperative complications one patient developed retinal detachment, 3 others proliferative vitreoretinopathy after previous retinal detachment surgery. Two patients developed new onset glaucoma, and 3 glaucoma patients showed a medically uncontrollable intraocular pressure postoperatively. CONCLUSIONS: The transscleral fixation of a posterior chamber intraocular lens has been performed in combination with a vitrectomy in order to minimize postoperative complications. Especially in combination with a pars-plana vitrectomy and silicone oil filing the transsclerally fixated posterior chamber intraocular lens is superior to the anterior chamber IOLs.

Follow-Up Studies↗

Apical and basal regulation of the permeability of the retinal pigment epithelium.

PURPOSE: The functional characteristics of tight junctions in the outer blood-retinal barrier change during embryonic development and in the presence of disease. A culture model of developing retinal pigment epithelium (RPE) was used to examine the regulation of the tight junctions. METHODS: RPE from chick embryos was cultured on filters that separated the apical and basal medium compartments. Cultures were maintained in various combinations of serum-free medium, serum-free medium that was conditioned by neural retinas, or serum-free medium that was supplemented with bovine pituitary extract, serum, or various hormones. Function was monitored by the transepithelial electrical resistance (TER) or the permeation of small organic tracers. Structure was monitored by immunofluorescence and freeze-fracture electron microscopy. RESULTS: Functional analysis indicated differences in permeability among RPE of different embryonic age and culture conditions. In serum-free medium, the tight junctions were leaky or failed to form. Barrier properties increased if pituitary extract was added to the basal medium chamber or retina-conditioned medium was added to the apical chamber. Retina-conditioned medium was more effective at organizing tight junctional strands into a continuous network, but bovine pituitary extract appeared to modulate the permeability of that network. In combination, they synergistically elevated the TER to physiological levels. Although the thyroid hormone T3 had no effect, serum in the apical medium chamber inhibited the ability of RPE cells to respond to retina-conditioned medium. CONCLUSIONS: Diffusible factors secreted by the neural retina acted synergistically with basolateral stimulation to regulate the structure and function of RPE tight junctions. Serum on the apical side of the RPE monolayer inhibited the ability of retinal factors to upregulate the tight junction barrier.

Animals↗

[Vitreous involvement in cytomegalovirus retinitis].

In our outpatient department we often see patients with vitreous inflammation. Recent reports emphasize that vitreous inflammation is very rare, so we looked for patients with cytomegalovirus (CMV) retinitis and vitreous inflammation. We investigated 359 HIV-positive patients for at least 1 year; all patients reached the stage of AIDS disease. We included patients without any retinal signs of CMV retinitis at the beginning or CMV recurrence during the study. A slit-lamp investigation, binocular funduscopy and b-picture ultrasound were done at regular intervals. The results show an increase in vitreous inflammation with the frequency of CMV retinitis recurrences. Patients very often develop retinal detachment. Vitreous inflammation is a critical factor when examining CMV retinitis. In the future a larger series of patients should be examined.

AIDS-Related Opportunistic Infections↗

Developmental analysis of the cone photoreceptor-less little skate retina reveals distinct Onecut1 isoforms.

The retinal development of elasmobranchs, the subclass comprising sharks, skates, and rays, remains poorly understood. This group is diverse in retinal phenotype, with many sharks and rays possessing rods together with one or more cone types. In contrast, the little skate (Leucoraja erinacea) has only a single rod photoreceptor type, which has been reported to exhibit some physiological and anatomical properties associated with cones. To investigate how this unusual photoreceptor system develops, we first identified an embryonic stage of early photoreceptor formation based on otx2 expression. We then developed a retinal electroporation approach to test whether a onecut1-dependent cone-associated reporter could be activated in the embryonic skate retina. Activation of this reporter was not detected, indicating that the corresponding enhancer is not robustly active under the conditions tested. To assess developmental changes in gene expression, we generated bulk RNA-seq datasets from embryonic, hatchling, and adult retinas. These analyses showed strong embryonic expression of onecut1, increasing expression of rod-associated genes through development, and pseudogenization or loss of multiple cone-enriched genes. We further identified a developmentally regulated onecut1 splice isoform containing an additional 48 amino acid sequence between the CUT and homeodomain DNA-binding domains. This spacer-containing isoform, termed LSOC1X2, was most abundant in the embryonic retina. To test whether LSOC1X2 retained regulatory activity, we assayed it in a mouse retinal reporter system. Both skate Onecut1 isoforms activated the ThrbCRM1 reporter in this heterologous context. Together, these findings identify a novel, developmentally regulated retinal onecut1 isoform in the little skate and establish it as a candidate regulator for future studies of photoreceptor development in this species and its elasmobranch relatives.

Animals↗

Expression of Bcl-2 during the development of rabbit retina.

AIM: Programmed cell death or apoptosis plays an important role in retinal development. Bcl-2 is one of the genes whose endproducts regulate apoptosis. This study has examined the expression of Bcl-2 during the development of rabbit retina. METHOD: Bcl-2 was detected by immunohistochemistry in developing rabbit retinas from embryonic day (E) 15, 22, 26, 29 and postnatal day (PN) 0, 3, 7, 15 and adults. RESULTS: Faint immunoreactivity in the anuclear layer was observed at E 15, which increased in E 19. Immunoreactivity in certain radially aligned neuroepithelial cells/immature Müller cells could be recognized at E 22 and it progressively increased until in mature Müller cells radial processes were immunoreactive beyond the outer plexiform layer in PN 15 retinas. Immunoreactivity was already present in the optic nerve at E 15 but it decreased with increasing age until it disappeared at the time of birth. CONCLUSIONS: Observations suggest that Bcl-2 is transiently expressed by ganglion cell axons during embryonic development. Detection of Bcl-2 immunoreactivity in the endfeet and proximal processes of radially aligned neuroepithelial cells/immature Müller cells early during the development, and its persistence in the endfeet and much of radial processes of Müller cells in adult life suggest that these cells possibly play a role in the development of the retinal ganglion cells, and also in the maintenance of the retinal neurons in the adults.

Animals↗

Rapid spread of a neurovirulent strain of HSV-1 through the CNS of BALB/c mice following anterior chamber inoculation.

Following uniocular anterior chamber (AC) inoculation of BALB/c mice with the KOS strain of herpes simplex virus type 1 (HSV-1), virus spreads from the injected eye to the ipsilateral suprachiasmatic nucleus (SCN) in the central nervous system (CNS) to infect the optic nerve and retina of the contralateral eye, and mice develop retinitis in that eye only. In contrast, after AC inoculation of BALB/c mice with the H129 strain of HSV-1, mice develop bilateral retinitis. The pathway(s) by which H129 spreads to cause bilateral retinitis is not known. To determine the route and timing of H129 spread after AC inoculation, BALB/c mice were injected in the AC of the right eye with 5 x 10(3) PFU of H129. Brains from 30 mice were sectioned on a brain matrix and the amount of virus in the brain and eyes was determined by plaque assay. Frozen sections were prepared from the eyes, brain, and trigeminal ganglia of an additional 30 mice, and HSV-1 antigen was detected by immunohistochemistry. After AC inoculation, H129 follows a pathway similar to KOS in the CNS, but H129 appears to spread more rapidly than KOS within the CNS. Unlike KOS, H129 is able to infect brain stem nuclei and H129-infected mice developed neurological impairments in addition to bilateral retinitis. The results of these studies suggest that the ability of H129 to spread rapidly in the CNS allows early virus infection of retino-recipient nuclei proximal to the contralateral and ipsilateral optic nerves. Early infection of retino-recipient nuclei, such as the SCN may allow virus to spread into the retinas before a virus-specific immune response can be induced.

Animals↗

Structure of clonal and polyclonal cell arrays in chimeric mouse retina.

One of the most striking results of recent cell-lineage studies of vertebrate retina is the marked variability in the size and types of clones marked by retroviral transfection and dye injection of embryonic progenitor cells. Is this variability due to microenvironmental modulation of cell determination, to lineage restriction, or to experimental perturbation of the progenitor cells? We have taken advantage of species-specific DNA probes to mark groups of lineage-related cells in experimental mouse chimeras. This method of marking cells has two distinct advantages over previous methods: direct manipulation of progenitor cells is avoided, and clones are established at an earlier stage of retinal development. The most notable feature of retinal cohorts in chimeras is their structural uniformity--each is a solid radial array that contains the same ratio of major cell types as the retina itself. This is true even of the smallest monoclonal cohorts, which contain fewer than 200 cells. Our results provides compelling empirical support for the hypothesis that the murine retina is made up of hundreds of relatively homogeneous radial units, each derived from single retinal precursor cells. This finding is inconsistent with micro-environmental modulation of clone structure early in development. We raise the possibility that the heterogeneity among clones marked by dye injection and transfection is due to progressive lineage restriction or to experimental perturbation of the retinal progenitor cells.

Animals↗

Development of the retinal pathway to the pretectum of the cat.

The development of retinal projections to the pretectal complex of prenatal and early postnatal cats has been examined using the anterograde transport of horseradish peroxidase and tritiated amino acids. As early as embryonic day 38, the entire dorsal pretectum is penetrated by retinal ganglion cell axons. At this stage the bilateral complement of retinal efferents appears to be dispersed uniformly within the pretectal anlage. A week later, on embryonic day 46, indistinct foci of peroxidase reaction product can be discerned within 2 of the primordial nuclei: the nucleus of the optic tract and the olivary nucleus. By embryonic day 56, five distinct bilateral fields of retinal fiber termination are apparent within the following regions: (i) the nucleus of the optic tract; (ii) the pretectal olivary nucleus; (iii) the posterior pretectal nucleus; (iv) the anterior pretectal nucleus; and (v) the medial pretectal nucleus. Four days before birth, on embryonic day 61, crossed and uncrossed retinal arbors are partially segregated within the nucleus of the optic tract and the pretectal olivary nucleus. The early postnatal retinal connection to the pretectum has an overall pattern virtually indistinguishable from that of the mature cat. The ontogeny of the retinal influx to the pretectum is similar to that of the retinocollicular projection. However, the development of retinal projections to the pretectum and superior colliculus appears to lag behind those to the dorsal lateral geniculate nucleus. These differences may reflect temporal and spatial gradients in the maturation of three major classes of retinal ganglion cells.

Animals↗

Qualitative and quantitative measures of plasticity during the normal development of the Rana pipiens retinotectal projection.

We have examined the following aspects of retinal development in the frog, Rana pipiens: (1) the overall pattern of cell addition to the retina; (2) the relative rate of retinal ganglion cell (RGC) accretion; and (3) the changes in RGC density during larval development. In addition, we have studied the development of the retinal projection onto the tectum by means of the anterograde transport of horseradish peroxidase (HRP) and measurements of the volume of tectal neuropil at several larval stages and in postmetamorphic frogs. We find that the addition of new cells to the retina of Rana pipiens larva is restricted to the ciliary margin and that this addition is concentric at all larval stages. Additionally, the morphometric measures of retinal and tectal growth, along with the HRP histochemistry, indicate that the retinal projection exhibits considerable plasticity during normal development. The plasticity we observe in normal development may explain why the retinotectal projection can compensate its area and volume in experimental paradigms that effect drastic changes in innervation density.

Animals↗

Intravitreal ganciclovir treatment in progressive outer retinal necrosis.

PURPOSE: To report two patients with progressive outer retinal necrosis, which is presumed to be caused by the varicella-zoster virus in patients with acquired immunodeficiency syndrome (AIDS). METHOD: Case report. RESULTS: The patients were treated with intravenous foscarnet, 60 mg per kg of body weight three times per week, without response. Remission of retinal necrosis occurred with the commencement of intravitreal ganciclovir treatment, 400 mg two times per week. Laser photocoagulation was performed in both cases. Neither patient developed retinal detachment. CONCLUSIONS: Intravitreal ganciclovir treatment combined with systemic antiviral agent therapy in patients with progressive outer retinal necrosis may delay progress of the disease. Early photocoagulation may prevent the development of retinal detachment if retinal necrosis is controlled.

AIDS-Related Opportunistic Infections↗

A simple method for screening photoelectric dyes towards their use for retinal prostheses.

Photoelectric dyes absorb light and convert photon energy to electric potentials. To test whether these dyes could be used for retinal prostheses, a simple in vitro screening system was developed. Retinal neurons were cultured from the eyes of chick embryos at the 10-day embryonic stage, at which time no retinal photoreceptor cells have yet developed. Intracellular calcium elevation was observed with Fluo-4 in cultured retinal neurons before and after photoelectric dye was applied at varying concentrations to the culture medium. Five of 7 photoelectric dyes tested in this in vitro system induced intracellular calcium elevation in cultured chick retinal neurons. The intracellular calcium elevation generated by the 5 photoelectric dyes was blocked by extracellular calcium depletion in the case of all 5 dyes, and, except for one dye, by the presence of voltage-gated calcium channel blockers. The photoelectric dyes absorbed light under an inverted microscope and stimulated retinal neurons. This simple in vitro system allows the screening of photoelectric dyes which can be used for retinal prostheses.

Animals↗

Retinal detachment caused by retinal dialysis.

PURPOSE: To determine the characteristics of patients developing retinal detachment secondary to retinal dialysis in Western Australia and to confirm the clinical impression that these patients had a low rate of proliferative vitreoretinopathy (PVR). METHODS: A retrospective analysis of the records of 1601 consecutive patients with rhegmatogenous retinal detachment identified 71 patients in whom the retinal detachment was caused by a retinal dialysis. RESULTS: The majority of these patients were young adults (mean age of 30 years) and the male to female ratio was 1.3:1. Seventy per cent of patients provided a history of significant trauma to the affected eye. Sporting injuries, assault, and motor vehicle injuries together accounted for 72% of identifiable trauma. Examination revealed a dialysis of the inferotemporal quadrant in 75% of cases and despite obvious signs of chronicity of the associated retinal detachment (such as intraretinal macrocysts and demarcation lines) in approximately one-third of the eyes, only 5.6% developed grade CI PVR either pre- or postoperatively. CONCLUSION: The present study supports the view that it is the low rate of PVR that explains the good prognosis and high surgical success rate for retinal detachments caused by retinal dialysis. It is postulated that a major reason for the low rate of PVR is that the vitreous base attachment to the posterior margin of a retinal dialysis acts as a significant barrier to the migration of potentially proliferative retinal pigment epithelial cells. This may lead to containment of the responsible proliferative cells within the loculated subretinal space.

Adolescent↗

Organization and development of horizontal cells in the goldfish retina, I: The use of monoclonal antibody AT101.

We have produced and characterized a monoclonal antibody, AT101, which selectively labels both viable and formaldehyde-fixed horizontal cell axon terminals, but not their somas or axons, of the goldfish (Carassius auratus) retina. The antigen recognized by AT101 appears to be a cell surface glycoprotein with a molecular weight of about 35,000 Daltons, and is present exclusively or predominantly in nervous tissues of all vertebrate species examined. We have used AT101 as a probe to analyze immunocytochemically the organization of horizontal cell axon terminals (HCATs) in the adult goldfish retina, and the emergence and maturation of these terminals during retinal development. Because of continued growth at the retinal margin in adult goldfish, there is a peripheral-to-central gradient in the age of cells, with the most mature in the center and the youngest in the periphery. In the center and near periphery of the adult retina, HCATs have a fusiform morphology and form a dense network in the middle and proximal part of the inner nuclear layer. In the far peripheral retina, the axon terminals appear round or ellipsoid. The retina closest to the retinal margin is devoid of AT101 staining, indicating that either HCATs are absent or the antigen recognized by AT101 is not present on HCATs at this stage. A similar sequence of changes in staining pattern is seen during development. Although AT101 staining can first be demonstrated in the larval retina at 1 month after hatching, it appears mostly as punctate structures. At a later stage, there are round or ellipsoid structures that resemble in morphology and location (in the inner nuclear layer) those found in the far peripheral adult retina. Double-labeling experiments with AT101 and antiserum against tubulin also indicate that AT101 labels the HCATs when they first appear during development. These data suggest that the emergence and maturation of HCAT is a late event in retinal development.

Animals↗

Effects of Müller cell disruption on mouse photoreceptor cell development.

Müller cells have been proposed to play an important role in photoreceptor cell development during the final stages of retinal maturation. The effect of disrupting Müller cells during mouse retinal development was investigated using the specific glial cell toxin, DL-alpha-aminoadipic acid (AAA). By giving multiple systemic injections over several days, impairment of Müller cell function was maintained during the period of photoreceptor migration and differentiation. Following three consecutive days of AAA treatment [commencing on post-natal (P) day 3, 5, 7 or 9, and examined at P8-P14], clumps of photoreceptor nuclei were displaced through the inner segments, lying immediately beneath the retinal pigment epithelium (RPE). Apart from the scalloped appearance of the outer retina, the overall lamination pattern of the retina was relatively well preserved. Even when AAA treatment commenced as early as P3, several days prior to the formation of the outer nuclear layer, the majority of photoreceptors migrated to their correct position and formed inner and outer segments. Therefore, the signals for photoreceptor migration are either provided by the Müller cells prior to P3, or, alternatively, are derived from different intrinsic or extrinsic cues. Disruption of Müller cell function was evidenced by decreased glutamine synthetase activity as well as by increased glial fibrillary acidic protein (GFAP) and decreased cellular retinaldehyde-binding protein (CRALBP) immunoreactivity. Immunocytochemistry with an antibody to CD44, which labels the microvilli of Müller cells at the outer limiting membrane, coupled with electron microscopic analysis, demonstrated that the zonulae adherentes between Müller cells and photoreceptors were either irregular or absent in areas adjacent to displaced clumps of photoreceptors. Thus AAA treatment of early post-natal mice results in localized disruption of the contacts between Müller cells and photoreceptors. These pathologic changes persist into adulthood since at P28, while short stretches of photoreceptors appeared relatively normal with fully developed outer segments, periodic clumps of displaced photoreceptor nuclei were still present adjacent to the RPE. In conclusion, Müller cell processes at the outer limiting membrane appear to play a critical role in providing a barrier to aberrant photoreceptor migration into the subretinal space.

2-Aminoadipic Acid↗

PVR recurrence and the timing of silicon oil removal.

BACKGROUND: Following vitrectomy for PVR-associated retinal detachment, placement of an encircling band, filling with silicone oil (SO) and successful retinal reattachment, a recurrence of PVR can develop. Retinal redetachment after SO removal is usually due to secondary or residual PVR. We wanted to ascertain whether the anatomical and functional outcomes of surgery in patients with a reattached retina and recurrent PVR can be improved by delaying the removal of SO. PATIENTS AND METHODS: 112 consecutive patients with PVR-associated retinal detachment who had undergone vitrectomy with SO filling, were monitored for at least 6 months after SO removal. Prior to SO removal, the retina posterior to the encircling band had to be completely reattached. Patients who developed PVR after SO filling were divided into two groups according to the duration of SO retention: 12 - 18 months (group 2: n = 48); > 18 months (group 3: n = 21). Individuals without PVR recurrence after SO filling and in whom the SO was consequently removed within 4 - 12 months served as control (group 1: n = 43). Anatomical success, intraocular pressure (IOP) and best-corrected visual acuity (BCVA) served as the primary clinical outcome parameters. RESULTS: Six months after SO removal, the anatomical success rates (86.3 %, 88.8 % and 84.6 %, in groups 1, 2 and 3, respectively; log rank = 0.794) and the BCVAs (p = 0.861) were comparable in the three groups. Mean IOP (p = 0.766), and the frequency of complications such as PVR recurrence (p = 0.936), bullous keratopathy (p = 0.981) and macular pucker (p = 0.943) were likewise similar. Patients in whom SO was retained for more than 18 months had the highest IOPs and required the heaviest dosage with anti-glaucoma drugs. CONCLUSIONS: In patients who develop a recurrence of PVR after vitrectomy and SO filling the surgeon can observe and treat retinal changes for up to 18 months without impairing the anatomical and functional outcomes. The retention of SO for more than 18 months does not improve the anatomical outcome. However, it can impair the functional outcome by precipitating the development of a persisting secondary glaucoma.

Comorbidity↗

Failure of prophylactic retinopexy in fellow eyes without a posterior vitreous detachment.

OBJECTIVE: To describe adverse sequelae of retinal prophylaxis in fellow eyes of patients with rhegmatogenous retinal detachment. DESIGN: Records were reviewed for 17 patients who had retinal breaks or detachment subsequent to prophylactic retinopexy applied to the fellow eye (without posterior vitreous detachment) at the time of primary rhegmatogenous retinal detachment surgery. Subsequent treatment included cryotherapeutic and laser retinopexy, scleral buckling, and vitrectomy. RESULTS: Of the 17 patients, 12 were male (mean age, 49 years). Laser retinopexy alone was used in 6 cases. Sixteen (94%) developed retinal tears related to acute posterior vitreous detachment, of which 8 (47%) were at the edge of retinopexy and 8 (47%) were in the normal or untreated retina. Thirteen (76%) developed a retinal detachment, of which 11 (85%) did not involve the fovea. Median visual acuity following treatment was 0.18 logMAR (6/9 Snellen equivalent). CONCLUSIONS: Prophylactic retinopexy in fellow eyes without posterior detachment is not completely successful and may cause breaks to develop at the edge of treated areas during subsequent acute posterior vitreous detachment. Patient education alone regarding the symptoms of retinal tear and detachment may be preferable to prophylactic retinopexy of the fellow eye in the absence of a posterior vitreous detachment.

Adolescent↗

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 1 840 000, 192 residents developed retinal detachment. The annual incidence was therefore 10.4 per 100 000 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 100 000 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.

Adolescent↗

Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage.

Transgenic mice carrying the murine granulocyte-macrophage colony stimulating factor (GM-CSF) gene expressed from a retroviral promoter exhibit elevated levels of GM-CSF in the serum, urine, peritoneal cavity, and eye. The eyes of transgenic mice are opaque, contain accumulations of macrophages, and develop retinal damage. Similarly, lesions containing macrophages develop in striated muscle. The mice also display an accumulation of large, often multinucleate, activated macrophages in the peritoneal and pleural cavities. The transgene is transcribed in peritoneal cells, as well as in eyes and infiltrated striated muscle. A high proportion of transgenic mice die with muscle wasting when aged 2-4 months, possibly because of macrophage activation resulting from the high levels of GM-CSF.

Animals↗