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[Planimetric follow-up of cytomegalovirus retinitis treated with ganciclovir in patients with AIDS].

In 28 cases of cytomegalovirus retinitis being treated with ganciclovir we examined the relative value of planimetry and conventional investigative methods, such as visual field examination and serial fundus photographs in determination of the development of retinitis. Planimetric evaluation was not possible in 11 of the 28 cases because of technical problems inherent in the method. In 17 cases we found no correlation between visual acuity, visual field and area of retinal necrosis evaluated by planimetry. This shows the low value of visual acuity tests and planimetric evaluation of routine fundus photographs in the examination of the development of common retinitis. In selected cases with primary visual acuity of less than 1/10 (e.g., in optic nerve involvement) the planimetry of fundus photographs seems to yield more information than the standard ophthalmological routine examinations.

Acquired Immunodeficiency Syndrome↗

Rhegmatogenous retinal detachment after LASIK for myopia.

PURPOSE: To report the characteristics and incidence of rhegmatogenous retinal detachment in myopic eyes after LASIK. METHODS: The medical records of 49 patients with rhegmatogenous retinal detachment after LASIK were reviewed. The incidence of rhegmatogenous retinal detachment after LASIK was determined and potential risk factors were evaluated. RESULTS: LASIK was performed on 59,424 eyes with spherical equivalent refraction (SE) ranging from -0.75 to -26.50 diopters (D) (mean: -6.10 +/- 3.5 D). Forty-nine eyes developed rhegmatogenous retinal detachment between 1.5 and 76 months (mean: 27.3 +/- 21.7 months) after LASIK. The mean preoperative refractive error in these eyes was -8.6 +/- 3.9 D. Mean age of these patients was 38.2 +/- 11.2 years. Thirty-five (71.4%) patients were male. The cumulative incidence of rhegmatogenous retinal detachment was 0.082% (95% confidence interval [CI]: 0.061-0.109), and the yearly incidence was 0.032% (95% CI: 0.023-0.042) after LASIK. The most frequent location of the retinal breaks was the superior temporal quadrant (22.7%). Male sex, older age, and higher preoperative myopia were significantly related to the incidence of rhegmatogenous retinal detachment after LASIK (P<.001). CONCLUSIONS: Based on the results of this study, following the treatment of high-risk peripheral retinal lesions, LASIK did not appear to be an additional risk factor for the development of rhegmatogenous retinal detachment after LASIK in our patients; however, patients should be informed of the possibility of this complication as a consequence of myopia. Patients who are male, older in age, and have high myopia preoperatively may be at increased risk.

Adolescent↗

Rhegmatogenous retinal detachment after rupture of retinal arterial macroaneurysm.

PURPOSE: To report two cases of rhegmatogenous retinal detachment following rupture of retinal arterial macroaneurysm. DESIGN: Observational case report. METHODS: Review of clinical records of 75 consecutive eyes (73 patients) with macroaneurysm. RESULTS: Ruptured macroaneurysm was present in 68 of the 75 eyes, and rhegmatogenous retinal detachment developed spontaneously in 2 (2.9%) of the 68 eyes. In the 2 eyes with retinal detachment, there were no predisposing lesions to retinal detachment and the detachment occurred either 2 weeks or 1 month after the rupture of a macroaneurysm. Retinal detachment and posterior vitreous detachment developed simultaneously after bleeding from the macroaneurysm spread into the vitreous in 1 eye. CONCLUSIONS: We report the occurrence of retinal detachment after macroaneurysmal rupture. Detailed fun-dus examination is required to detect retinal detachment in the follow-up of patients with ruptured macroaneurysm.

Aged↗

K+ Channel density increases selectively in the endfoot of retinal glial cells during development of Rana catesbiana.

The radial glial cells that span the retina, described by Müller in 1851, have a remarkable distribution of ion channels in adult amphibia that mediate extracellular K+ spatial buffering. 94% of the total membrane conductance of these cells resides in inward rectifier K+ channels in the endfoot processes apposed to the vitreous humour. We now report that this regional specialization is found in Müller cells isolated from adult (>120 day old) bullfrogs but to a far less extent in those from 10-20 day old tadpoles (stages 34-36). Using the cell attached configuration of the patch-clamp technique, we found, in agreement with previous studies in salamanders, that the endfoot of adult cells had 19.2+/-2.4 (mean +/- S.E., n = 81) channels/patch, whereas the soma had 1.81+/-0.28 (n = 21) channels/patch. In the tadpole, the respective values were 4.29+/-0.26 (n = 79) for the endfoot and 2.26+/-0.24 (n = 27) for the soma. The slope conductance of the inward rectifier K+ channel in 115 mM K+, 19.2+/-0.25 pS (n = 205), channel kinetics and the resting membrane potential (-69+/-2.7 mV, n = 224) were similar at both the endfoot and soma of both adults and embryos. We conclude that during development, the K+ conductance of the Müller cell endfoot, but not of the soma, increases due to a selective clustering of inwardly rectifying K+ channels in that specific region of the cell membrane. The properties of the channels change little during the transformation from tadpole to adult bullfrog.

Animals↗

Retinal synaptic arrays: continuing development in the adult goldfish.

We report a light- and electron-microscopic examination of the inner plexiform layer of the central retina of young (c. 1 year) and old (3-4 year) goldfish. There were no new neurons added to this region during the growth period. Nonetheless, there were substantially more synapses (per cell, per mm2, or per degree 2) in the older retinas. This result is discussed in the contexts of retina function and neural development.

Animals↗

Protein gene product 9.5-immunoreactive retinal neurons in normal developing rats and rats with optic nerve or tract lesion.

The present immunocytochemical study indicates that protein gene product 9.5 (PGP 9.5) in the rat retina first appears in a population of neurons in the inner and central part of the neuroblast layer at embryonic day (E) 14. Presumptive horizontal cells which are PGP 9.5 positive were observed at E17. At birth, cells in the inner nuclear layer and ganglion cell layer (GCL) as well as the inner plexiform layer (IPL) were positive. Further differentiation, particularly the appearance and the formation of immunoreactive sublaminae in the IPL, was observed in the first 2 postnatal weeks. This pattern reached adult levels by postnatal day 14. In rats with unilateral neonatal optic tract lesion or optic nerve transection as young adults, 43-45% of the immunoreactive cells were lost in the GCL. However, only minor changes were detected in the IPL, suggesting that amacrine cells contribute mainly to the PGP 9.5 immunoreactivity in this laminar zone of the retina.

Aging↗

RPE65 gene mutation prevents development of autofluorescence in retinal pigment epithelial phagosomes.

During senescence, autofluorescent lysosomal storage bodies known as lipofusin or age pigment accumulate in many post-mitotic types of cells. Among these cell types is the retinal pigment epithelium (RPE) of the mammalian eye. The mechanisms of lipofuscin formation and accumulation have been studied more extensively in the RPE than in any other cell type. Substantial evidence indicates that Vitamin A derivatives (retinoids) are required for RPE lipofuscin formation. The RPE and adjacent retina contain retinoids in the forms of retinol, retinyl esters, and retinaldehyde. Previous research has demonstrated that retinaldehydes are directly involved in the formation of one RPE lipofuscin fluorophore. However, RPE lipofuscin contains many other fluorophores. It has not been determined which retinoids are involved in the formation of these fluorescent compounds. Mice with a mutation in the Rpe65 gene contain substantial levels of retinol and retinyl esters in the RPE, but little if any retinaldehydes in either the RPE or retina. Therefore, these mice could be used to determine whether retinaldehydes are required for formation of all of the RPE lipofuscin fluorophores. Normal mice were given intraocular injections of a protease inhibitor, which resulted in the rapid accumulation in the RPE of lipofuscin-like inclusions. These inclusions exhibited fluorescence properties typical of RPE lipofuscin. Rpe65-/- mice treated with the protease inhibitor also accumulated inclusions similar to those observed in the normal mice. However, these inclusions did not fluoresce under the conditions used to visualize lipofuscin fluorescence. These findings indicate that the aldehyde form of Vitamin A is required for the formation of not only one, but all of the RPE lipofuscin fluorophores.

Aging↗

Physiologic diversity and development of intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate numerous nonvisual phenomena, including entrainment of the circadian clock to light-dark cycles, pupillary light responsiveness, and light-regulated hormone release. We have applied multielectrode array recording to characterize murine ipRGCs. We find that all ipRGC photosensitivity is melanopsin dependent. At least three populations of ipRGCs are present in the postnatal day 8 (P8) murine retina: slow onset, sensitive, fast off (type I); slow onset, insensitive, slow off (type II); and rapid onset, sensitive, very slow off (type III). Recordings from adult rd/rd retinas reveal cells comparable to postnatal types II and III. Recordings from early postnatal retinas demonstrate intrinsic light responses from P0. Early light responses are transient and insensitive but by P6 show increased photosensitivity and persistence. These results demonstrate that ipRGCs are the first light-sensitive cells in the retina and suggest previously unappreciated diversity in this cell population.

Action Potentials↗

Pax6 is required for delta-catenin/neurojugin expression during retinal, cerebellar and cortical development in mice.

The transcription factor Pax6 regulates multiple aspects of central nervous system (CNS) development. At the cellular level, the Pax6 mutation was reported to affect homophilic and heterophilic cellular adhesion, neuron polarity and neurite outgrowth. These abnormalities were observed in multiple regions of Pax6-mutant CNS, suggesting a common function for Pax6 in regulating cytoskeletal dynamics. However, target genes mediating Pax6 function in cytoskeletal dynamics remain largely unknown. Using DNA microarrays, we identified delta-catenin (delta-catenin /neurojugin) as a potential direct target of Pax6 in the CNS. delta-catenin encodes a large cytoskeletal protein that localizes at adherens junction in the CNS and that can modulate neurite outgrowth and N-cadherin turnover. delta-catenin was found to be co-expressed with Pax6 in several regions of the developing CNS. In Pax6 mutant embryos, delta-catenin expression was severely reduced in the optic vesicle neural ectoderm, in the ventricular zone of the neocortex and in the external granule layer of the cerebellum. We identified a Pax6 binding site in delta-catenin promoter that is conserved between mice and humans and which is effectively bound by Pax6 in vitro. Our results suggest that Pax6 regulates delta-catenin expression during CNS development in mice.

Animals↗

Tomographic findings of foveal hard exudates in diabetic macular edema.

PURPOSE: To report the intraretinal location of foveal hard exudates after vitrectomy to treat diabetic macular edema and to evaluate the visual outcome. METHODS: In a prospective study, the tomographic features of 11 eyes (8 patients) with diabetic macular edema were evaluated with optical coherence tomography after vitrectomy. The intraretinal location of hard exudates at the fovea (anatomic foveola) and the relationship with visual acuity were investigated. RESULTS: With optical coherence tomography, hard exudates were observed as highly reflective spots in the cross-sectional images. In six of 11 eyes (54.5%), the hard exudates were in the inner portion of the neurosensory retina; the final best-corrected visual acuity averaged 20/70 in the six eyes. In the remaining five eyes (45.5%), hard exudates were deposited not only in the neurosensory retina but also in the subretinal space. In optical coherence tomographic images, subretinal hard exudates were observed as highly reflective plaques, which were slightly elevated over the retinal pigment epithelium. The five eyes developed a serous retinal detachment at the fovea before or after vitrectomy. Subretinal hard exudates bridged the detached neurosensory retina and the retinal pigment epithelium in two eyes. The average final visual acuity level in the five eyes was 20/300. The visual outcome was significantly worse in five eyes with subretinal hard exudates than in six eyes with an intraretinal one (P <.05, Wilcoxon rank sum tests). CONCLUSIONS: If serous retinal detachment develops before or after vitrectomy for diabetic macular edema, hard exudates tend to accumulate not only in the neurosensory retina but also in the subretinal space. The visual prognosis is worse in cases of subretinal exudation.

Aged↗

Retinal detachment in phakic eyes with anterior chamber intraocular lenses to correct severe myopia.

PURPOSE: To analyze the incidence and characteristics of retinal detachment in patients with severe myopia corrected by implantation of phakic anterior chamber intraocular lenses. METHODS: We studied retinal detachments in 166 consecutive eyes (98 patients) that underwent implantation of angle-supported phakic anterior chamber intraocular lenses (models ZB5M and ZB5MF; Domilens; Lyon, France) for the correction of severe myopia (follow-up +/- SD, 45.26 +/- 14.65 months; range, 20 to 84 months). RESULTS: Retinal detachment occurred in eight eyes (4.8%); four eyes belonged to men and four to women. The time between implanting surgery and retinal detachment was 17.43 +/- 16.4 months (range, 1 to 44 months). In all cases, retinal detachment was spontaneous. In seven eyes, the retina was reattached successfully during the first retinal detachment surgery. Mean best-corrected visual acuity after phakic anterior chamber intraocular lens implantation and before retinal detachment development was 20/50 (range, 20/100 to 20/25). After retinal detachment repair, best-corrected visual acuity was 20/73 (range, 20/2000 to 20/33). In these seven eyes, differences between best-corrected visual acuity before and after reattachment were not statistically significant (P = .898, paired Student t test). In one eye, a proliferative vitreoretinopathy was observed, which required additional treatment by vitrectomy and explantation of the phakic anterior chamber intraocular lens. A refractive change was observed after retinal detachment repair, from -1.1 +/- 0.7 diopters (range, 0.00 to -2.50 diopters) before retinal detachment and -2.8 +/- 1.1 diopters (range, -1.00 to -4.50 diopters) after retinal detachment surgery (P = .03, paired Student t test). CONCLUSIONS: The implantation of a phakic anterior chamber intraocular lens as a correcting procedure for severe myopia was followed by a 4.8% incidence of retinal detachment. Conventional scleral surgery was successful in most cases, without causing significant changes in the final best-corrected visual acuity. A significant increase in the myopic spherical equivalent was observed after retinal detachment repair in these patients.

Adult↗

Glial cells mediate target layer selection of retinal axons in the developing visual system of Drosophila.

In the fly visual system, each class of photoreceptor neurons (R cells) projects to a different synaptic layer in the brain. R1-R6 axons terminate in the lamina, while R7 and R8 axons pass through the lamina and stop in the medulla. As R cell axons enter the lamina, they encounter both glial cells and neurons. The cellular requirement for R1-R6 targeting was determined using loss-of-function mutations affecting different cell types in the lamina. nonstop (encoding a ubiquitin-specific protease) is required for glial cell development and hedgehog for neuronal development. Removal of glial cells but not neurons disrupts R1-R6 targeting. We propose that glial cells provide the initial stop signal promoting growth cone termination in the lamina. These findings uncover a novel function for neuron-glial interactions in regulating target specificity.

Amino Acid Sequence↗

Stimulation of the retina with a multielectrode extraocular visual prosthesis.

BACKGROUND: An extraocular approach to developing a retinal prosthesis for blind patients using electrodes placed on the outer surface of the eye is suggested. Experiments were carried out to determine the feasibility of this approach, and evaluate electrode configurations and parameters for stimulation. METHODS: In anaesthetized cats, a 21-electrode extraocular retinal prosthesis (ERP) array was sutured to the sclera over the lateral surface of the eye. Electrically evoked potentials (EEP) were recorded at the visual cortex bilaterally in response to retinal stimulation with the electrode array. Bipolar stimulation of the ERP array electrodes in horizontal and vertical configurations and at different interelectrode separations was investigated with biphasic constant-current pulses. RESULTS: Electrical stimulation of the lateral retina with an ERP elicited EEP that were higher in the ipsilateral visual cortex. The threshold for bipolar retinal stimulation was 500 microA. EEP amplitude increased with increases in stimulus pulse duration and current intensity. Retinal stimulation was slightly more effective with electrodes in a vertical as opposed to horizontal orientation. A larger interelectrode separation resulted in a higher EEP amplitude. CONCLUSIONS: Retinal stimulation with a prototype ERP array is demonstrated. The thresholds for retinal excitation are below safe charge-density limits for chronic neural stimulation. Ipsilateral localization of the EEP suggests that localized retinal stimulation is occurring. An ERP is a new approach to retinal prosthesis research, and might lead to the development of a low-resolution visual prosthesis for blind patients.

Animals↗