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Retinal detachment in patients with acquired immunodeficiency syndrome.

Cytomegalovirus retinopathy is the most frequent opportunistic infection of the eye in patients with acquired immunodeficiency syndrome (AIDS). We studied 71 patients with cytomegalovirus retinopathy (n = 69) or acute retinal necrosis (n = 2) with respect to the frequency and management of retinal detachment. Retinal detachment was seen in 14 patients (relative frequency, 19.7%). In 2 patients, the retinal detachment was bilateral. In 5 patients, pars plana vitrectomy and silicone-oil tamponade was performed, and in 1 of these patients scleral buckling was applied before vitrectomy. In 3 other patients scleral buckling was performed, and 1 of these individuals had sulfur-hexafluoride injection. In 8 eyes (6 patients), retinal detachment occurred in eyes with completely burned-out retinopathy without relevant function, and no surgical treatment was performed. Long-term retinal reattachment was seen in all 5 patients undergoing pars plana vitrectomy with silicone-oil tamponade. Visual acuity was preserved until the last follow-up in 4 of these 5 patients. In the patients undergoing a buckling procedure alone, no anatomic or functional success was observed. During vitrectomy, reduced retinal vascular perfusion and blood-flow sludging was observed in 2 patients. As the duration of survival of patients with AIDS and cytomegalovirus retinopathy or acute retinal necrosis is increasing, more cases of retinal detachment will be observed. Overall, 5% of patients with AIDS are expected to develop retinal detachment. In conclusion, treatment of cytomegalovirus-associated retinal detachment by pars plana vitrectomy with silicone-oil tamponade seems to be successful and safe and may maintain the patient's quality of life.

AIDS-Related Opportunistic Infections↗

Spatial and temporal patterns of proliferation and differentiation in the developing turtle eye.

Here we show for the first time different aspects of the pattern of neurogenesis in the developing turtle retina by using different morphological and molecular clues. We show the chronotopographical fashion of occurrence of three major aspects of retinal development: (1) morphogenesis of the optic primordia and emergence of the different retinal layers, (2) the temporal progression of neurogenesis by the cessation of proliferative activity, and (3) the apparition and cellular localization of different antigens and neuroactive substances. Retinal cells were generated in a conserved temporal order with ganglion cells born first, followed by amacrine, photoreceptor, horizontal and bipolar/Müller cells. While eventually expressed in many types of retinal neurons, Islet1 was permanently expressed in differentiating and mature ganglion cells. Calbindin-immunoreactive elements were found in the ganglion cell layer and the inner nuclear layer. Interestingly, at later stages the amount of expressing cells in these layers was reduced dramatically. On the contrary, the number of calbindin-immunoreactive photoreceptors increased as development proceeded. In addition, calretinin expressing cells were prominent in the horizontal cell bodies, and their processes extending into the outer plexiform layer were also strongly labeled. Finally, the synthesis of gamma-aminobutyric acid (GABA) was detected in developing and matured horizontal and amacrine cells. All these maturational features began in the dorso-central area, in a region slightly displaced towards the temporal retina.

Animals↗

Unusual presentation of acute ocular toxoplasmosis.

Two unusual cases of ocular toxoplasmosis are presented. A 24 year old woman developed retinal and optic nerve neovascularization in conjunction with acute ocular toxoplasmosis. The neovascularization regressed with resolution of the inflammation. The possibility of retinal ischemia or inflammation alone as an etiology are discussed. A 19 year old woman developed optic nerve edema and a marked decrease in vision associated with a nasal toxoplasma lesion and a macular star. With resolution of the process, optic atrophy developed but visual acuity returned to normal. Optic nerve edema and atrophy were felt to result from diffuse inflammation, but not from focal involvement in the nerve itself with the organism.

Adult↗

Cytomegalovirus retinitis and low-grade non-Hodgkin's lymphoma: case report and review of the literature.

Patients with non-Hodgkin's lymphoma may develop retinal or choroidal lesions during the course of their disease. New immunosuppressive therapies currently used in reticuloendothelial malignancies have increased the incidence of opportunistic infections in this patient population. The differentiation of lymphomatous infiltration from opportunistic infection as a cause of chorioretinal infiltrates is critical, as the treatments are fundamentally different. We report a case of a patient with non-Hodgkin's lymphoma who developed a chorioretinal infiltrate that was initially thought to represent progressive disease. The patient received radiation treatment appropriate for intraocular lymphoma. The lesion progressed further and after reevaluation a diagnosis of cytomegalovirus retinitis was made and therapy initiated. Review of the literature for intraocular lymphoma and cytomegalovirus retinitis is provided and diagnostic strategies are described. We recommend analysis of intraocular fluid when there is difficulty in clinically differentiating intraocular lymphoma from opportunistic infection.

Antiviral Agents↗

RaxL regulates chick ganglion cell development.

RaxL is a paired-like homeobox gene involved in vertebrate eye morphogenesis. We examined RaxL protein expression patterns during chick retinal development in combination with ganglion cell markers including the RA4 antigen, cBrn-3, Islet-1 and neuronal type III beta-tubulin. Double-immunostaining demonstrated that downregulation of RaxL protein correlates with upregulation of ganglion cell markers in the ganglion cell layer (GCL). To explore this correlation in vivo, we performed gain- and loss-of-function experiments by electroporating retroviral vectors encoding wild-type and dominant-negative-RaxL into the optic vesicles of stage 10 chick embryos. Infection with virus expressing RaxL led to a 35% decrease in Islet-1-positive ganglion cells at E5.0 and a complete loss of ganglion cells at E15, with no effect on displaced amacrine cells in the GCL. When dominant-negative RaxL was expressed, the total number of cells in the GCL increased by approximately 40% at E5.0 but was reduced to 40% at E15, due to ectopic apoptosis in the GCL from E9 to E15. These results suggest that RaxL gives an inhibitory effect on ganglion cell development and that the loss of RaxL expression is required for maintenance of ganglion cells.

Animals↗

Experience with photocoagulation in Behçet's disease.

Between 1973 and 1987 we examined both eyes of 300 patients with the uveoretinitis-type lesions characteristic of Behçet's disease. Of the 556 eyes whose fundus could be examined, 38 eyes (6.8%) in 33 patients (11%) had developed retinal capillary nonperfusion, branch retinal vein occlusion, or retinal or disc neovascularization. These eyes were treated by photocoagulation, primarily to forestall vitreous hemorrhage and the development of neovascular glaucoma, as well as to decrease the macular edema resulting from vein occlusion. The treatment, which was well tolerated, was successful in closing retinal capillary nonperfusion areas and eliminating retinal neovascularization. Disc neovascularization was resolved completely in some cases, and partially in others.

Behcet Syndrome↗

Distribution and developmental regulation of AMPA receptor subunit proteins in rat retina.

PURPOSE: To learn more about a possible functional role of alpha-amino-3-hydroxy-5-methyl-4-isoxasole-propionate (AMPA) receptors in retinal development, the spatial distribution and temporal regulation of all AMPA receptor subunit proteins was studied in rats. METHODS: Immunohistochemistry was performed on retinal sections between embryonic days (E)20 and E21 and the adult stage by using specific antibodies against AMPA subunits GluR1 to 4. RESULTS: All AMPA subunits were expressed in the ganglion cell layer from E21 on. In the inner plexiform layer (IPL), discernible bands of labeling appeared at distinct retinal ages for the different subunits. GluR1 immunoreactivity (IR) was concentrated in two broad bands by postnatal day (P)3, whereas three bands were visible beginning on P9. Two bands were located in a region of the IPL where off-cells terminate, and one band was found in the innermost part of the IPL where on-cells terminate. In contrast, two bands of GluR2/3- and GluR4-IR in the IPL were only discernible beginning on P14 and seemed to be located between the bands of GluR1-IR. GluR2/3 and GluR4 were observed both in horizontal cells and in the outer plexiform layer from early developmental stages on. GluR1 was not found in the outer retina, indicating that horizontal and bipolar cell processes in the rat express AMPA receptors composed of subunits GluR2 to 4. Double-labeling experiments with cell-specific markers revealed the expression of subunits GluR1 to 4 in cholinergic and AII amacrine cells. CONCLUSIONS: AMPA receptors are expressed before synapse formation, indicating a role not only in fast signal transmission but also in the establishment of inner retinal circuits. The differences in spatial and temporal subunit expression suggest that different retinal cell types selectively express distinct types of AMPA receptors during development of the rat retina.

Animals↗

Asymmetry of retinal lesions in experimental scrapie after intracerebral inoculation of hamsters.

Hamsters injected into the right cerebral hemisphere with the scrapie agent developed retinal lesions to a greater extent in the contralateral than in the ipsilateral eye. This asymmetry was evident during the incubation period as well as during the clinical encephalopathy. The results explain much of the variation in the degree of retinal disease seen earlier at specific times after inoculation. Moreover, they strengthen the hypothesis that scrapie spreads via neurons.

Animals↗

Integrins and the development of three-dimensional structure in the Drosophila compound eye.

A stereotyped, three-dimensional network of cell-cell contacts mediated by adherens junctions and cell-extracellular matrix contacts mediated by focal adhesions defines the architecture of the Drosophila ommatidium. Developmental reconstruction shows that this network is built in an incremental and generally conservative sequence; contacts established early in eye development typically persist into adulthood. Reconstructions show that photoreceptor apical surfaces are involuted into the retinal epithelium and are subsequently elaborated to form the photosensitive rhabdomeres. Rhabdomeres become aligned to the ommatidial optical axis via their anchorage to the retinal floor at the cone cell plate, a specialized nexus of cell-cell and cell-extracellular matrix contacts. Parallel reconstructions of retinal development in integrin mutants show that several eye phenotypes trace their origin to the structural failure of the cone cell plate.

Animals↗

Independent spatial waves of biochemical differentiation along the surface of chicken brain as revealed by the sequential expression of acetylcholinesterase.

AChE-positive cells suddenly amass in a superficial layer of the neuroepithelium; this layer finally covers, in a sheat-like manner, the entire surface of the embryonic chicken brain. This feature is functionally not understood; however, it appears shortly after the neurons become postmitotic, and the lateral extensions of this layer can easily be traced using histochemistry on serial brain sections. The layer can therefore be exploited to delineate spatially the waves of onset of biochemical tissue differentiation. We have studied whole brains between stages 11 and 30 and provide the first complete spatial schemes of brain differentiation based on computer-reconstructed, two- and three-dimensional maps. The brain does not differentiate in one smooth coherent wave, but instead five separate primary AChE-activation zones are detected: the first originating at stage 11 ("rhombencephalic wave"), the second at the same time ("midbrain wave"), the third at stage 15 ("tectal wave"). A fourth zone develops later, at stage 18, from the bottom part of the telencephalon to the top. Retinal development also starts at stage 18. In a given area, it appears that AChE-development shortly precedes that of the formation of major fiber tracts. AChE might therefore represent a prerequisite for fiber growth and pathfinding.

Acetylcholinesterase↗

Incidence of vitreoretinal pathologic conditions within 24 months after laser in situ keratomileusis.

OBJECTIVE: To report for the first time a case series of vitreoretinal pathologic conditions after laser in situ keratomileusis (LASIK) and to determine its incidence. DESIGN: Case series. PARTICIPANTS: Five refractive surgeons and 29,916 eyes that underwent surgical correction of ametropia (83.2% were myopic) ranging from -0.75 to -29.00 diopters (D; mean: -6.19 D) and from +1.00 to +6.00 D (mean: +3.23 D) participated in this retrospective study. MAIN OUTCOME MEASURES: Vitreoretinal complications after LASIK. RESULTS: The clinical findings of 20 eyes (17 patients) with LASIK-related vitreoretinal pathologic conditions are presented. Fourteen eyes experienced rhegmatogenous retinal detachments (RDs). Two eyes experienced corneoscleral perforations with the surgical microkeratome when a corneal flap was being performed (one experienced a vitreous hemorrhage and the other later experienced an RD). In four eyes, retinal tears without RDs were found. In one eye, a juxtafoveal choroidal neovascular membrane (CNVM) developed. Retinal tears were treated with argon laser retinopexy or cryotherapy. Corneoscleral perforations were sutured, and the RD was managed with vitrectomy. The remaining RDs were managed with vitrectomy, cryoretinopexy, scleral buckling, argon laser retinopexy, or pneumatic retinopexy techniques. The CNVM was surgically removed. The incidence of vitreoretinal pathologic conditions determined in our study was 0.06%. CONCLUSIONS: Serious complications after LASIK are infrequent. Vitreoretinal pathologic conditions, if managed promptly, will still result in good vision. It is very important to inform patients that LASIK only corrects the refractive aspect of myopia. Complications of the myopic eye will persist.

Adolescent↗

Cloning and characterization of WDR17, a novel WD repeat-containing gene on chromosome 4q34.

As part of our project to generate a catalogue of genes with potential relevance to human retinal disease, we have cloned a transcript abundantly expressed in the human retina and testis. Analysis of the deduced 1322 amino acid protein sequence demonstrates that it encodes a novel WD repeat protein, termed WDR17. The N-terminal moiety of the WDR17 protein is predicted to consist of at least 12 conserved WD repeats that likely adopts a beta-propeller-like structure. Homology searches with the C-terminal region revealed no similarity to known or hypothetical proteins. However, putative orthologous ESTs with 82-91% identity to the human cDNA were found in several mammalian species including rodents, pig and cattle, suggesting that WDR17 represents an evolutionarily novel subtype of WD repeat proteins with unique function(s) in higher eukaryotes. Temporal expression analysis in the murine eye showed that transcription of WDR17 begins prenatally, suggesting a functional role of the protein in the early stages of retinal development. Human WDR17 maps to the same chromosomal interval as the locus for autosomal recessive retinitis pigmentosa (RP29) on 4q34, making it a candidate for this disease gene. Sequencing of the entire coding region of WDR17 in an affected patient of the original RP29 pedigree has not revealed any disease-causing sequence variations likely excluding WDR17 as the gene underlying RP29.

Amino Acid Sequence↗

Demonstration of cytomegalovirus retinitis by in situ DNA hybridization.

Five cases of the acquired immune deficiency syndrome (AIDS), each exhibiting retinitis, were studied by DNA hybridization technique to detect viral infection. Five involved eyes were obtained at the time of autopsy from three patients who had received no treatment for the retinitis. Retinal biopsy specimens were obtained at the time of surgery from two other patients who developed retinal detachments after being treated with ganciclovir (dihydroxy propoxymethyl guanine). DNA hybridization revealed cytomegalovirus in retina and retinal pigment epithelium in all five specimens from patients who had not been treated with ganciclovir. No hybridization occurred in the two retinal biopsy specimens obtained from the ganciclovir-treated patients. These results suggest that in situ DNA hybridization is a highly specific and easily interpretable means of establishing the tissue diagnosis of viral retinitis.

Cytomegalovirus↗

Spatial and temporal expression patterns of GDNF family receptor alpha4 in the developing chicken retina.

GDNF family receptor alpha (GFRalpha) receptors are involved in the regulation of different aspects of embryonic development such as proliferation, migration, differentiation and survival. To determine the possible role of GFRalpha4 in retinal development, we analysed its expression in the developing chicken retina. We found that GFRalpha4 is temporally co-expressed with c-ret. Both, the temporal and spatial expression of GFRalpha4 is developmentally regulated during retinogenesis and is first detected in cells of the ganglion cell layer at E6. As development of the retina proceeds, the expression of GFRalpha4 extends to cells of the inner half of the inner nuclear layer and to cells of the outermost cell row of the inner nuclear layer. Later on, GFRalpha4 expression is also found in additional cells of the outer half of the inner nuclear layer and in a subpopulation of photoreceptors. A central-to-peripheral gradient of retinal differentiation is evident, as the onset of GFRalpha4 expression is first detectable in the central retina, while it is delayed by two days in its periphery.

Animals↗

A decay of gap junctions in association with cell differentiation of neural retina in chick embryonic development.

Ultrastructural studies of thin-sectioned and freeze-cleaved materials were performed on developing retinal tissues of 3- to 9-day-old chick embryos to clarify the junctional structures between neural retinal cells and between neural retinal cells and cells of the pigmented epithelium. Frequency, size and position of gap junctions in developing neural retina are different at each stage of development. In 3-day-old embryos, some cells adhere to each other by gap junctions immediately below the outer limiting membrane of neural retinae. The size and number of gap junctions increase remarkably during 5-6 days of incubation. In this period of development, well developed gap junctions consisting of subcompartments of intramembrane particles are found between cell surfaces at both the outer limiting membrane region and the deeper portion of the neural retina. Gap junctions disappear thereafter, and at 7-5 days of incubation, small gap junctions are predominant between cell surfaces at the outer limiting membrane region, while the frequency of gap junctions in the deeper portion is very low. At 9 days of incubation, gap junctions are rarely found. Typical gap junctions are always found between neural retinal cells and those of the pigmented epithelium in embryos up to 7-5 days of incubation. Tight junctions are not found in the neural retina or between neural retina and pigmented epithelium throughout the stages examined.

Animals↗

Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation.

Galactose-fed dogs develop retinal capillary changes similar to diabetic retinopathy with pericyte degeneration as the initial lesion. This is followed by the formation of microaneurysms, hemorrhages, and some areas of acellularity. To investigate the mechanisms for selective pericyte degeneration, retinal capillary pericytes and endothelial cells isolated from beagle dog retina were cultured for 2 weeks in Dulbecco's modified Eagle's medium (DMEM) containing 50 mM D-galactose. Apoptosis was detected in pericytes but not endothelial cells by in situ terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end labelling (TUNEL) staining and the DNA fragmentation assay on agarose gel electrophoresis. This apoptosis was prevented by the addition of the aldose reductase inhibitor AL 1576 to the culture medium containing galactose. Apoptosis was not observed when pericytes were similarly cultured in control DMEM medium. These data support the premise that the selective degeneration of retinal capillary pericytes observed in galactose-fed dogs is linked to increased aldose reductase activity in these cells.

Aldehyde Reductase↗

Reversible retinal toxicity associated with retained intravitreal copper foreign body in the absence of intraocular inflammation.

PURPOSE: To report on a patient who developed retinal toxicity from an intraocular copper foreign body in the absence of any signs of chalcosis or inflammation. METHOD: Case report. RESULT: Removal of the copper foreign body resulted in electroretinographic improvement and the patient has retained good vision. CONCLUSION: Retinal toxicity from intraocular copper can be subclinical and such foreign bodies should be removed. Removal of the foreign body can be associated with at least partial reversal of retinal toxicity.

Adolescent↗

Ocular morbidity associated with intravitreal triamcinolone acetonide.

AIM: To report on the complications associated with the use of intravitreal triamcinolone acetonide (IVTA) in a tertiary referral hospital setting. MATERIALS AND METHODS: A retrospective case series review of all IVTA injections carried out over a period of 30 months. RESULTS: One hundred and thirty IVTA injections were performed; nine with limited local follow-up were excluded. Thus, 121 injections (108 patients, 114 eyes) were included in the study. Triamcinolone (4 mg) was used in all cases. Indications were diabetic macular oedema (n=41 eyes), retinal vein occlusions (n=27), postoperative cystoid macular oedema (n=24), exudative age-related macular degeneration (n=16), and others (n=6). No intraoperative complications were recorded. Postoperative intraocular pressure (IOP) readings of 22, 28, 35, and 40 mmHg or higher were recorded in 46.5, 29.8, 12.3, and 7.9% of eyes, respectively. IOP elevation was treated with antiglaucoma medication in all but one eye (0.9%) that required trabeculectomy and one (0.9%) that required vitrectomy with cataract extraction for suspected phacoanaphylactic glaucoma. Two eyes (1.8%) developed retinal detachment; both had previously been treated for retinal breaks. One eye (0.9%) developed culture-positive endophthalmitis. CONCLUSIONS: Significant morbidity is associated with IVTA injection; clinicians should be aware when considering treatment options.

Adult↗