[Decompression retinopathy after intraocular surgery]. / Retinopatía por descompresión después de cirugía intraocular.

OBJECTIVE: To report 10 instances of decompression retinopathy (DCR) developing after intraocular surgery. METHODS: This was a case series of 9 patients (10 eyes). Decompression retinopathy occurred after trabeculectomy (4 eyes), phacomulsification (3 eyes), Ahmed valve placement (1 eye), silicone oil removal (1 eye) and vitrectomy (1 eye). Fundus evaluation and fluorescein angiography were performed in all instances. RESULTS: Superficial, subhyaloidal, and deep retinal hemorrhages were noted in the posterior pole and peripheral retina; some of these had a white center. Nine (90%) of 10 eyes had a previous diagnosis of glaucoma, 6 having primary open-angle glaucoma, 2 neovascular glaucoma and 1 secondary glaucoma associated with intravitreal silicone oil. The patient without glaucoma had a history of cataract surgery and a vitrectomy to close a macular hole. The mean preoperative intraocular pressure (IOP) was 36.6 mm Hg (range: 15 to 58 mm Hg) despite maximal medical therapy in those patients with glaucoma. Fluorescein angiography demonstrated hypofluorescence throughout the study associated with superficial, and deep retinal hemorrhages. On the first post-operative day, visual acuity (VA) decreased more than 2 ETDRS lines in all cases. A pars plana vitrectomy (PPV) was performed in 5 eyes. All patients improved more than 2 ETDRS lines at a mean of 9 months after DCR. CONCLUSIONS: A gradual decrease of IOP pre-operatively and intra-operatively is recommended in order to avoid this complication. Early vitrectomy represents a useful treatment in many cases. A previous history of glaucoma seems to be an important risk factor for the development of DCR.

Rapid induction and clearance of TGF beta 1 is an early response to wounding in the mouse embryo.

The TGF beta family of growth factors has been implicated as playing a significant role in many aspects of embryonic morphogenesis, and also as a mediator of adult tissue repair processes. Unlike the situation in the adult, tissue repair in the embryo does not result in scarring, and it has been suggested that this might be due, in part, to reduced levels of growth factors, particularly TGF beta, at the wound site. We have examined the expression patterns of TGF beta genes following wounding of limb bud lesions in cultured E11.5 mouse embryos. The timetable of wound closure was investigated by standard light and electron microscopy from the time of wounding until the lesion had re-epithelialised 24 hours later. The expression of transcripts for each of the three TGF beta genes was examined at various time points during the healing process using radioactive in situ hybridisation to tissue sections and wholemount non-radioactive in situ hybridisation to embryo pieces. Within 1 to 3 hours of wounding, transcripts encoding TGF beta 1 were rapidly induced within the epithelial cells of the wound margin, particularly those cells at the ventral aspect of the wound. By 3 to 6 hours post-wounding, TGF beta 1 transcripts were detectable in the mesenchyme of the wound bed. No TGF beta 3 induction was observed, and possible TGF beta 2 induction was largely obscured by endogenous expression associated with pre-cartilage mesenchymal condensation. Immunocytochemical analysis of tissue sections of the wound demonstrated a rapid induction of TGF beta 1 protein within 1 hour post-wounding, but also a subsequent rapid clearance of the protein from the wound site such that, by 18 hours post-wounding, TGF beta 1 levels had returned to near background. These data are discussed in terms of the molecular mechanisms underlying embryonic wound healing and the significance of the results to an understanding of scarring following adult tissue repair.

The role of TGF-beta s in mammalian development and neoplasia.

To date, three mammalian TGF-beta isoforms have been identified, each encoded by different genetic loci. Through each is very similar in primary amino acid structure, there are clear differences both in the mature bioactive peptide region and in the latency-associated peptide, which could potentially confer differential biological specificity. As one route to investigate differential biological function in vivo we have used gene specific probes for in situ hybridization studies to examine the distribution of RNA transcripts during mammalian embryogenesis. Mouse embryos from 6 to 14.5 gestational age and human embryos from 32 to 57 days post-fertilization have been probed. A general conclusion from these studies is that each TGF-beta gene has a distinct, through overlapping, pattern of transcript distribution and that this pattern, in most cases, is conserved between mouse and man. We have focused on the biological function the TGF-betas play in certain epithelia and in cardiogenesis, which will be discussed in this presentation.

Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo.

We have compared the expression of the genes encoding transforming growth factors beta 1, beta 2 and beta 3 during mouse embryogenesis from 9.5 to 16.5 days p.c. using in situ hybridisation to cellular RNAs. Each gene has a different expression pattern, which gives some indication of possible biological function in vivo. All three genes appear to be involved in chondroossification, though each is expressed in a different cell type. Transcripts of each gene are also present in embryonic epithelia. Epithelial expression of TGF beta 1, beta 2 and beta 3 RNA is associated with regions of active morphogenesis involving epithelial-mesenchymal interactions. In addition, widespread epithelial expression of TGF beta 2 RNA can be correlated with epithelial differentiation per se. The localisation of TGF beta 2 RNA in neuronal tissue might also be correlated with differentiation. Finally both TGF beta 1 and beta 2 transcripts are seen in regions actively undergoing cardiac septation and valve formation, suggesting some interaction of these growth factors in this developmental process.

Transforming growth factor betas in mammalian embryogenesis.

Type beta transforming growth factors (TGF beta s) are members of a large superfamily of related proteins, each of which plays a pivotal role in embryonic processes. The TGF beta s per se are at least five in number, though only three isoforms have been identified in mammals. Here we will review the evidence, taken from in vitro studies on bioactivity and histochemical localization of RNAs and encoded proteins in vivo, that TGF beta 1, beta 2 and beta 3 are involved in several mammalian developmental processes, including control of growth, differentiation, tissue inductions and morphogenesis.

Predictive testing for Huntington's disease with linked DNA markers.

Availability of new DNA markers, more tightly linked to the Huntington's disease (HD) locus than the original G8 (D4S10) probes, has improved predictive accuracy for both presymptomatic and prenatal exclusion testing. 50 predictive tests were carried out on high-risk individuals. 6 of these were on first-trimester chorionic villus biopsy specimens; in 2 cases the HD gene was not transmitted to the fetus while in 4 cases no exclusion could be made. The remaining 44 tests were on adults with either 25 or 50% risk of manifesting the disease; 19 had a greatly increased risk and 25 a substantially decreased risk of HD. Family structures in Scotland are suitable for testing about 75% of potentially affected individuals, and the new generation of DNA markers makes virtually all families fully informative.

Genetic linkage between Huntington's disease and D4S10 (G8) in Scottish families.

Genetic linkage between Huntington's disease (HD) and polymorphic DNA markers at the D4S10 locus has been investigated in 16 Scottish families. A maximum lod score of 3.499 at a recombination fraction of 0.07 was found, with 95% confidence limits of 0.02 and 0.22. Only one obvious recombinant was detected, and the wide confidence limits probably reflect the large number of unaffected individuals whose risk could only be estimated empirically.

Prenatal exclusion testing for Huntington disease using the polymerase chain reaction.

Prenatal exclusion of Huntington disease (HD) may be carried out by analysis of cosegregating DNA markers on a first-trimester chorionic villus sample. The conventional Southern blot method is time-consuming and requires microgram quantities of DNA and milligram quantities of villus tissue. The use of the polymerase chain reaction (PCR) to amplify genomic DNA by a factor of 10(7) or more makes it possible to do analyses on very small samples in a few hours and without recourse to Southern blotting or hybridization with radioactive probes. We report on a fetus at risk of HD; prenatal testing was carried out by using the PCR to amplify a polymorphic DNA sequence adjacent to the HD locus. The risk of the fetus inheriting the HD gene could not be excluded and the pregnancy was terminated. This represents an example of gene tracking by using amplification of a restriction fragment length polymorphism at some distance from the relevant mutation.

Prenatal exclusion testing for Huntington's disease: a problem of too much information.

At eight weeks of pregnancy a couple were informed that the prospective father's mother had died of Huntington's disease (HD). There were no living affected members in the immediate family to confirm the diagnosis. By inspection of the local genetic register, it was established that it was indeed HD segregating in the extended family. Genotyping of the prospective mother and father, the father's unaffected father, and his unaffected maternal grandmother was carried out using a battery of polymorphic DNA markers, including a new probe which has a very low recombination rate with the HD locus. Analysis of DNA from a chorionic villus sample taken at 10 weeks of pregnancy showed that the fetus must have inherited a chromosome from its father's affected mother. Its risk of developing HD was 47%. If the genotype of the unaffected maternal grandmother was taken into account, the risk was reduced to 42%. Neither risk was considered acceptable by the prospective parents and the pregnancy was terminated at 12 weeks' gestation. Prospects for future pregnancies are good, with a 50% chance of having a child whose risk of inheriting the HD gene is less than 1.5%. In retrospect it was noted that although genotyping of the maternal grandmother had refined the fetal risk, it had also nearly contributed to an inadvertent and unwanted predictive test for HD on the father. This case makes the point that in prenatal exclusion testing, linkage information must be generated with considerable care.