Endophthalmitis after Lasiodiplodia theobromae corneal abscess

Background:Lasiodiplodia theobromae is an exceptional cause of human keratomycosis. Patient: We treated a 53-year-old man with fungal keratitis, which had been treated with topical betamethasone and gentamicin for 1 month, and endophthalmitis due toLasiodiplodia theobromae. Despite intensive systemic, topical and intravitreal fungicidal treatment, enucleation had to be performed. Results: The vitreous aspirate cultures were negative as of the second amphotericin intravitreal injection. However, histology revealed that the fungus was present in the cornea, ciliary body, iris and retina. Conclusion: The use of topical steroids may worsen the outcome of the infection.     

Interpretation of high-pass resolution perimetry with a probability plot

Background: The interpretation of high-pass resolution perimetry (HRP) fields can be difficult. An age-related probability plot was derived from a known data base to determine whether this improved specificity and sensitivity in early glaucoma detection Methods: Forty glaucoma patients with minor field loss and 40 normals of equivalent age and sex underwent HRP. All had previous Humphrey field data available for comparison. The detection of previously confirmed field defects by HRP was examined using different parameters. Results: Using the age-corrected 95% confidence levels gave the best results, with sensitivity of 82.5% (33/40) and specificity of 85% (34/40). Using the contour plot yielded lower sensitivity (67.5%), while subjectively eyeballing the ring printout gave higher sensitivity (90%), but led to poor specificity (72.5%). Conclusion: The use of a probability plot enhances the performance of HRP. A certain proportion of cases may be missed using one criterion alone, but combining the information with other indices can increase the yield.The authors have no proprietary interest in the equipment and technique described herein     

HLA antigens in a Japanese family with Behçet's disease

Background: Familial Behçet's disease is rare. Methods: HLA antigens in a Japanese family with Behçet's disease were examined. Results: The affected patients had HLA B51, and unaffected family members also had the same antigen. Conclusion: It is likely that not only HLA B51 but also other factors may be involved in the pathogenesis of Behçet's disease in Japanese patients.     

Early experience with intravenous immunoglobulin treatment in Wegener's granulomatosis with ocular involvement

Background: Pooled intravenous gammaglobulin (IVIg) was reported to be effective in the treatment of Wegener's granulomatosis (WG). No reports have been made on the effects of this new treatment on ocular manifestations of WG. Method: IVIg treatment was given to two patients suffering from WG with ocular involvement after several other treatment regimes had failed. Results: Although the systemic disease was under control, the ocular symptoms of both patients worsened during and after IVIg treatment. In one case an adverse effect consisting of retinal vasculitis was noted on two occasions. Conclusion: Although beneficial effects of IVIg treatment on WG have been previously described, the two cases with ocular involvement presented here did not reveal any positive response. Paradoxical and unpredictable reactions cannot be ruled out. Thus, patients treated with IVIg should be closely surveyed by an ophthalmologist.     

Unusual retinal pigment epitheliopathy and choroidopathy in carcinomatosis: A rare case of cancer-associated retinopathy

Background: Cancer-associated retinopathy is a syndrome causing ocular symptoms. It is a rare entity and only a few cases have been reported. Methods: A 67-year-old woman with small-cell endometrial carcinoma suffering from deterioration of visual acuity is presented. Results: The patient presented with extensive mottled changes of the retinal pigment epithelium, accompanied by diffuse subretinal fluid in the posterior pole and exudative retinal detachments inferior in both eyes. Conclusion: This patient suffered from a rare variety of cancer-associated retinopathy.     

Ocular findings in cystic fibrosis patients receiving vitamin A supplementation

Background: Vitamin A deficiency with eye symptoms has been reported in patients with cystic fibrosis who received the recommended daily intake of vitamin A. Methods: We measured serum retinol, dark adaptation, contrast sensitivity, and dry eye status in 35 adult cystic fibrosis patients to ascertain whether they had ocular signs or symptons. Results: Median serum retinol concentration was 1.95 mol/l, range 1.08–4.01 mol/l, with no values indicating vitamin A deficiency. Retinal light sensitivity was normal. Nineteen patients had reduced contrast sensitivity. Conjunctival imprints all showed plenty of goblet cells, but were characteristic of dry eye in 42% of patients (n=14). Decreased tear film stability was found in 49% (n=17), tear production was low in 31% (n=11), and 23% (n=8) showed an increased amount of dying epithelial cells. Nine patients (26%) had keratocon-junctivitis sicca according to the Copenhagen criteria. Conclusion: Our patients had no biochemical or clinical signs of vitamin A deficiency. We speculate that the high incidence of dry eye could be a primary manifestation of cystic fibrosis.     

Transforming growth factor-β regulates human retinal pigment epithelial cell phagocytosis by influencing a protein kinase C-dependent pathway

Background: Transforming growth factor- (TGF-) plays an important role in the pathogenesis of many ocular diseases, including proliferative vitreoretinopathy. We examined the effect of TGF- on the phagocytosis of rod outer segments by retinal pigment epithelium (RPE), which is a major function of RPE, and investigated the dependence of this effect on the protein kinase C (PKC) pathway. Methods: Phagocytotic uptake of fluoresceinated bovine rod outer segments was determined by flow cytometry. RPE cells were treated with TGF-1 or TGF-2 and their effects on phagocytosis were examined. The effects of various PKC inhibitors (calphostin C, staurosporine, and extended exposure to phorbol 12-myristate 13-acetate, PMA) and a stimulator (brief exposure to PMA) on RPE phagocytosis was evaluated. Results: Both TGF-1 and TGF-2 up-regulated RPE phagocytosis and PMA abolished the upregulating effect of TGF-. In contrast, PKC inhibition by staurosporine and calphostin C resulted in increased phagocytosis. A combination of TGF- and PKC inhibitor treatment did not produced any additive effect on phagocytosis. Conclusion: We concluded that TGF- up-regulates human RPE phagocytosis, but that this effect is counteracted by PKC activation. It is possible that this TGF--induced effect is due, in part, to a negative modulation of the PKC-dependent pathway.     

Role of protein tyrosine phosphorylation in rat corneal neovascularization

Background: Recent studies have suggested that tyrosine kinase pathways that are activated by angiogenic growth factors may play a role in corneal neovascularization. Methods: Corneal neovascularization was induced in rat corneas by chemical cauterization. At 6, 24, 48, 96, and 168 h after chemical cauterization the rat corneas without the corneal epithelium were prepared for gel electrophoresis. Total protein profiles of the corneal samples were examined by staining gels with Coomassie brilliant blue. Tyrosine-phosphorylated proteins, three angiogenic growth factors (basic fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor-B chain), and three intracellular signal proteins in the tyrosine kinase pathways (phospholipase C, SHC, and mitogen-activated protein kinase) in the corneal samples were examined by western blot analysis. A topical treatment of genistein eye drop (5 mg/ml) was used for inhibition of corneal neovascularization after chemical cauterization in rats. Results: In total protein profiles, three bands in the corneal samples were increased after cauterization. Overall tyrosine-phosphorylated proteins and all three angiogenic growth factors increased with progression of corneal neovascularization. The tyrosine-phosphorylated forms of three intracellular signal proteins were also increased after cauterization. Treatment with topical genistein was effective in inhibiting corneal neovascularization in rats. Conclusion: Protein tyrosine phosphorylation was involved in inflammation-induced corneal neovascularization. Tyrosine kinase inhibitors may have utility as inhibitors of corneal neovascularization.     

The in vitro effect of platelet-derived growth factor isoforms on the proliferation of bovine corneal stromal fibroblasts depends on cell density

Purpose: Recently, it has been shown that corneal stromal fibroblasts express the mRNA for PDGF--type receptors, while corneal epithelial cells express the mRNA for the PDGF B-chain, suggesting a role of PDGF isoforms in the regulation of corneal homeostasis and wound healing via an unidirectional epithelial to stromal paracrine interaction. The purpose of this study was to characterize the proliferative response of cultured bovine corneal stromal fibroblasts to PDGF isoforms. Methods: Bovine corneal stromal fibroblasts were seeded at a cell density of 60 cells/mm² (low density) and 120 cells/mm² (high density) and were cultured under serum-free conditions. Except for corresponding controls, PDGF AA, BB and AB (obtained by separate expression of cloned genes inE. coli) were added in concentrations ranging from 3.125 to 100 ng/ml. Cell numbers were determined after an incubation period of 6 days using a cell counter. Results: Stromal fibroblasts, when cultured at a high density, revealed constant cell numbers during the whole incubation period. Under these culture conditions, stimulation with PDGF AA, BB and AB led to a significant dose-dependent increase in cell proliferation. When cultured at a low cell density, stromal fibroblasts revealed a significant reduction of cell numbers after 6 days of incubation. This reduction was prevented by PDGF AA and AB isoforms in a dose-dependent manner. In contrast, PDGF BB was not effective. Conclusion: The results of the high-density assays suggest that PDGF isoforms act as mitogens for stromal fibroblasts during wound healing, when density of fibroblasts is high. The results of the low-density assays support the idea that PDGF AA and AB can prevent cell loss during corneal homeostasis when density of keratocytes is low.     

Cell types of secondary cataract: an immunohistochemical analysis with antibodies to cytoskeletal elements and macrophages

Background: The study was carried out to identify cell types of secondary cataract after extracapsular cataract extraction and implantation of an intraocular lens. Methods: Twenty-five formalin-fixed, paraffin-embedded pseudophakic human eyes with secondary cataract, obtained at autopsy, were studied and compared to a specimen from an anterior subcapsular cataract with a panel of six monoclonal antibodies (MAbs, to vimentin, cytokeratin (CK) 8 and 18, desmin, -smooth muscle actin, and the CD68 epitope of macrophages by the avidin-biotinylated peroxidase complex (ABC) method. Results: MAb Vim 3B4 to vimentin immunolabeled spindle-shaped cells in 16 of 17 central plaques of secondary cataract as well as cells in all 16 Soemmering's ring cataracts. Spindle-shaped cells reacted with MAb CAM 5.2 to CK 8 in 13 of 18 eyes, but only one specimen was labeled with MAb CY-90 to CK 18. No immunoreaction was seen with MAb D33 to desmin, whereas MAb 1A4 to -smooth muscle actin immunolabeled spindle-shaped cells in 15 of 18 plaques of secondary cataract. Macrophages were seen with MAb PG-M1 in 13 of 19 secondary cataracts. In the anterior subcapsular cataract, spindle-shaped cells under a wrinkled but otherwise intact capsule reacted with MAb Vim 3B4 to vimentin, MAb CAM 5.2 to CK 8, and MAb 1A4 to -smooth muscle actin. Conclusion: Spindle-shaped cells in secondary and anterior subcapsular cataracts react with antibodies to vimentin, CK 8 and -smooth muscle actin, suggesting them to be metaplastic epithelial cells that derive from the lens epithelium. -Smooth muscle actin persists in them at least 10 years postoperatively, but CK 8 starts to disappear after 3 years. Macrophages are one possible modulator of this transdifferentiation.The authors have no financial interest in any product or process mentioned herein.     

Evolution of ocular clinical and electrophysiological findings in pediatric Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is ahereditary autosomal-recessive disorder,characterized by mental retardation, obesity,pigmentary retinopathy,polydactyly and, only in males, hypogenitalism.Even though genetic studies haverevealed five different forms of BBS correlatedto distinct loci on differentchromosomes, a diagnosis of BBS is stillprimarily based on clinical data. Thepresent study discusses the evolutionof clinical ophthalmological andelectrophysiological characteristics ofBBS patients in developmental age.The main results obtained on asample of 13 pediatric patients are thefollowing: progressive loss of visualacuity arised early in the first decade of life ophthalmoscopic signs of pigmentaryretinopathy were present only in 46%of the children studied striking anomalies in theelectroretinogram were also detectedin the cases without pigmentary retinopathy the electroretinographic results, whendetectable, suggested a greater involvement of thephotopic system as against the scotopic system.     

Preoperative vitreous hemorrhage associated with rhegmatogenous retinal detachment: a risk factor for postoperative proliferative vitreoretinopathy?

Background: We conducted a prospective clinical study to elucidate the role of preoperative vitreous hemorrhage in the development of postoperative proliferative vitreoretinopathy (PVR) in primary rhegmatogenous retinal detachment. Materials and methods: We prospectively evaluated 409 eyes of 390 patients affected by primary rhegmatogenous retinal detachment referred before any failed attempt to reattach the retina. Single and multiple logistic regression analysis were used to test 14 categories of variables. Results: Postoperative PVR occurred in 48 (11.7% of 409 eyes). Postoperative PVR developed in 41 (11.8%) of the 347 eyes with no preoperative vitreous hemorrhage, and 7 (11.3%) of the 62 eyes with preoperative vitreous hemorrhage (P=0.90). The results of multiple logistic regression analysis showed that only four variables were significant factors which had independently and jointly an effect on the risk of postoperative PVR: (1) 90° or greater circumferential extent of the retinal tears; (2) preoperative PVR grade B; (3) preoperative PVR grade C-D; and (4) the use of cyrotreatment as the method of retinopexy. Conclusion: With the surgical techniques currently used, mild preoperative vitreous hemorrhage is not an independent risk factor for postoperative PVR in primary rhegmatogenous retinal detachment. The role of moderate and severe vitreous hemorrhage remains to be fully evaluated in a larger series of eyes.     

Indocyanine green and fluorescein angiography of surgically excised macular choroidal neovascularizations: correlations with histopathologic and ultrastructural findings

Background: Informations are expected from the histopathological study of surgically excised choroidal neovascular membranes (CNMs), particularly in relation to the angiographic aspects of vascular architecture. Methods: Fluorescein and indocyanine green (ICG) angiograms were studied together with the histopathological features of 12 surgically excised subfoveal CNMs in eyes affected by age-related macular degeneration (ARMD). Results: Instead of the early and delayed diffuse hyperfluorescence secondary to CNMs observed on fluorescein angiography (seven were well defined, five scar evolved), ICG revealed (a) very early hypofluorescence of the membrane bulk over the fluorescence of the outer choroidal vascular bed and (b) late hyperfluorescence gradually increasing and partially defining the border of membranes. CNMs with well-defined hyperfluorescent aspects were characterized by fibrovascular bulk lined on one side by retinal pigment epithelium. Fibrosis reaction predominated over the vascular components in scar-evolved membranes. Conclusions: Fluorescein and ICG angiographic differences in the appearance of CNMs could depend on (a) the morphological structure and size of the CNM (b) its location within the chorioretinal layers and (c) different molecular characteristics of the dyes used.     

Iatrogenic choroidal neovascularisation following argon laser photocoagulation for choroidal malignant melanoma

Background: Choroidal neovascularisation is known to occur following photocoagulation for choroidal melanomas. Its occurrence rate, possible causes and clinical impact were studied. Methods: Post-treatment fluorescein angiograms were reviewed from 18 patients who had received argon laser photocoagulation as sole treatment of their small choroidal melanomas, to look for choroidal neovascularisation. Where it was found an assessment of its clinical impact was made. Results: choroidal neovascularisation was found in 50% of cases. Choroidoretinal neovascularisation, found in five patients, caused vitreous haemorrhage in one patient but was otherwise benign. Choroidovitreal neovascularisation was found in four patients. It occurred early and altered their clinical management. Three of these patients had a vitreous haemorrhage, one of whom also suffered a retinal detachment. The three diabetic patients in the series all developed aggressive choroidovitreal neovascularisation. Tumour size, tumours location and number of treatment sessions did not appear to affect the occurrence of choroidal reovascularisation, nor did other medical or ocular conditions except for diabetes. Conclusion: Choroidal neovascularisation occurs commonly after melanoma photocoagulation. Although sometimes benign, it can be aggressive, particularly in diabetic patients, in whom it might be better to consider different forms of tumour treatment.     

Inhibition of corneal allograft reaction by CTLA4-Ig

Background: Activation of T cells requires both the interaction of T-cell receptor with major histocompatibility complex on the antigen-presenting cell and costimulatory signals, for instance the B7 antigens expressed on antigen-presenting cells and the CD28 molecule expressed on T cells. A recombinant fusion protein, CTLA4-Ig, has been produced that contains the extracellular domain of human CTLA4 fused to IgGl constant region and that binds the B7 molecule with high affinity. Blocking the CD28/B7 interaction with CTLA4-Ig inhibits T cell activation in vitro and in vivo. Methods: We used CTLA4-Ig in a fully MHC-mismatched mouse keratoplasty model. The animals were divided into four groups: (1) no treatment, (2) intraperitoneal treatment with 130 g CTLA4-Ig, (3) intraperitoneal treatment with 300 g CTLA4-Ig, (4) subconjunctival treatment with 290 g CTLA4-Ig. Results: The allograft reaction occurred in untreated animals between days 12 and 16 (mean 13.5). While topical application of CTLA4-Ig seemed to shorten the graft survival (mean 11.6 days) and systemic application of 130 g had no influence (mean 14.0), only intraperitoneal injection of 300 g of CTLA4-Ig prolonged the survival of allografts (mean >20 days) (P<0.01). Conclusion: CTLA4-Ig prolonged significantly the survival of corneal allografts in a fully MHC-mismatched mouse keratoplasty model, but the small antigen load of the corneal transplant and the anterior chamber-associated immune deviation (ACAID) may have a disadvantage to induce tolerance in this model of CTLA4-Ig therapy.Presented at JERMOV 1996 in Montpellier     

DNA-based HLA class II postmortem typing: evaluation of different techniques for prospective corneal allografting

Background: The objective of this study was to establish DNA-based HLA-DR postmortem tissue typing techniques in order to improve the quality and quanity of fully HLA-typed corneas for prospective allografting. Methods: Four hundred and thirty-seven cornea donors were investigated. DNA was derived from cultivated retinal pigment epithelial cells by spin column purification or a salting out technique, and from scleral tissue by a very simple boiling method. Donors were typed by hybridization of polymerase chain reaction (PCR) products with sequence-specific oligodesoxynucleotide probes (PCR-SSOP) or by PCR with sequence-specific primers (PCR-SSP). Twenty-two of the donors were pretyped by serology. Results: We observed high concordance (96%) between the results of DNA-based postmortem typing and the serological lymphocytotoxicity test. Furthermore, the distribution of the HLA-DR specificities that were detected correlated well with the distribution in a control population. Conclusions: The results of this study demonstrate that both PCR-SSP and PCR-SSOP allow prospective allocation of HLA class II-matched corneas with high accuracy.     

Relaxing incisions with compression sutures for control of astigmatism after penetrating keratoplasty

Background: Ten percent of patients with persisting postoperative astigmatism following penetrating keratoplasty (PK) require surgical re-intervention, despite an otherwise successful transplant. Relaxing incisions (RIs) in combination with compression sutures seem to be the preferable procedure. However, poor predictability and lack of long-term experience complicate the issue. Here we report the 2-year follow-up results of 25 patients with high PK astigmatism treated by means of RIs and compression sutures Methods: Commonly, free-handed RIs were placed at the graft-host interface and 10–0 nylon compression sutures were placed perpendicular to the incisions. PK sutures had been removed no less than 4 months prior to refractive surgery Results: Nineteen eyes regained a functional vision of >- 0.4. The net decrease in astigmatism was 6.1 ± 4.3 D (47 ± 21 %). The mean vector-corrected change in astigmatism was 13.1 ± 5.7 D. Cylinder axis variation was reasonably low, with a correlation of attempted versus achieved axis of r=0.85. Within the first 3 months after operation the induced astigmatism regressed by, on average, 5.5 ± 4.3 D, making intraoperative overcorrection necessary. As an inevitable side effect, refractive procedures resulted in a myopic shift (4.7 ± 6.9 D) in spherical equivalence Conclusion: RIs and compression sutures are very useful in reducing postkeratoplasty astigmatism if correction of extremely high cylinder (> 10 D) is not intended. However, predictability still remains unsatisfactory and more than one operation may be required.     

A comparison of blood pressure changes in phacoemulsification cataract surgery with topical and retrobulbar block local anesthesia

Background: Changes are observed in blood pressure (BP) levels during cataract surgery, although BPs are considered to remain stable under local anesthesia. We evaluated the daily, pre- and postoperative BPs of 2270 patients after cataract surgery performed under either topical anesthesia or retrobulbar block. Methods: All operations were performed by the same surgeon using the same method of phacoemulsification and aspiration with posterior chamber intraocular lens implantation under local anesthesia. Results: The mean daily BP was 99.3±14.2 mm Hg; the mean preoperative BPs increased and then the postoperative BPs decreased. The postoperative BPs of the retrobulbar injection group decreased significantly more than those of the topical application group. In 833 cases, the systolic BP changed by more than 20 mm Hg. Even when the patients were hypertensive, the preoperative and postoperative BPs decreased in the same manner. Conclusion: The present study shows that, following surgery with retrobulbar block anesthesia, BP decreases to a greater extent than with topical anesthesia. Physicians should be aware of the high proportion of cases in which the systolic BP changes by more than 20 mm Hg.     

Diclofenac sodium and cyclosporin A inhibit human lens epithelial cell proliferation in culture

Purpose: To investigate the effect of diclofenac sodium salt and cyclosporin A (CsA) on human lens epithelial cell (HLEC) growth in culture. Methods: Cultures of HLEC were obtained from anterior capsules from extracapsular cataract surgery. Third-passage cells were seeded in 96-well plates in 0.1 ml culture medium. Cytotoxicity was estimated by the tetrazolium test in confluent monolayers after 24 h exposure to a wide range of concentrations of diclofenac and CsA. The effect of subcytotoxic concentrations of diclofenac and CsA on HLEC proliferation in subconfluent cultures was evaluated after 24 and 72 h of exposure. To investigate the relationship between PGEZ synthesis and the inhibitory effect of these drugs, after 24 h of exposure to diclofenac and CsA the production of PGE₂ was measured by radioimmunoassay. We also tested the effect of exogenous PGE₂ addition to diclofenac 72-h-treated cultures. Results: Diclofenac and CsA (at concentrations 65 M and 2.5 M, respectively) inhibited the proliferation of subconfluent cultures of HLEC in a dose-dependent fashion. Diclofenac inhibits PGE₂ synthesis, while CsA at high doses stimulates PGE₂ synthesis of cultured HLEC. Exogenous PGE₂ addition reversed in part the inhibitory effect of diclofenac. Conclusions: Diclofenac and CsA at appropriate doses are effective in inhibiting cultured HLEC proliferation. This could be of interest to prevent posterior capsule opacification. Further in vivo experimental studies seem worthwhile.None of the authors have financial or proprietary interests in any of the products mentioned in this article     

Isovolemic hemodilution increases retinal tissue oxygen tension

Background: Therapeutic isovolemic hemodilution has been reported to improve blood flow and oxygen delivery. Few reliable measurements have been made, however, showing the effect of hemodilution on tissue oxygen tension. Methods: We measured retinal oxygen tension during experimental isovolemic hemodilution in normal cats. Polarographic oxygen microelectrodes were placed in the vitreous humor within 100–200 m of the retinal surface.Results: Tissue oxygen tension increased initially during isovolemic hemodilution to a maximum approximately 50% above baseline at approximately two thirds of the original hematocrit level. Hemodilution beyond this point to lower hematocrits caused a steady decline in tissue oxygen tension. Cardiac output measured in one cat undergoing isovolemic hemodilution increased as hematocrit was lowered, but the cardiac erythrocyte flux actually decreased steadily.Conclusion: The observed increase in tissue oxygen tension with hemodilution appears to be explained by a lesser reduction in capillary than in systemic hematocrit, coupled with an increased capillary blood flow. The increase in tissue oxygen tension we observed could in part explain the clinically beneficial effects of hemodilution.