[Carotid-cavernous fistulas: Clinical features, management and differential diagnosis]. / Fistules carotidocaverneuses : présentation clinique, prise en charge et diagnostics différentiels.

Carotid-cavernous fistulas are abnormal communications between the carotid system and the cavernous sinus. Depending on their direct or indirect nature, they have different clinical manifestations and management. Are discussed in this paper: first the anatomy of the cavernous sinus, then clinical signs, diagnosis, management and differential diagnosis of carotid-cavernous fistulas.

[Treatment of postoperative cystoid macular edema (Irvine-Gass syndrome) with dexamethasone 0.7 mg intravitreal implant]. / Traitement de l'œdème maculaire postopératoire (syndrome d'Irvine-Gass) par implant intravitréen de dexaméthasone 700µg.

PURPOSE: To evaluate the efficacy of dexamethasone 0.7 mg intravitreal implant in patients with postoperative cystoid macular edema. MATERIALS AND METHODS: Fourteen patients' charts with postoperative cystoid macular edema were retrospectively reviewed. The main outcome measures were best-corrected visual acuity (BCVA) and mean central retinal thickness (CRT). RESULTS: Patients' mean age was 72.1 years old. Five patients were diabetic. All patients had previously been treated with non-steroidal anti-inflammatory drops. Four patients had received a previous treatment with intravitreal ranibizumab. The mean follow-up period was 8.7 months. Mean BCVA before intravitreal dexamethasone was 0.72 logMAR. After injection, it improved to 0.50 at month 1, was 0.47 at month 3, and 0.60 logMAR at month 12. The pre-injection mean CRT was 598 µm. It improved to 286 µm at month 1, 338 µm at month 3, and was 441 µm at month 12. Eight patients received 2 intravitreal injections of dexamethasone. Five patients presented with elevated intraocular pressure during follow-up, which was treated with drops. CONCLUSIONS: Intravitreal dexamethasone injection improved visual acuity and macular thickness at month 1 and month 3 in patients with postoperative cystoid macular edema. A second injection was necessary after a mean period of 5 months.

[Arteriovenous malformation of the brain revealed through a visual blur and Adie's pupil]. / Tumeur vasculaire cérébrale révélée par un flou visuel concomitant à la découverte d'une pupille d'Adie.

INTRODUCTION: Arteriovenous malformations of the brain (BAVMs) are a relatively rare group involving intracranial vascular lesions (telangiectasia, cavernous malformation, venous anomaly). We report the case of a patient who presented an atypical visual symptomatology revealing a BAVM. OBSERVATION: A 48-year-old woman consulted for a recent bilateral visual blur. In darkness, discrete anisocoria appeared on the left eye. At the biomicroscopy light examination, we found areflexic semi-mydriasis (direct and consensual) on the left eye; the light reflex (direct and consensual) on the right eye was normal. During the accommodative reflex test the left pupil contracted. We propose the diagnosis of Adie's pupil, which was confirmed by the pilocarpine test (0.125%). We decided to examine the visual field because the symptomatology of the visual blur remained unexplained. The visual field showed a left homonymous inferior lateral scotoma. MRI showed a right occipital arteriovenous malformation. DISCUSSION: A quick examination could confuse painless anisocoria with a compression of the IIIrd intrinsic left nerve. This recent scotoma revealed BAVM progression. The natural history of BAVMs shows that the essential risk of these injuries is the onset of an intracranial hemorrhage. To reach a radical therapeutic decision, a cerebral arteriography clarifying the afferent and efferent vascularity of the nidus was carried out. CONCLUSION: This case is original in that it associates the concomitant discovery of a BAVM and Adie's pupil. Symptomatic BAVMs are extremely serious. Planning their treatment requires multidisciplinary cooperation in order to reduce the risk of mortality.

Results of proton therapy of uveal melanomas treated in Nice.

PURPOSE: To present the first results of uveal melanomas treated with the Medicyc Cyclotron 65 MeV proton beam facility in Nice, analyzing the factors that affect the cause-specific survival (CSS), metastatic rate, and reporting the visual outcome. METHODS AND MATERIALS: This study concerns 538 patients referred by French institutions between June 1991 and December 1996. The eye and tumor parameters were measured using ultrasonography and angiography. Since 1994, CT scans were performed in most patients to help determine the axial length and the shape of the ocular globe. Tantalum clips were inserted around the tumor by the referring ophthalmologist. There were 349 posterior pole tumors (64.9%), 130 equatorial tumors (24.1%), and 59 ciliary body tumors (11%). Two hundred four patients (37.9%) had T1 or T2 tumors, and 334 patients (62.1%) had T3 or T4 tumors. The median tumor diameter was 14.6 mm, and the median tumor height was 5.1 mm. All patients received 52 Gy (57.20 Gy Co-equivalent dose) on 4 consecutive days. The data were analyzed by December 1997. RESULTS: The CSS was 77.4% at 78 months, the overall survival was 73.8% and the local control was 89.0%. The CSS was not influenced by the patient age or the site of the tumor. It was 81.5% for T1 and T2 tumors, versus 75% for T3 and T4 tumors (P = 0.035). It was found that the tumor diameter, rather than the height, was the most important parameter affecting outcome. The metastatic rate was 8%. It depended on the T stage, tumor diameter and thickness, but not the tumor site. Thirty-eight enucleations were performed, most of them due to tumor progression and/or glaucoma. One-third of the patients in whom visual acuity was adequately scored before and after treatment had a stable, if not improved vision, and half the patients retained useful vision after treatment. CONCLUSION: The outcome of patients suffering from uveal melanoma and treated with high-energy protons compares favorably with other techniques of treatment. The tumor dimensions affected CSS and metastatic rate. Even though two-thirds of patients had posterior pole tumors, half of them retained useful vision.

Class II histocompatibility antigen expression by cellular components of vitreous and subretinal fluid in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is the major cause of failure in retinal detachment surgery. It is characterized by the formation of membranes extending along both surfaces of the detached retina and within the vitreous, but the nature of the growing cells has not yet been determined. Using cytologic and immunocytologic procedures with 13 different monoclonal antibodies directed against Class II histocompatibility antigens and various markers of epithelial and immunocompetent cells, 30 specimens were studied of vitreous or subretinal fluid removed from patients with PVR. Five main types of cells could be identified: heavily pigmented cells, poorly pigmented ones, large totally unpigmented macrophage-resembling ones, smaller unpigmented cells, and lymphocytes. Analysis of intravitreal pigment granules, using autofluorescence by epiillumination and cytologic procedures, showed two different populations of pigmented cells: one with autofluorescent lipofuscin granules and the other with exclusively melanin pigment. Immunostaining procedures confirmed the epithelial nonmacrophage lineage of the intravitreal and subretinal cells because most of these cells were positive for cytokeratin but negative for macrophage markers. In addition, 40-100% of these epithelial-derived cells strongly expressed Class II histocompatibility antigens HLA-DR and -DQ. Lymphocytes were found in 13 specimens; B-cells were seen, but no T-lymphocytes could be identified. These results confirm the involvement of retinal pigment epithelial cells and the strong morphologic changes they undergo during the course of PVR. Moreover, the expression of Class II histocompatibility antigens by the growing cells may be related to inflammatory phenomena, but their eventual role in the development and the extension of periretinal proliferation has not been determined.

Transferrin receptor expression by retinal pigment epithelial cells in proliferative vitreoretinopathy.

Immunotoxins directed against a membrane marker of cell proliferation, transferrin receptor, were investigated to inhibit the growth of retinal pigment epithelial (RPE) cells in proliferative vitreoretinopathy (PVR). We undertook an immunocytological study in specimens of vitreous, subretinal fluid, and epiretinal membranes from patients with PVR to address the expression of transferrin receptor by proliferating pigment epithelial cells during the course of PVR and in normal human ocular structures. Thirty four specimens of vitreous and subretinal fluid, as well as seven epiretinal membranes, were immunocytologically examined using monoclonal antibodies to transferrin receptor. They showed a strong expression of this marker by a large majority of the cells in these two periretinal fluids (mean percentages 80 and 91% in vitreous and subretinal fluid, respectively). In contrast, only a few cells within epiretinal membranes were found to express transferrin receptor. In normal human eye sections conjunctival and corneal epithelial cells, subcapsular epithelium of the lens strongly expressed transferrin receptor, whereas RPE cells remained negative to antitransferrin receptor antibodies. A few iris or ciliary pigment epithelial cells reacted weakly. Thus, this study shows that most intravitreal and subretinal fluid proliferating cells strongly express transferrin receptor on their surface. Also confirmed is that immunotoxins to this membrane antigen could constitute potentially useful therapeutic agents in PVR.

Asymmetric synthesis of functionalized 1,2,3,4-tetrahydroquinolines.

[reaction: see text] Highly enantioselective rhodium-catalyzed asymmetric hydrogenation (>98% ee) and Sharpless epoxidation (>90% ee) of o-nitrocinnamyl substrates lead to intermediates that can be transformed into tetrahydroquinoline derivatives. Starting materials are produced in high-yielding Heck reactions of an o-nitroaryl iodide and alpha-acetamidoacrylate or methyl acrylate.

Immunohistologic study of proliferative vitreoretinopathy.

An immunohistologic study was performed on pars plana specimens obtained by biopsy in ten patients with rhegmatogenous retinal detachment, with or without proliferative vitreoretinopathy. Using immunofluorescence or immunoperoxidase procedures, linear deposits of IgG, IgA, and complement components were found in the eight cases of retinal detachment with proliferative vitreoretinopathy at the basal pole of the pigment epithelial cells and within the stroma. In contrast, these deposits were absent from the normal pars plana and from the retinal detachment without proliferative vitreoretinopathy. Moreover, pigment and nonpigment epithelial cells were found to express HLA-DR and HLA-DQ determinants in six of the eight patients with proliferative vitreoretinopathy. Our results are similar to those obtained in a previous study on proliferative diabetic retinopathy, which suggests the involvement of autoimmune phenomena in proliferative diseases and eventual interactions between the immune system and peptide growth factors. However, whether or not this immune reaction functions in the initiation or extension of intraocular proliferative syndromes remains to be determined.

Immunohistopathologic findings in proliferative diabetic retinopathy.

We performed immunopathologic studies on pars plana specimens obtained by biopsy in patients with diabetes mellitus type I or II and by autopsy in diabetic patients and normal subjects. Frozen sections were treated with several antisera, including anti-IgG, complement components, and major histocompatibility complex antigens, as well as anti-factor VIII to detect vascular structures. The results showed IgG in a linear pattern at the basal pole of pigment epithelial cells and complement deposits of C3c, C3d, and C4 at the same location and in the stroma. HLA-DR expression was found at the level of the pigmented cells. These data suggest that some autoimmune processes may be involved in proliferative diabetic retinopathy at the level of the pigment epithelium, but it is unknown whether they are an epiphenomenon of neovascularization or if they play a role in its initiation.

Class II antigen expression in diabetic preretinal membranes.

Using immunofluorescence and immunoperoxidase procedures, we found large amounts of IgG, IgA, IgM, and IgE, as well as C1q, C3c, and C3d, in the connective stroma and within the vascular walls on eight specimens of preretinal membranes obtained from diabetic patients with proliferative retinopathy. The membranes contained many isolated human leukocyte antigen (HLA) DR- and DQ-expressing cells, and vascular endothelial cells strongly expressed class II determinants. Monoclonal antibodies to immunocompetent cells disclosed only rare B lymphocytes or suppressor/cytotoxic T cells and few monocytes. These findings confirm previous evidence of immune reactions in the pars plana of patients with proliferative diabetic retinopathy, and suggest that an autoimmune reaction is a factor in this complication. It is yet not possible to determine whether this reaction is a nonspecific consequence of the vasoproliferative processes or if it plays a direct role in the development and extension of preretinal membranes.

Immunohistologic study of epiretinal membranes in proliferative vitreoretinopathy.

We performed an immunohistologic study on 11 specimens of epiretinal membranes surgically obtained from patients who had rhegmatogenous retinal detachment with proliferative vitreoretinopathy. Immunostaining procedures were used to identify immunoglobulin and complement deposits, to visualize class II antigen expression by proliferating cells, and to determine eventual infiltration by cells of the immune system. Diffuse deposits of IgG, IgA, IgE, C1q, C3c, and C3d were found in epiretinal membranes, whereas numerous cells, including glial or pigmented epithelial cells, expressed HLA-DR and HLA-DQ antigens. Some macrophages and B or T8 lymphocytes were identified. These results suggest activation of the immune system during the course of proliferative vitreoretinopathy. Class II antigen expression could be dependent upon growth-promoting factors and interferon gamma and could play a crucial role in this immune reaction, which resulted in immunoglobulin deposition and activation of complement. However, the eventual role of immune phenomena in the extension of proliferative processes remains to be determined.

Detection of HBs antigen, DNA polymerase activity, and hepatitis B virus DNA in tears: relevance to hepatitis B transmission by tears.

Hepatitis B surface antigen, DNA polymerase, and hepatitis B virus DNA have been sought in the tears of 72 patients. These markers were detected in a high percentage of hepatitis B carriers, which proves the presence of hepatitis B virus in the tears and raises the question of its eventual transmission in this way. The severity and extreme contagiousness of hepatitis B together with the increasing number of virus carriers justify systematic sanitary rules among ophthalmic clinicians and staff, but vaccination remains the best mean of limiting the spread of the disease.

Immunopathological findings in conjunctival cells using immunofluorescence staining of impression cytology specimens.

The conventional technique of impression cytology provides a non-invasive method for the evaluation of conjunctival epithelium alterations. Using indirect immunofluorescence procedures two inflammatory markers, class II MHC antigens HLA DR and the receptor to IgE (CD23), were sought in impression cytology specimens obtained from 80 patients. In normal subjects conjunctival epithelial cells did not show any reactivity. Only scattered dendritic cells were found to express class II antigens but not the receptor to IgE. In contrast patients with chronic conjunctivitis of various aetiologies, mainly infectious or allergic, had 40-100% of brightly positive conjunctival cells for one or both antigens. In these cases epithelial cells and goblet cells reacted similarly. Twenty four eyes in 12 patients with idiopathic dry eye syndrome disclosed results similar to those from normal conjunctival specimens. However 18 other specimens from patients suffering from idiopathic tear deficiency but undergoing multiple substitutive treatments for dry eye had moderate to strong positivity for HLA DR and/or the receptor to IgE (20-100% of cells). As these results were independent of the degree of squamous metaplasia the expression of these membrane markers may reflect local inflammation in addition to tear deficiency, possibly due to sensitisation to the eye drops used. These immunocytological techniques thus provide useful methods of investigating conjunctival inflammation and allergy. They may constitute valuable aid in the diagnosis and appropriate treatment of ocular surface disorders.

Evaluation of antiproliferative effects of the somatostatin analogue somatuline in a rabbit model of traction retinal detachment.

As growth hormone (GH) and insulin-like growth factor type I (IGF-I) have been suggested to be involved in the development of some proliferative ocular disorders, we investigated the eventual antiproliferative properties of a long acting somatostatin analogue, somatuline or BIM23014 (IPSEN Biotech, France), in an original model of experimental proliferative vitreoretinopathy. Two studies were separately done to investigate respective effects of subcutaneously- and intravitreally administered somatuline. Injections of 10(7) human platelets freshly prepared from a unique normal donor were injected into the vitreous, cavity of pigmented rabbits. The first experiment consisted of evaluating vitreoretinal proliferation in 17 eyes from rabbits receiving subcutaneous injections of 25 micrograms/kg of BIM23014, given twice a day, from the day after injection for one month. A group of 14 eyes served as non treated controls. The second experiment was conducted in 33 eyes: 10 received intravitreally 1 microgram of somatuline given once a week for one month, 10 eyes similarly received 5 micrograms/week of somatuline, the remaining 13 eyes serving as controls with intravitreal injections of sterile saline. All animals were examined ophthalmoscopically twice a week for one month in a masked manner, and sacrificed at the end of the experiment for histological and immunohistological analyses. In all but two eyes from the subcutaneously treated group, intravitreal and preretinal membranes formed, five to eight days after platelet injection. Intravitreal proliferation progressively increased, resulting in various degrees of vitreoretinal retraction and retinal detachment.(ABSTRACT TRUNCATED AT 250 WORDS)

MHC class II antigen expression by ocular cells in proliferative diabetic retinopathy.

An immunohistological study was performed on ciliary biopsies of the pars plana obtained surgically in 10 patients suffering from diabetic retinopathy and on 15 surgical specimens of pre-retinal neovascularized membranes. Using immunofluorescence and immunoperoxidase procedures, linear deposits of IgG, IgA and complement components were found in the 8 pars plana from patients with proliferative diabetic retinopathy, at the basal pole of the pigment epithelial cells and within the stroma. In contrast, these deposits were absent from normal pars plana and from the cases of background retinopathy. Moreover, pigment and non-pigment epithelial cells were found to express HLA DR and DQ determinants, in six of the eight patients with proliferative retinopathy. Immunohistological examination of pre-retinal membranes showed deposition of immunoglobulins and complement components within the connective stroma and along the new blood vessels. Endothelial cells of the newly formed vascular walls strongly expressed class II antigens on their membrane, as well as scattered stromal cells. As neither pigment epithelial cells nor retinal vascular endothelial cells normally express class II determinants, our results suggest the involvement of immunological phenomena in intraocular proliferative diseases and eventual interactions between the immune system and peptide growth factors. However, whether or not this immune reaction plays a role in the initiation or extension of intra-ocular proliferation remains to be determined.

HLA DR and DQ distribution in normal human ocular structures.

HLA DR and DQ distribution was investigated in normal human ocular tissues, together with class I antigens and immunocompetent cell subsets, by immunofluorescence and immunoperoxidase procedures. In the anterior segment, our findings, consistent with those of previous reports, showed the wide distribution of class I antigens, specially in the corneal epithelium, while class II antigens were restricted to very rare cells scattered in the conjunctiva, the peripheral cornea and the stroma of the ciliary processes. Some non pigmented epithelial cells of the ciliary processes were HLA DR and DQ positive. In the posterior segment, class I antigens were abundantly represented in the choroid and the retinal layers. Few HLA DR and DQ positive cells were seen in the choroid, similar to those found in the anterior segment. Normal RPE did not react with any monoclonal antibody, but numerous cells located in the retina were strongly HLA DR and DQ positive, all around the blood vessels, and not at the sites of endothelial cells. The characterization of those cells, which could be hypothetized as pericytes needs further studies but suggests close relationships between neuroretina and the immune system. This study may provide insight in the implication of the immune system in many poorly understood ocular diseases.

Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface.

PURPOSE: Long term use of topical drugs has clearly been shown to induce toxic immunopathological changes in the ocular surface. However, little is known concerning the respective roles of active compounds and preservatives. Benzalkonium chloride (BAC) is the most used preservative and its cytotoxicity is well known, but other preservatives have not yet been clearly evaluated. We thus performed a comparative study to investigate toxic side effects induced in the rat ocular surface by applications of various preservatives, with special attention to inflammatory infiltrates. METHODS: A total of 35 brown Norway rats were divided into seven groups of five each. They received, for one month, in both eyes, either 0.01% cetrimonium chloride, 0.01% benzalkonium chloride, 0.01% benzododecinium bromide, 0.004% thiomersal, 0.05% methyl parahydroxybenzoate or phosphate-buffered saline (PBS), the last group remaining untreated. Then, animals were sacrificed and eyes were processed for histological and immunological procedures with monoclonal antibodies to rat immunocompetent cells. RESULTS: When compared to controls, all preservative-treated eyes consistently showed corneal and conjunctival damage, including epithelial alterations, various degrees of keratinization and inflammatory infiltrates at the limbus and within the conjunctival stroma and epithelium. No difference was found between the five tested drugs. CONCLUSIONS: This study confirms that most preservatives used in ophthalmic eyedrops may similarly induce strong histopathological and inflammatory changes in the ocular surface after short term use. Although obtained in animal model, these results confirm strong toxic side effects in patients with preexisting ocular surface disorders and/or receiving topical drugs for long periods.

Multinucleated giant cells in periretinal silicone granulomas are associated with progressive proliferative vitreoretinopathy.

PURPOSE: To determine the histologic features of granulomatous reactions in persilicone periretinal proliferation. PATIENTS AND METHODS: This retrospective study included 12 patients with recurrent retinal detachment and persilicone granulomatous proliferation after vitrectomy for proliferative vitreoretinopathy (PVR). All patients underwent reoperation for membrane surgery. Immunohistochemical study of the excised periretinal membranes was performed with cytokeratins, GFAP, vimentin, CD68, CD45, and lysozyme antibodies. RESULTS: The cellular characteristics of periretinal granulomas allow differentiation of two types of tissue. Spongy tissue (nine cases) showed an accumulation of mature vacuolated macrophages that contained silicone without multinucleated giant cells (MGC). The second type (three cases) consisted of an accumulation of sparsely vacuolated macrophages, epithelioid cells, and MGC. The MGC corresponded to transition forms of foreign body giant cells (FBGC). Spongy tissue was associated with anatomic success (58.3% of cases) and with stabilized PVR (66.7% of cases) at the time of the membrane surgery. MGC were associated with prolonged silicone oil tamponade, recurrent retinal detachment, and progressive PVR. CONCLUSIONS: Intraocular silicone oil can lead to periretinal foreign body granulomas. FBGC are occasionally observed and were associated with progressive PVR.

Immunohistological study of subretinal membranes in age-related macular degeneration.

An immunohistological study was performed on 6 specimens of subretinal membranes obtained surgically from patients suffering from age-related disciform macular degeneration. using immunoperoxidase procedures, we found in those membranes large amounts of IgG, IgA and IgE as well as C1q, C3c and C3d complement components diffusely distributed in the connective stroma and within the new blood vessel walls. Moreover, subretinal membranes contained numerous isolated HLA-DR- and -DQ-expressing cells, including glial, pigment epithelial and vascular endothelial cells. Monoclonal antibodies to immunocompetent cells disclosed only rare B and natural killer lymphocytes or suppressor-cytotoxic T cells, as well as some monocytes. These results show that immune phenomena are involved in proliferative changes associated with subretinal neovascularization. In addition, they suggest there are interactions between the immune system and peptide growth factors.

[The role of surgery in the treatment of age-related macular degeneration]. / Place de la chirurgie dans le traitement de la DMLA.

The place of surgery in DMLA amounts to the surgical treatment of choroidal neovascular membranes and submacular hemorrhage. After a brief historical review, the different techniques currently used are described, but indications have become rarer since the development of dynamic phototherapy. However, despite a high complication rate, these surgical methods should not disappear from our therapeutic arsenal because they have proved their ability to restore good visual acuity.