[Corneal findings in Fabry disease-related keratopathy using in vivo confocal microscopy]. / Evaluation d'une atteinte cornéenne dans le cadre d'une maladie de Fabry par microscopie confocale.

AIM: Description of corneal findings in Fabry disease-related keratopathy using in vivo confocal microscopy. OBSERVATION: A 65-year-old man presenting with a cerebral ischemic lesion was referred to our clinic for ophthalmologic evaluation with a suspicion of inaugural Fabry disease. Slit lamp biomicroscopy showed whorl-like lines in the inferior cornea of both eyes. In vivo confocal microscopy revealed the presence of numerous hyperreflective intracellular inclusions in the corneal epithelium and stroma. DISCUSSION: The whorl-like lines are related to deposition and accumulation of glycosphingolipids in the epithelial and stromal layers of the cornea. This case is also interesting for the late manifestation of Fabry disease, showing the variability in the expression of this condition. CONCLUSION: In vivo confocal microscopy may be an important tool in the follow-up of Fabry disease-related keratopathy, enabling us to monitor the effect of enzyme replacement therapy.

[OCT Visante observation of the progression of a perforated neurotrophic cornea ulcer treated with amniotic membrane grafts]. / Observation à l'OCT Visante de l'évolution d'un ulcère cornéen neurotrophique perforant traité par greffes de membranes amniotiques.

INTRODUCTION: The optical coherence tomography (OCT) Visante provides easy, high-resolution observation free of contact with the cornea and anterior segment. We present the progression of a neurotrophic corneal ulcer treated with amniotic membrane grafts studied with this system. METHODS: A 71-year-old patient with facial nerve paresis secondary to vestibular schwannoma surgery presented with a neurotrophic perforated corneal ulcer. Since medical treatment had failed, we performed an amniotic membrane graft. The OCT Visante was used for follow-up for 2 months. RESULTS: Progression was slow but the perforation eventually closed. Cicatrization of the corneal ulcer was followed with the OCT Visante to document the healing process and corneal thickness. CONCLUSION: Optical coherence tomography Visante provides easy visualization and high-resolution documentation with no contact with the healing corneal ulcerations.

[Evaluation of the anterior chamber depth after cataract surgery with OCT Visante]. / Evaluation de la profondeur de la chambre antérieure après chirurgie de la cataracte avec l'OCT Visante.

INTRODUCTION: OCT Visante allows the visualisation of the anterior segment structures and particularly of the irido-corneal angle by a non-contact method. We made a prospective study on 14 patients to demonstrate by OCT Visante the changes of irido-corneal angle and depth of the anterior chamber after cataract surgery. PATIENTS AND METHODS: 14 eyes of 14 patients have undergone a phacoemulsification of the cataract with posterior chamber lens implantation. All patients have had a complete ophthalmologic examination, an OCT Visante with angle measurement and an A-Scan for determination of the lens thickness. All these exams were repeated at 1 week and 1 month postoperatively. RESULTS: In all patients, we noticed an increase of the postoperative iridocorneal angle. The mean preoperative angle was 18.3 degrees +/- 11.81 SD, 38.65 degrees +/- 3.95 SD at 1 week postoperatively and 45.7 degrees +/- 8.72 SD at 1 month. DISCUSSION: Imagery by OCT Visante allowed us by a non-invasive method to quantify very precisely the opening of the irido-corneal angle and the increase of the anterior chamber depth after cataract surgery. OCT Visante is a method allowing the visualisation and quantification of anterior segment changes after cataract surgery.

Autologous serum application in the treatment of Mooren's ulcer.

BACKGROUND: Mooren's ulcer is a peripheral corneal ulceration of presumed autoimmune aetiology. Its clinical course and eventual prognosis is variable and usually these ulcers respond poorly to conventional therapy. HISTORY AND SIGNS: A 67-year-old male was referred to our hospital for a painful, red and tearing left eye after receiving debris. Slit-lamp examination revealed a 3.2 x 2.1 mm peripheral corneal ulcer, a diffuse thinning of the lateral limbus (between 3 o'clock and 5 o'clock) and some endothelial precipitates. The conjunctiva was severely congested. In the anterior chamber, cells (++) and fibrin were found. THERAPY AND OUTCOME: We introduced an antibiotic, corticosteroid and cyclosporin therapy to treat the marginal corneal deficit caused by Mooren's ulcer. The patient did not respond to the initial treatment, but re-epithelialisation occurred and the corneal deficit improved after the introduction of autologous serum eye drops. CONCLUSION: Autologous serum seems to be an effective supplementary therapy in Mooren's ulcer.

Ultrastructural alterations in capillaries of the diabetic hypertensive rat retina: protective effects of ACE inhibition.

AIMS/HYPOTHESIS: The ACE inhibitor cilazapril was administered to diabetic hypertensive rats to evaluate its ability to influence the development of retinal capillary alterations. METHODS: Normotensive (strain: Wistar Kyoto) and genetically hypertensive (strain: spontaneously hypertensive) rats were rendered diabetic by intravenous injections of streptozotocin. Half of the diabetic animals received cilazapril with their daily food. At 20 weeks of diabetes, endothelial cells, pericytes and extracellular matrix were assessed by ultrastructural morphometry. Each experimental group consisted of seven animals. RESULTS: Cilazapril normalised systolic arterial pressure in diabetic hypertensive rats (137+/-2 mm Hg compared with 188+/-16 mm Hg in non-medicated diabetic hypertensive rats, p<0.001). The number of endothelial intercellular junctions was reduced in untreated diabetic hypertensive rats (0.15+/-0.05, p<0.02, vs 0.47+/-0.20 in non-diabetic normotensive rats). In diabetic hypertensive animals treated with cilazapril, this loss was attenuated (0.32+/-0.16, p<0.05). The significant thickening of the basement membrane observed in the diabetic normotensive (132.8+/-19.4 nm) and diabetic hypertensive (150.3+/-20.2 nm) groups was decreased by cilazapril in the diabetic hypertensive group (116.7+/-11.0 nm, p<0.01), but was unaffected in the normotensive (131.9+/-17.3 nm) group. No protective effect of the drug was observed in either group on pericytes. CONCLUSIONS/INTERPRETATION: Long-term administration of an effective antihypertensive therapy normalises endothelial alterations and basement membrane thickness in diabetic hypertensive conditions, and thus may account for the well-known improvement of the blood-retinal barrier observed during antihypertensive treatment.

Glial reactivity, an early feature of diabetic retinopathy.

PURPOSE: To characterize early structural gliotic reactions in retinal Müller cells, astrocytes, and microglia in experimentally induced diabetes. METHODS: Rats were rendered diabetic by streptozotocin injection and killed after 2, 4, 12, or 20 weeks. Cell densities were determined in flatmounted retinas or transverse semithin sections. Expression of glial fibrillary acidic protein (GFAP) was localized on frozen sections or flatmounts by immunofluorescence and confocal microscopy, and GFAP content was evaluated by Western blot analysis. Microglial cells were visualized by binding of isolectin B4 or staining with antibodies to phosphotyrosine residues. The integrity of the blood-retinal barrier was assessed by intravenous injection of Evans blue. RESULTS: The density of Müller cells and microglia was significantly increased at 4 weeks of diabetes compared with nondiabetic controls. GFAP expression in Müller cells was not detected at 4 weeks but was prominent at 12 weeks. The number of astrocytes was significantly reduced at 4 weeks in the peripapillary and far peripheral retina. Shape changes of microglial cells indicated functional activation. Leakage of the blood-retinal barrier was observed at 2 weeks of hyperglycemia, the earliest time point investigated. CONCLUSIONS: The leakage of the blood-retinal barrier before glial reactivity suggests that glia are early targets of vascular hyperpermeability. The individual glial cell types react differentially to the diabetic state. Müller cells undergo hyperplasia preceding GFAP expression, and microglial cells are activated, whereas astrocytes regress. This glial behavior may contribute decisively to the onset and development of neuropathy in the diabetic retina.

Remodeling of retinal capillaries in the diabetic hypertensive rat.

PURPOSE: To document the effect of sustained systemic hypertension on the integrity and ultrastructural morphology of retinal capillaries in diabetic and nondiabetic rats. METHODS: Normotensive (strain Wistar-Kyoto; WKY) and genetically hypertensive (spontaneously hypertensive; SHR) rats were rendered diabetic by intravenous streptozotocin injection. At 20 weeks of diabetes, endothelial cells, pericytes, and extracellular matrix were evaluated by ultrastructural morphometry. Serum albumin was localized by immunofluorescence microscopy. RESULTS: The endothelial cell layer was markedly thinner in the diabetic normotensive animals. The number of intercellular junctions was reduced in both the nondiabetic and diabetic hypertensive group but less so in the diabetic normotensive group. No significant endothelial cell loss was noted in either of the experimental groups, whereas the number of pericytes and the number of their cytoplasmic processes were reduced in diabetic and hypertensive animals. Significant thickening of the basement membrane and increased permeability to serum albumin were observed in diabetic and hypertensive rats and were strongly enhanced in the combined diseases. CONCLUSIONS: Endothelial thinning and shape changes from an elaborate to a simpler form as well as rounding up of the pericytes and loosening of their vascular sheaths indicate remodeling of the vascular wall during chronic diabetes and sustained hypertension, before a characteristic vasculopathy becomes manifest. The combination of diabetes and hypertension enhances these features, as well as basement membrane thickening and breakdown of the blood-retinal barrier.

Contrast sensitivity in obese dyslipidemic patients with insulin resistance.

OBJECTIVE: To evaluate contrast sensitivity in insulin-resistant obese patients and in aretinopathic diabetic patients. METHODS: Contrast sensitivity was measured at 3 letter sizes (44 x 44, 9 x 9, and 5 x 5 mm) in mesopic (5 candela [cd]/m2) and low photopic (85 cd/m2) vision in 20 dyslipidemic obese patients with insulin resistance, 20 age-matched patients with type 2 diabetes mellitus, and 20 aged-matched healthy control subjects. RESULTS: Significant loss of contrast sensitivity at all 3 letter sizes was observed in low photopic vision (at 44 x 44-mm letter size, control vs obese, P<.002, and control vs diabetic, P<.005; at 9 x 9-mm letter size, control vs obese, P<.02, and control vs diabetic, P<.001; and at 5 x 5-mm letter size, control vs obese, P<.05, and control vs diabetic, P<.005) and mesopic vision (at 44 x 44-mm letter size, control vs diabetic, P<.005; at 9 x 9-mm letter size, control vs obese, P<.005, and control vs diabetic, P<.01; and at 5 x 5-mm letter size, control vs obese, P<.005, and control vs diabetic, P<.001) in insulin-resistant obese and diabetic patients. CONCLUSION: The results suggest that an early neurosensory dysfunction may occur without visible vascular involvement and without overt hyperglycemia.

Exfoliation syndrome and phacoemulsification.

PURPOSE: To evaluate intraoperative and postoperative complications of phacoemulsification and intraocular lens (IOL) implantation in eyes with exfoliation syndrome. SETTING: Eye Clinic, University Hospital of Geneva, Switzerland. METHODS: This prospective study evaluated 20 consecutive patients with exfoliation syndrome and 20 consecutive patients without the syndrome (control group) who had phacoemulsification and posterior chamber IOL implantation. One year later, the incidence of zonular tears, operating time, and fibrinoid reaction were studied in another group of 23 consecutive patients who had the same type of surgery by the same surgeon. RESULTS: Maximal pupil dilation was significantly smaller (P < .0001) in the exfoliation than in the control group. Intraoperatively, the incidence of zonular tears was the same in both groups (10%). In the 23 patients who had surgery 1 year later, no zonular tears occurred. The incidence of postoperative complications was similar in both groups. The exfoliation group had a significant decrease in intraocular pressure over preoperative levels at 1 week and 3 months postoperatively. CONCLUSION: Phacoemulsification with posterior chamber IOL implantation appears to be safe in eyes with exfoliation syndrome.

Risk factors associated with contrast sensitivity loss in diabetic patients.

BACKGROUND: Psychophysical tests in patients with diabetes mellitus reveal deficits of central vision before the development of overt retinopathy. We evaluated the contrast sensitivity thresholds in 30 patients with type II diabetes mellitus and without retinopathy, taking into account the crystalline lens density. Risk factors for contrast sensitivity deficits were investigated. METHODS: Contrast sensitivity was compared in 30 aretinopathic diabetic patients and age-matched controls. Contrast thresholds were determined for stationary gratings at three spatial frequencies (6, 15, and 27 cycles/deg) and for mesopic (5 cd/m2) and low photopic (85 cd/m2) vision. Lens density was measured using a IntraOptics opacity lensmeter. RESULTS: Significant contrast sensitivity losses at all three spatial frequencies were observed in low photopic and mesopic vision in diabetic patients. The optical density of the lens in the diabetic group did not differ from that in the controls. Contrast sensitivity deficits were positively correlated with patient's age, systolic blood pressure and nephropathy at all three spatial frequencies. No relationship between cardiovascular autonomic neuropathy and contrast sensitivity defects was observed. CONCLUSIONS: These data suggest that contrast sensitivity deficits in diabetic patients without retinopathy are not solely explained by a diabetes-induced increases in lens optical density. Abnormalities of the retina or its neural connections occurring before the onset of clinically detectable retinopathy may be involved. Risk factors for these deficits are advanced age, high systolic blood pressure, and nephropathy.

[Effectiveness of treatment of diabetic macular edema by laser photocoagulation]. / Efficacité du traitement de l'oedème maculaire diabétique par photocoagulation au laser.

BACKGROUND: Diabetic macular edema is the most frequent cause of visual loss in patients with diabetic retinopathy. Laser photocoagulation of clinically significant macular edema is effective in reducing the risk of visual loss. METHODS AND RESULTS: Sixty three eyes of 42 diabetic patients with macular edema were included in a clinical study to determine the short-term visual outcome (9 months) of laser photocoagulation. The results suggest that laser photocoagulation is less effective in diabetic patients with high blood pressure and in patients with low visual acuity at treatment time.

[Diagnostic aspects and frequency of retrocorneal precipitates in diagnosis of cytomegalovirus retinitis in the HIV+ patient]. / Aspect et fréquence des précipités rétrocornéens lors du diagnostic de la rétinite à CMV chez le patient VIH+.

Cytomegalovirus retinitis (CMV) is the most common ocular opportunistic infection seen in patients with acquired immune deficiency syndrome. The anterior segment is usually quiet or with minimal aqueous humour flare and cell reaction. Nevertheless, in this prospective study of 30 eyes with CMV retinitis, 22 (73%) had white, small and filamentous keratic precipitates (KPS) which seem to corroborate this inflammation. The positivity of the KPS depends upon the extent of CMV retinitis.

[Occlusion of the ophthalmic artery in Crohn disease]. / Occlusion de l'artère ophtalmique dans la maladie de Crohn.

BACKGROUND: Nearly 10% of patients with Crohn's disease develop ocular complications. Most complications are inflammatory in nature, and involve both the anterior and the posterior segments of the eye. Episcleritis, uveitis and keratopathies are the most frequently described. Occlusions of retinal and optic nerve vessel are less common. We believe this to be an important observation as the ocular involvement was the patients primary complaint, thus allowing the correct diagnosis to be made. PATIENT: We report a case of a 44-year-old woman, who presented with an occlusion of the ophthalmic artery, before the diagnose of Crohn's disease was established.

Growth of bovine retinal pericytes and endothelial cells in high hexose concentrations.

Selective loss of capillary pericytes occurs early in diabetic and galactosemic retinopathies, at a stage when endothelial cells are still spared. To ascertain whether such loss is directly related to high hexose concentrations, the replication of bovine retinal pericytes and endothelial cells was studied by culturing them in media containing 5.6 mmol/l glucose alone and enriched with extra glucose, mannitol or galactose to achieve final concentrations of 16.7, 27.8 and 50.0 mmol/l. At the end of the incubation there were significantly less pericytes/culture cell in 16.7 mmol/l glucose (341 +/- 78 x 10(3), mean +/- SEM, p = 0.027) and galactose (304 +/- 55 x 10(3), p = 0.046) than in 5.6 mmol/l glucose (417 +/- 98 and 355 +/- 75 x 10(3) for separate experiments, respectively). Mannitol had no such effect (343 +/- 52 vs. 337 +/- 52 x 10(3). Endothelial cells did not change in number, except in 50.0 mmol/l glucose (533 +/- 66 vs. 629 +/- 67 x 10(3) at 5.6 mmol/l; p = 0.026) and 50.0 mmol/l galactose (440 +/- 48 vs. 592 +/- 51 x 10(3); p = 0.013). To verify if these effects are due to decreased replication, the uptake of 3H-thymidine was measured in pericytes and endothelial cells subjected to the same concentrations of glucose, mannitol and galactose. In pericytes, thymidine uptake was reduced in the presence of 16.7 mmol/l glucose (p = 0.003, compared to 5.6 mmol/l) and galactose (p = 0.027) but not mannitol. Pericyte counts and thymidine uptake was reduced for concentrations of glucose, galactose and mannitol higher than 16.7 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diabetic maculopathy: clinical aspects, risk factors and therapeutic possibilities]. / La maculopathie diabétique: aspects cliniques, facteurs de risque et possibilités thérapeutiques.

Edema of the macula is a frequent component of diabetic retinopathy, as well as a common cause of visual impairment in this disorder. It is strongly associated with high blood pressure and the presence of proteinuria. Correction of these risk factors may reduce macular edema and should be included as part of the total management of patients with diabetic maculopathy. The benefit of a focal treatment for focal macular edema has been established but the results are not so good when a grid treatment for diffuse macular edema is performed.

Pericyte mitogenic activity is reduced in the blood of type 1 diabetic patients with and without retinopathy.

Selective loss of capillary pericytes occurs early and specifically in diabetic retinopathy. We have investigated whether blood derivatives from patients with long-term type 1 (insulin-dependent) diabetes and no retinopathy differ from those with retinopathy and/or non-diabetic controls in their ability to stimulate DNA synthesis in cultured bovine retinal pericytes and endothelial cells. As a general trend, whole blood serum, platelet-rich plasma and platelet-free plasma from patients without and with retinopathy stimulated thymidine incorporation in both cell types less than derivatives from controls. Serum, 0.1% v/v final concentration in culture medium, from patients without retinopathy was less active (114.5 +/- 24.5% of a standard stimulus produced by 0.1% fetal calf serum) than that from patients with the complication (132.6 +/- 20.8%, P = 0.003) and both were less potent than control sera (143.6 +/- 28.0%, P < 0.001 and P = 0.013, respectively). Lack of support from circulating factor(s) may contribute to the disappearance of pericytes from the capillary wall in diabetes but further investigations are necessary to clarify the mechanisms that prevent the development of microangiopathy in some patients.

A study of the effects of human blood derivatives and individual growth factors on [3H]thymidine uptake in bovine retinal pericytes and endothelial cells.

Pericytes disappear early, selectively and specifically from retinal capillaries in diabetic microangiopathy, but little is known of their growth and turnover in health and disease. We have studied the effects of human blood derivatives and of a panel of individual growth factors on [3H]thymidine incorporation in bovine retinal pericytes and endothelial cells. Human serum and platelet-rich plasma stimulated incorporation of the nucleotide in a dose-dependent manner in both cell types, and did so more potently than platelet-free plasma. Consistent and significant stimulation of DNA synthesis in pericytes was observed with basic fibroblast growth factor (ED50 = 1.8 x 10(-13) mol/l), acidic fibroblast growth factor (7.4 x 10(-12) mol/l), insulin-like growth factor 1 (8.6 x 10(-10) mol/l), insulin (158 microU/ml) and endothelin-1 (6.1 x 10(-10) mol/l). Transforming growth factor beta 1 inhibited DNA synthesis (ID50 = 3.6 x 10(-10) mol/l) and so did heparin (1.4 x 10(-6) mol/l) and low molecular weight heparin (2.9 x 10(-6) mol/l). Retinal endothelial cells were stimulated by basic fibroblast growth factor (3.2 x 10(-13) mol/l) and acidic fibroblast growth factor (1.3 x 10(-9) mol/l), and inhibited by transforming growth factor beta 1 (1.6 x 10(-12) mol/l). Neither cell type was stimulated by platelet-derived growth factor (A + B chain heterodimer), epidermal growth factor, growth hormone, or nerve growth factor (7S complex). The characteristics and active concentrations of the above growth factors suggest that none is solely responsible for the pericyte mitogenic activity of platelets, serum or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Monozygotic twin brothers with age-related macular degeneration.

We report the simultaneous development of exudative macular degeneration in monozygotic twin brothers. This report supports the hypothesis that genetic factors may be implicated in the pathogenesis of age-related macular degeneration.