Expression of antiapoptotic and proapoptotic molecules in diabetic retinas.

PURPOSE: To investigate the expression of the antiapoptotic and proapoptotic markers in diabetic retinas. METHODS: In total, 12 donor eyes from six subjects with diabetes mellitus, and 10 eyes from five nondiabetic subjects without known ocular disease serving as control subjects were examined. Immunohistochemical techniques were used with antibodies directed against cyclooxygenase-2 (Cox-2), Akt (protein kinase B), Mcl-1, Bad, cytochrome c, apoptosis-inducing factor (AIF), tumour necrosis factor receptor-1-associated death domain protein (TRADD), and Fas-associated death domain protein (FADD). RESULTS: In retinas from all subjects without diabetes, cytoplasmic immunoreactivity for the antiapoptotic molecules Cox-2, Akt, and Mcl-1 was noted in ganglion cells. Cytoplasmic immunostaining for Cox-2 was also noted in the retinal pigment epithelial cells. Weak immunoreactivity for the mitochondrial apoptogenic proteins cytochrome c, and AIF was noted in the inner segments of photoreceptors, in the inner one-third of the outer plexiform layer, in cells in the inner nuclear layer, in the inner plexiform layer, and in ganglion cells. There was no immunoreactivity for the other antibodies tested. All diabetic retinas showed de novocytoplasmic immunoreactivity for Bad in ganglion cells, and in occasional cells in the inner nuclear layer. Upregulation of cytochrome cand AIF immunoreactivity was noted. Cox-2, Akt, and Mcl-1 immunoreactivity was not altered in the diabetic retinas. There was no immunoreactivity for TRADD, and FADD. CONCLUSIONS: Ganglion cells in diabetic and nondiabetic retinas express the antiapoptotic molecules Cox-2, Akt, and Mcl-1. Retinal ganglion cells express the proapoptotic molecule Bad in response to diabetes-induced neuronal injury. Diabetic retinas show upregulation of the mitochondrial proteins cytochrome c, and AIF.

Inducible nitric oxide synthase and vascular endothelial growth factor are colocalized in the retinas of human subjects with diabetes.

PURPOSE: Nitric oxide (NO) mediates vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability. This study was undertaken to study the cellular distribution of inducible nitric oxide synthase (iNOS) and VEGF in the retinas from human subjects with diabetes mellitus. In addition, glial reactivity and peroxynitrite generation were detected by immunolocalization of glial fibrillary acidic protein (GFAP) and nitrotyrosine, respectively. METHODS: Eight post-mortem eyes from four consecutive subjects with diabetes mellitus and eight eyes from four subjects without diabetes and without known ocular disease were prospectively collected and examined. We used immunohistochemical techniques and antibodies directed against iNOS, VEGF, GFAP, and nitrotyrosine. RESULTS: In retinas from all subjects without diabetes, weak GFAP immunoreactivity was confined to nerve fibre and ganglion cell layers. There was no immunoreactivity for iNOS, nitrotyrosine, and VEGF. All diabetic retinas showed GFAP induction in Müller cells and GFAP upregulation in nerve fibre and ganglion cell layers. All diabetic retinas showed cytoplasmic immunoreactivity for iNOS, and VEGF in ganglion cells, cells in the inner nuclear layer, and glial cells. In serial sections, ganglion cells and cells in the inner nuclear layer expressing VEGF were localized in the same area of iNOS-expressing ganglion cells and cells in the inner nuclear layer. Six retinas from three subjects with diabetes showed immunoreactivity for nitrotyrosine in vascular endothelial cells in inner retinal layer. CONCLUSIONS: iNOS and VEGF are colocalized in diabetic retinas. Increased GFAP immunoreactivity is a pathological event in the retina during diabetes.

Color vision in 42 Congolese patients with tuberculosis receiving ethambutol treatment.

PURPOSE: To study color vision in Congolese patients with tuberculosis receiving ethambutol therapy. METHODS: A prospective, descriptive study of color vision test in patients with systemic tuberculosis receiving ethambutol was performed between April 1995 and January 1998 at the Department of Ophthalmology, University of Kinshasa. Color vision tests were assessed with pseudoisochromatic plates (the Ishihara Pseudo-isochromatic Plates), the AO-HRR (American Optical Handy Rand Rittler), the Bölle and Kastel anomaloscope, Farnsworth-Munsell test (the D-15 and the FM-100). RESULTS: There were 42 patients with a mean age of 33 years (range, 14 to 75 years). The color vision of all the patients was found to be normal as measured by the Ishihara pseudoisochromatic plates. One (2%) patient showed color vision defect (anarchic axis] with the OA-HRR test. Three (7%) of 42 patients displayed blue-yellow color axis or anarchic axis color vision test on the D-15 test. Fifteen (36%) of 42 patients had high total error scores at the Farnsworth-Munsell 100 test. The color axis was as follows: anarchic axis (13.1%), red-green-color and blue-yellow-color combined axis (13.1%), blue-yellow color axis (7.5%). Results of the Bölle and Kastel anomaloscope were normal in all patients. CONCLUSION: Our results confirm the importance of color vision examinations in the detection of the complications of ethambutol treatment.

Pitfalls in the diagnosis of craniopharyngioma: 2 case reports.

Two cases of craniopharyngioma with delayed diagnosis are presented. Patient 1 had mild visual loss that initially had been attributed to pigment epithelial detachment in the macular area. Patient 2 had blurred vision in the left eye, although visual acuity was 10/10 at both eyes. She had a history of a posttraumatic neurosurgical procedure and was treated for blepharospasm. Both patients had initially negative CT imaging. Visual field defects suggested a chiasmal lesion and incited to additional neuroradiological investigation. Magnetic resonance imaging revealed a craniopharyngioma in both cases.

Expression of the inducible isoform of nitric oxide synthase in the retinas of human subjects with diabetes mellitus.

PURPOSE: Inducible nitric oxide synthase has been implicated in the pathogenesis of cerebral ischemic damage, in the angiogenic process and in diabetic vascular damage. This study was undertaken to determine whether inducible nitric oxide synthase is present in the retinas from human subjects with diabetes mellitus. METHODS: This was an experimental immunohistochemical prospective study. Ten postmortem eyes from five subjects with diabetes mellitus, 10 eyes from five subjects without diabetes and without known ocular disease, and two eyes from one subject with unilateral ocular ischemic syndrome secondary to severe carotid artery obstruction were examined. We used immunohistochemical techniques and antibodies directed against inducible nitric oxide synthase, glial fibrillary acidic protein, and vimentin. The main outcome measure was immunoreactivity for these antibodies. RESULTS: Immunoreactivity for inducible nitric oxide synthase was not observed in retinas from all subjects without diabetes and without ocular disease. Six retinas from three subjects with diabetes and nonproliferative retinopathy, and the retina from the eye with ocular ischemic syndrome showed immunoreactivity for inducible nitric oxide synthase in cells with elongated processes. Based on morphology and on glial fibrillary acidic protein and vimentin immunoreactivity, this inducible nitric oxide synthase immunoreactivity appeared to localize to retinal Müller glial cells. CONCLUSIONS: These observations suggest that Müller cells may be involved in the microvascular remodeling of the diseased retina and that high concentrations of nitric oxide produced by inducible nitric oxide synthase could contribute to neurotoxicity and angiogenesis that occur in diabetic retinopathy.

Unusual retinal vasculitis in a patient with protein S deficiency and systemic toxoplasmosis: a case report.

A 28-year old female patient presented with unilateral dropped visual acuity and a central scotoma. Fundus examination and a fluorescein angiogram were suggestive for central retinal vein prethrombosis. Further tests revealed an isolated protein S deficiency for which oral anticoagulation therapy was initiated. Six months later she presented with new symptoms of a right retrobulbar pain on ocular movements. The retinal vessels had normalized with improved visual acuity. Re-evaluation of the fluorescein angiogram taken six months earlier showed an image compatible with unilateral vasculitis. During this six month period persisting high levels of IgG and IgM antibodies against Toxoplasma were observed while no signs of other active infection could be found. This report illustrates that in cases of prethrombosis with vasculitis in a young patient, a full medical examination and a thorough investigation of infectious diseases are warranted.

Ocular findings in children with homozygous sickle cell disease in the Democratic Republic of Congo.

OBJECTIVE: The purpose of the study is to determine the frequency of ocular manifestations in Congolese children with homozygous sickle cell disease. METHODS: Sixty-six children with homozygous sickle cell disease were examined for ocular abnormalities between March 1 and August 31, 1998. The ages of children ranged from two to 18 years. Routine ophthalmic examination included measurement of visual acuity, inspection of the adnexa and cornea, refraction, silt-lamp examination and dilated ophthalmoscopy. RESULTS: Ocular abnormalities were found in 47 (71%) children of 66 subjects. Ophthalmologic abnormalities included conjunctival signs (32%), retinal vascular tortuosity (29%) and dilatation (26%), AV crossing (29%). CONCLUSIONS: Ocular findings in this study were similar to those previously published in Africa, which showed a low frequency of retinal changes.

OCT study of fellow eyes of macular holes.

The aim of this study was to examine the vitreomacular interface in symptom-free fellow eyes of macular holes using optical coherence tomography (OCT) to add information to the pathogenesis of macular holes and to refine prognostic factors for bilateral involvement. Sixty-six patients with a full thickness macular hole in one eye and a symptom-free fellow eye were included in the study between 01/98-05/99. The finding on OCT that a perifoveal vitreous detachment can result in a foveal cyst and subsequently a macular hole confirms the theory of Gass of vitreous traction. Symptom-free fellow eyes with a foveal cyst on OCT represent an elevated risk (55%) for macular hole development. Vitreofoveal separation is probably a good prognostic sign.

Treatment of glaucoma in children with Sturge-Weber syndrome.

BACKGROUND: Sturge-Weber syndrome is a rare congenital neuro-oculocutaneous disorder. Ocular involvement can include glaucoma and vascular malformations of the conjunctiva, episclera, choroid, and retina. METHODS: The records of 19 Sturge-Weber syndrome patients (mean age 8.2 years) treated at our institution were reviewed to determine the incidence of ophthalmologic manifestations in Sturge-Weber syndrome. RESULTS: Glaucoma occurred in 42% of all patients and was more frequent in patients with a port-wine stain involving both upper and lower eyelids. Other ocular manifestations included conjunctival/episcleral hemangioma, choroidal hemangioma, iris heterochromia, retinal detachment, strabismus, and homonymous hemianopia. In 7 of 8 patients with glaucoma, topical pharmacotherapy (beta-blockers and carbonic anhydrase inhibitors) alone failed to normalize intraocular pressures. In those patients, cryocoagulation of the ciliary body was performed. Mean postoperative intraocular pressure after a mean follow-up of 4-5 years was <22 mm Hg in 6 patients. CONCLUSIONS: Cryocoagulation of the ciliary body combined with topical medication is an effective and safe treatment option in the management of glaucoma in children with Sturge-Weber syndrome.

Diplopia from skew deviation in Ramsey-Hunt syndrome. A case report.

OBJECT: Presentation of a 34-year-old pregnant woman with skew deviation due to peripheral vestibular dysfunction caused by herpes zoster oticus. METHODS: A multidisciplinary approach (neuroophthalmology, otorhinolaryngology, neuroradiology) revealed the diagnosis of Ramsey-Hunt syndrome. CASE REPORT: The patient presented with painful herpes zoster vesicles of the left ear, associated with a rotatory vertigo and hearing loss. Otorhinolaryngological examination showed a unilateral peripheral vestibular loss, a nystagmus towards the unaffected right side, no facial nerve dysfunction and a left perception hearing loss, mainly in the frequencies between 2-6 KHz. The patient was treated with Zovirax IV. Neuroradiological examination (MRI without contrast) revealed no abnormalities. Vertical diplopia from skew deviation was noted +/- 10 days after onset of herpes zoster oticus. Neuroophthalmological and orthoptic examination showed a comitant right hypertropia of 6 diopters and a spontaneous nystagmus to the right. CONCLUSION: Skew deviation can be caused by a sudden unilateral cochleo-vestibular loss as described by A.B. Safran. (4,6,7,8).

The use of optical coherence tomography in macular diseases.

With optical coherence tomography (OCT), a new technique has emerged that allows imaging of a transverse section of the retina with a resolution that has not been reached by other imaging techniques. The OCT technique can be used in the diagnosis and assessment of various diseases of both the anterior segment and the ocular fundus. This paper demonstrates that OCT can deliver useful information in the diagnosis and follow-up of several macular diseases that cannot be obtained with other fundus imaging techniques. The optical principle of OCT is based on visible-light interference. OCT allows imaging of the anatomical foveal appearance. This normal foveal appearance is disrupted when macular edema occurs, leading to thickening of the neuroretina and cyst formation. The anatomical difference between a neuro-retinal elevation and RPE elevations can be demonstrated using OCT. Epiretinal membranes and pseudo-macular holes can easily be visualized. Perhaps the most interesting addition of OCT in the retinal diagnostic field is the imaging of vitreo-macular traction syndromes and staging of macular holes, which are both difficult with ophthalmoscopy and fluorescein-angiography. Each of the above mentioned macular diseases will be illustrated by a typical case.

How to protect your eyes from solar retinopathy.

On August 11, in Belgium a solar eclipse will occur which will be total in the Southern area of the country. Although the observation of a solar eclipse is an intriguing phenomenon, inappropriate shielding from the sunlight can cause irreversible ocular lesions. Besides good absolute absorption of visible light, a blocking of ultraviolet and infrared light is equally important. In this study, four homemade sun filters were tested: a soot-blackened piece of glass, a black unexposed developed slide film, an audio-CD and a recordable CD-ROM. Also two commercially available filters were investigated: eclipse-shades and mylar foil. The soot-blackened glass and black slide film slip were highly transparent for infrared light, making them dangerous for solar observation. The recordable CD-ROM was too transparent for visible light to serve as solar filter, while the audio-CD tested absorbed enough visible, ultraviolet and infrared light to make it suitable for eclipse viewing. However, many types of audio-CD's are available making it impossible for the observer to know if a given CD is safe to use for solar viewing. Both commercially available solar filters tested had a good absolute visible light absorption, as well as an equally good absorption of ultraviolet and infrared light, making them safe for eclipse observation.

Gelatinase B in proliferative vitreoretinal disorders.

PURPOSE: To investigate whether gelatinases A and B are involved in the pathogenesis of proliferative vitreoretinal disorders. METHODS: In a prospective study of 101 consecutive patients, vitreous and paired serum samples were obtained from 38 patients with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy, 25 patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy, and 38 patients with proliferative diabetic retinopathy. Gelatinase activities were determined by quantitative zymography. RESULTS: All vitreous samples contained comparable levels of the constitutive gelatinase A. Inducible gelatinase B was detected in eight (32%) of 25 vitreous samples from patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy (mean +/- SD, 319.5 +/- 521.0 scanning units), in 17 (44.7%) of 38 vitreous samples from patients with proliferative vitreoretinopathy (560.6 +/- 718.9 scanning units), and in 34 (89.5%) of 38 vitreous samples from patients with proliferative diabetic retinopathy (1,707.2 +/- 1,220.3 scanning units). The incidence of detection of gelatinase B in proliferative diabetic retinopathy cases was significantly higher than it was in rhegmatogenous retinal detachment with no proliferative vitreoretinopathy and proliferative vitreoretinopathy cases (P < .001). Gelatinase B levels in the vitreous samples of patients with proliferative diabetic retinopathy were higher than the levels found in patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy and in patients with proliferative vitreoretinopathy (P = .0152). Gelatinase A was detected in all the tested sera, whereas none of the tested paired serum samples contained detectable gelatinase B activity. CONCLUSIONS: Gelatinase B may play an important role in extracellular matrix degradation associated with neovascularization in proliferative diabetic retinopathy.

Monocyte chemotactic protein-1 in proliferative vitreoretinal disorders.

PURPOSE: To investigate whether the chemokines monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) are involved in the pathogenesis of proliferative vitreoretinal disorders and to study their possible interaction with IL-6. METHODS: In a prospective study of 125 consecutive patients (125 eyes), vitreous and paired serum samples were obtained and were assayed for MCP-1 and IL-8. Levels of IL-6 were determined by proliferation of the IL-6-dependent hybridoma cell line 7TD1. RESULTS: Monocyte chemotactic protein-1 was detected in 13 (48%) of 27 vitreous samples from patients with retinal detachment, in five (63%) of eight samples from patients with macular pucker, in 31 (72%) of 43 samples from patients with proliferative vitreoretinopathy, and in 32 (76%) of 42 samples from patients with proliferative diabetic retinopathy, but not in samples from five patients with idiopathic epiretinal membrane. There was a significant (P = .049) correlation between the incidence of MCP-1 detection in retinal detachment, macular pucker, and proliferative vitreoretinopathy groups and the severity of proliferation. Interleukin-8 was detected in two vitreous samples from eyes with retinal detachment, in two samples from eyes with proliferative vitreoretinopathy, and in three samples from eyes with proliferative diabetic retinopathy. Monocyte chemotactic protein-1 levels in the vitreous samples were positively correlated with IL-6 levels (r = .31, P = .01). Interleukin-6 levels were significantly (P = .0097) greater in vitreous samples with than without detectable levels of MCP-1. CONCLUSION: Monocyte chemotactic protein-1 is present in a substantial percent of vitreous samples from eyes with proliferative vitreoretinal disorders and may help in stimulating the infiltration of monocytes and macrophages into eyes with these disorders.

Spontaneous evolution of stage I and II macular holes.

To ascertain the natural outcome of stage I impending and stage II macular holes, 28 eyes (26 patients) were reviewed and followed up for an average of 23 months. Of the 21 stage I lesions, 10 (47.6%) progressed and the others regressed. In the stage II group (9 eyes), 5 lesions (55.5%) progressed, 2 (22.2%) regressed and 2 (22.2%) remained stable during a follow-up period of 7.75 months. Patients with stage II macular holes seem to be more likely to benefit from surgery than patients with stage I lesions. However, even in stage II macular holes, regression may be observed and the possible benefit from surgery must be weighed against the known complications and risk factors.

Leber congenital amaurosis--differential diagnosis, ophthalmological and neuroradiological report of 18 patients.

Between 1985 and 1995 eighteen babies, presenting to our department with absent visual contact and roving eye movements, showed a non-recordable flash electroretinogram (fERG). This was confirmed when repeated after a one-year interval. In four patients with developmental delay an underlying systemic disorder was diagnosed after a thorough pediatric neurological evaluation: Senior Loken syndrome, neuroaxonal dystrophy, ceroid lipofuscinosis and a yet unclear metabolic disorder were the revised diagnoses. The fourteen remaining patients were diagnosed as having primary idiopathic Leber Congenital Amaurosis (LCA). Three of them showed developmental delay. In all three cerebellar abnormalities were visualized on brain computed tomography (CT) and/or magnetic resonance imaging (MRI). Brain CT of the other eleven patients with age appropriate development was normal. We conclude that LCA is a diagnosis of exclusion and a cautious approach with a thorough history and pediatric neurological examination is necessary to exclude a more global pediatric neurological disorder.

Bromovinyldeoxyurdine treatment of outer retinal necrosis due to varicella-zoster virus: a case-report.

In December 1995, a 70-years old male was referred to us because of rapid visual loss in the right eye, one month after a central retinal artery occlusion in the left eye. This renal transplant patient, with limited renal function, was on immunosuppressive therapy. The diagnosis of bilateral progressive outer retinal necrosis (PORN) due to varicella-zoster virus (VZV) was confirmed by polymerase chain reaction (PCR) detection of VZV DNA in the aqueous fluid. As retinitis progressed despite of intravenous acyclovir administration, the antiviral therapy was switched to oral bromovinyldeoxyuridine (BVDU). This case-report demonstrates that oral BVDU can be a good alternative to acyclovir for the treatment of VZV retinal infections.

Management of psoteriorly dislocated crystalline lenses or lens fragments.

The authors conducted a retrospective study during a 4-year period (jan. 91-dec. 94) of the charts of 26 patients (27 eyes) treated by pars plana vitrectomy for posteriorly dislocated crystalline lenses or lens fragments. One patient had a spontaneous lens luxation on both eyes and 3 patients presented with a posttraumatic dislocation of their lens. Twenty one eyes had retained intravitreal lens material after cataract surgery and 1 after perforating injury. Six eyes received an intraocular lens (IOL) at the end of the vitrectomy procedure; in 11 eyes an IOL had already been inserted at the time of primary cataract surgery. Ten eyes were left aphakic. Surgical details and visual outcome are discussed.

Non-arteritic anterior ischemic optic neuropathy and refraction.

A small cup-disk ratio has been reported as a risk factor in non-arteritic anterior ischemic optic neuropathy. Hyperopia is possibly related with a small cup-disk ratio. The purpose of the present study is to compare the refraction of 37 eyes with non-arteritic anterior ischemic optic neuropathy with a sex and age matched control group of 74 eyes. In our study, mild hyperopia was more frequently observed in the anterior ischemic optic neuropathy group than in the control group.

Ocular toxocariasis in a 36-year-old patient: a case report.

A 36-year-old female presented wit unilateral papillitis, followed by the development of a posterior pole granuloma. A positive ELISA-test for toxocara canis with a titer of 1/200 established the diagnosis. The patient was consecutively treated by pars plana vitrectomy and oral corticosteroids.