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Influence of alpha thalassaemia on the retinopathy of homozygous sickle cell disease.

Homozygous alpha+ thalassaemia (alpha-/alpha-) ameliorates some of the clinical manifestations of homozygous sickle cell (SS) disease but its effect on retinal complications remains unknown. This has been assessed by visual examination and fluorescein angiography in 39 subjects with SS disease and homozygous alpha+ thalassaemia and in 39 age/sex matched controls with SS disease but with a normal alpha globin genotype (alpha alpha/alpha alpha). The results indicate that homozygous alpha+ thalassaemia reduces the extent of peripheral retinal vessel closure but has no apparent effect on the frequency of proliferative sickle retinopathy.

Adolescent↗

Retinal 's' antigen disease in rats.

The form of experimental allergic uveoretinitis induced by sensitization with retinal 's' antigen in rats actually begins as a pars planitis and juxtapapillary choroiditis. Retinal inflammation develops at the middle limiting vascular layer of the retina and extends outward with focal destruction of photoreceptors and inward as a perivasculitis of small retinal vessels. Extensive choroiditis is a late development in severely diseased animals. Significant strain differences in susceptibility to disease were observed.

Animals↗

Clinical and immunologic characteristics of melanoma-associated retinopathy syndrome: eleven new cases and a review of 51 previously published cases.

OBJECTIVE: To evaluate the signs, symptoms, and immune responses of patients with melanoma-associated retinopathy (MAR) syndrome. MATERIALS AND METHODS: We reviewed the clinical and immunologic findings of 62 MAR syndrome patients. They include 25 patients from our institution (11 not previously reported) and 37 patients reported from other institutions. RESULTS: There were 33 men and seven women (no gender information is available for the remaining 22 cases). Age at onset of the visual disturbance averaged 57.5 years (range, 30-78). Visual acuity of 20/60 or better was initially present in 82%. Fundus examination was normal in 44%, optic disc pallor was present in 23%, and retinal vessel attenuation was present in 30%. Vitreous cells were present in 30%. The latency from melanoma diagnosis to recognition of MAR syndrome averaged 3.6 years (range, 2 months to 19 years). Seven patients sustained visual improvement with various treatment regimens, especially with intravenous immunoglobulin and cytoreductive surgery (metastasectomy). Indirect immunohistochemical staining of the bipolar layer was typical, but several other retinal elements were also reactive. Tissue from a metastatic melanoma excised from one of the patients expressed antigens that reacted with antiretinal antibodies. CONCLUSION: MAR syndrome demonstrates diverse clinical and immunologic features. Treatment, especially intravenous immunoglobulin and cytoreductive surgery (metastasectomy), improves vision in some cases.

Adult↗

Vascular retinopathy in migraine.

After years of episodic monocular visual loss, two migraineurs suffered sudden, persisting loss of vision from retinal vascular occlusion. One was a 34-year-old woman with systemic lupus erythematosus who showed abnormalities of the cilioretinal arterial and retinal venous circulations. The other was a 62-year-old man with hypertension and arteriosclerosis who had a central retinal vein occlusion. Persisting monocular visual loss is a rare consequence of migraine. Our cases suggest a role for venous lesions. Occlusion of retinal vessels in some migraineurs may result from the synergistic effect of another vascular disorder with the migraine.

Adolescent↗

The evolution of ocular toxoplasmosis in anti-interferon gamma treated mice.

PURPOSE: A clinico-histopathological cross correlation was made to study the mechanism of tissue damage in toxoplasmic retino-choroiditis during an experimental reactivation of chronic toxoplasmosis and to compare the influence of treatment by sulfadiazine on the retinal lesions. METHODS: Chronically infected Swiss-Webster mice were treated, six weeks after infection, with an avirulent strain of Toxoplasma gondii (Beverley strain) with polyclonal rabbit antibody directed against murine interferon gamma. RESULTS: Mice treated by anti-interferon gamma developed clinical lesions between day 5 and day 30 (lesions including single foci of retinochoroiditis, multifocal lesions or diffuse areas of retinal necrosis). These lesions did not arise from borders of pre-existing scars. The retina was photographed with an operating microscope fitted with a 90 diopter lens. Biological study showed a significant rise of parasitic loads in the eye and brain. Histological examination is in favour of free organism dissemination via retinal vessels; the lesions are restricted to the inner retina and ciliary body, the parasites migrated from extra-ocular cysts via the vasculature. No cysts were seen at the beginning of the study; they were found at the scar phase and appeared in mice treated with sulfadiazine. The clinical lesions were not caused by cysts but by coagulated necrosis in the retinal tissue. Parasite migration may have played a trigger role. CONCLUSIONS: The retinal damage was constituted either as a result of a toxic effect of the organisms or as a hypertensive reaction to the toxoplasma organism. The results of this study showed that the treatment with anti interferon gamma was sufficient to reactivate chronic infection.

Adrenal Cortex Hormones↗

[Etiology and final clinical cause for 1000 enucleations. (A clinico-pathologic study) (author's transl)].

From 1969-1974 1000 unselected enucleated globes have been examined histopathologically. 277 derive from the University Eye Hospital in Hamburg, 723 from various Eye Hospitals in northern and southern Germany. They originate from 589 men and 408 women, three times the sex was unknown. 86 globes had to be removed from children less than 15 years old. 6 groups of etiologies have been distinguished: trauma (308), histologically confirmed neoplastic disease (281), ocular manifestations of systemic diseases (diabetes mellitus, occlusions of central retinal vessels presumably following generalized vascular disease etc.: 128), "operative ocular disease" (164), primary inflammatory disease (71), miscellaneous (malformations, high myopia, pseudo-glioma and pseudo-melanoma: 48). The etiology "operative ocular disease" consists of 67 primary glaucomas (57 adults, 10 buphthalmus), 41 idiopathic cataracts (7 of these congenital) and 3 primary corneal dystrophies, as well as 53 cases of primary retinal detachment. Among the 281 neoplastic diseases, there are 238 primary intraocular malignant melanomas of the uvea, 18 retinoblastomas, 4 primary reticulumcellsarcomas of the retina, 2 choroidal nevi, 10 intraocular metastases and 9 orbital tumors. 16 enucleations among the 1000 enucleations have been performed for pseudo-gliomas (5 x Coats disease, 5 x persistent primary hyperplastic vitreous, 2 x retrolental fibroplasia, others 4 x). The manifestations of systemic disease are consisting of 68 central retinal vein-occlusions, 30 complications of diabetes mellitus and 10 central retinal artery occlusions as well as 20 other generalized diseases. A primary inflammatory disease led to enucleation 50 times due to an intraocular process, 5 times due to scleritis and 18 times as a consequence of keratitis (including 13 times herpes simplex). As the final clinical cause for enucleation the following categories have been elaborated: secondary glaucomas (416), clinical diagnosis of "tumor" (275), atrophy and phthisis bulbi (118), inflammation (112), acute trauma to 4 weeks after the accident (72), others (7). In conclusion the central role of rubeosis iridis leading to secondary angle closure glaucoma is emphasized. This process presents a challenge to ophthalmologic research. Finally the significance of early surgery for primary angle closure glaucomas and for complete restoration of the anterior chamber after trauma and any intraocular procedure is stressed.

Cataract Extraction↗

Color doppler imaging of ocular hemodynamic changes in Behçet's disease.

PURPOSE: A prospective evaluation of the ocular blood flow velocity in patients with BehCet's disease was carried out to determine its changes. METHODS: Subjects were divided into three groups: those with ocular involvement in BehCet's disease (group I), those without ocular involvement in BehCet's disease (group II), and a control group (group III). Twenty-seven eyes in group I and 28 eyes each in groups II and III were investigated. The blood flow in the central retinal artery (CRA), ophthalmic artery (OA), nasal posterior ciliary artery (NPCA), and the temporal posterior ciliary artery (TPCA) was measured using color Doppler ultrasonography (CDU) to determine the peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI). The mean blood flow velocity of the central retinal vein (CRV) was also measured. These results were then compared among the three groups of subjects. RESULTS: The PSV values of CRA in groups I and II were found to be significantly lower than those in the control group ( P < 0.001, P = 0.018, respectively). The PSV values of CRA in group I were found to be significantly lower than those in group II ( P< 0.001). The EDV values of CRA in groups I and II were found to be significantly lower than those in the control group ( P< 0.001, P = 0.034, respectively). The EDV values of CRA in group I were significantly lower than those in group II ( P = 0.041). The PSV values of OA in group I were significantly lower than those in the control group ( P = 0.002). The EDV values of OA in group I were significantly lower than those values in group II or the control group ( P = 0.001 and P = 0.037, respectively). The PSV values of NPCA in group I were significantly lower than those in the control group ( P = 0.007). The PSV values of TPCA in groups I and II were significantly lower than those in the control group ( P< 0.001, P < 0.001, respectively). The EDV values of TPCA in group I were significantly lower than those values in group II or the control group ( P = 0.014 and P = 0.003, respectively). There were no significant differences in the mean blood flow values of the CRV among all three groups ( P > 0.05). CONCLUSIONS: There are significant reductions in the blood flow values of the orbital arteries in patients with BehCet's disease, and they are more evident in those with ocular involvement. This might be the result of occlusive vasculitis, which is frequently seen in the retinal vessels of patients with BehCet's disease.

Adolescent↗

[Occlusion of the central retinal vein in hemodialyzed patients].

The authors describe the acute development of an occlusion of the main retinal vein in six patients enlisted in a chronic dialyzation programme. It is a very serious ophthalmological complication which caused substantial diminution of visual acuity, and where haemorrhagic glaucoma developed (4 patients), loss of the eye. In investigations of these patients enlisted in chronic dialyzation programmes pathological findings on the ocular fundus are decisive. Patients with hypertonic neuroretinopathy on the ocular fundus run the greatest risk of occlusion of retinal vessels, in particular in the first year after enlistment in the programme. Impaired blood clotting in these patients certainly also plays a part in the development of the occlusion.

Adult↗

A comparison of manual and automated methods of measuring conjunctival vessel widths from photographic and digital images.

We investigated the application of a fully automated computer algorithm for identifying vessels of the conjunctiva from their scleral surround, and compared measures of vessel width with established methods. Vessel widths at 101 locations (ranging from 20 to 140 microm), from 12 patients, were measured from film and digital images, using a variety of methods, and compared. Widths were measured manually, by semi-automated methods using grey level (densitometric) profiles taken from digital images, and by automated techniques set at different operating levels. Good intra-session repeatibility was obtained using the automated method with an operating sigma value of 3 pixels (16 microm) (mean difference 0.5 microm, 95% CI -8.5 to 9.4 microm) and manual calliper measurements from digitally created photographic slides (mean difference 0.4 microm, -9.3 to 10.1 microm). For comparison with other measures of width, the latter was used as the gold standard. Widths measured from film were slightly larger than those measured directly from digital images, although this effect was small (5 microm) for most vessels. Overall widths measured using the automated method, with a sigma value of 3 pixels, agreed best with the gold standard (inter-method repeatibility; mean difference 1.4 microm, -32.5 to 35.2 microm) although the automated method overestimated small widths (<40 microm) and underestimated larger vessel widths (>40 microm). Automated detection of vessels of the conjunctiva from digital images avoids manual and operator involved measures which are time consuming, and which preclude large patient studies. The resulting data may help in monitoring the vascular response of the conjunctiva to surgical or pharmacological intervention, and in describing vascular changes in response to ocular or systemic disease. The application of this algorithm to the study of retinal vessels is yet to be realised.

Algorithms↗

[Clinically isolated Morning glory syndrome].

The Morning glory syndrome is an uncommon congenital optic disk anomaly. It is characterized by a funnel-shaped and enlarged dysplasic optic disk with white tissue, and retinal vessels arising from the periphery of the disk and running an abnormally straight course over the peripapillary retina. We report here the case of a 7-year-old girl with a delayed diagnosis of Morning glory syndrome discovered at a regular examination that showed amblyopia. The optic disk anomaly was isolated. The search for other associated morphological and/or functional abnormalities is mandatory (retinal and/or cerebral malformation, frontonasal dysplasia, endocrine irregularities, neurofibromatosis type 2). Periodic ophthalmological examinations are recommended due to the frequency of retinal detachment.

Amblyopia↗

[Automated measurement of retinal vascular diameter].

We describe a new unit of the Jena retinal camera for automatic measurement of retinal vessel diameter. The brightness profile perpendicular to the vessel is registered by CCD line sensor and the signal is transmitted to the computer. An adaptive computer program recognizes the edges of vessels and estimates the vessel diameters automatically. Applying several measurements per vessel, the intraindividual standard deviation may be smaller than 3%. By using the same objective measuring edge criterion, the measuring results are comparable between different observers and methods. Error sources are discussed. Measured vessel reactions to oxygen breathing and reduced perfusion pressure are presented to demonstrate the efficiency of this new method.

Adult↗

Color Doppler imaging of ocular hemodynamic changes in Behçet disease and uveitis patients with different etiologies.

PURPOSE: To investigate blood flow velocity changes and resistivity index values of orbital vessels in Behçet disease with or without ocular involvement, in uveitis patients with different etiologies, and in healthy volunteers. METHODS: Subjects were divided into four groups: those with ocular involvement in Behçet disease (group I), those without ocular involvement in Behçet disease (group II), uveitis patients with different etiologies (group III), and a control group (group IV). Twenty-seven eyes in group I, 14 eyes in group II, 25 eyes in group III, and 27 eyes in group IV were investigated. The blood flow in the central retinal artery (CRA), ophthalmic artery (OA), nasal posterior ciliary artery (NPCA), and the temporal posterior ciliary artery (TPCA) was measured using color Doppler ultrasonography (CDU) to determine the peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI). RESULTS: The PSV and EDV value of CRA in groups I, II, and III were found to be significantly lower than those in the control group (p < 0.05 for each). The PSV and EDV values of TPCA and NPCA in groups I, II, and III were significantly lower than those in the control group (p < 0.05 for each). Resistivity indexes of all arteries were higher in groups I, II, and III than the control group. The PSV and EDV in CRA, TPCA, and NPCA in Behçet disease patients with ocular involvement were significantly lower than all other groups (p < 0.05). CONCLUSIONS: There are significant reductions in the blood flow values of the orbital arteries in patients with Behçet disease and uveitis patients with different etiologies when compared with healthy volunteers. The decrease in blood flow values in Behçet disease is more evident in patients with ocular involvement than the patients without ocular involvement. This might be the result of occlusive vasculitis, which is frequently seen in the retinal vessels of patients with Behçet disease.

Adolescent↗

The intensity of the light reflex on retinal arteries and veins.

The intensity profiles of the central light streak on various sized retinal vessels were measured by a computerized high quality scanning microphotometer. From the fundus photographs in 40 young men 240 arteries and 240 veins were analysed, and light streaks were found on 171 arterial and 170 venous sites. Differences in reflected intensities between arteries and veins and between small and large vessels were studied. In the whole range of vessels measured (50-200 microns) significantly higher intensities were found on arteries compared to veins (P less than 0.01). Large vessels (100-200 microns) reflected the light more intensely than small vessels (50-99 microns) (P less than 0.001). Variations in haemodynamics of flow and in physical properties of the streaming erythrocytes might account for the reflectivity differences between arteries and veins.

Adult↗

Effect of an internal carotid stenosis on orbital blood velocity.

PURPOSE: To examine how an internal carotid artery (ICA) stenosis influences the orbital blood velocity and to determine which velocity parameters are most useful. MATERIAL AND METHODS: The study group comprised 94 randomly selected patients examined with orbital US; most of the patients had a carotid artery stenosis. There were 58 men and 36 women, ranging in age from 22 to 88 years with a mean age of 63.1 years. The ICA stenosis grade was determined with carotid US. Peak systolic (Vp) and end-diastolic blood velocities, systolic acceleration, mean velocity, pulsatile index (PI) and resistance index (RI) were measured within the central retinal artery (CRA) and the ophthalmic artery (OA), and peak velocity was measured within the central retinal vein (CRV). The area under the ROC curve was used to compare the outcome of diagnostic tests. RESULTS: Only a severe (> or =80%) ICA stenosis decreased orbital blood velocity significantly, while milder stenoses did not cause significant flow decrease or side differences. According to ROC curve analysis, the threshold values giving the highest accuracy in detecting a > or =80% ICA stenosis were Vp < or =0.08 cm/s for the CRA and Vp < or =0.14 cm/s for the OA. The sensitivities for detecting a > or =80% ICA stenosis were 45% for Vp CRA and 60% for Vp OA. Systolic acceleration also decreased in severe stenoses, but RI, PI and velocity in the CRV did not correlate with ICA pathology. Reversal of OA flow was seen in 92% of ICA occlusion and in 47% of severe ICA stenosis. CONCLUSION: Orbital Doppler combined with carotid Doppler can be helpful in the diagnosis of the ocular ischaemic syndrome and in the evaluation of whether the symptoms are related to occlusion of the ophthalmic or central retinal vessels or are a consequence of carotid artery stenosis.

Adult↗

Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, II: Structural measures.

PURPOSE: To determine, using anatomic measurements, whether daily oral dosing with memantine is both safe and effective to reduce the injury associated with experimental glaucoma in primates. METHODS: Argon laser treatment of the anterior chamber angle was used to induce chronic ocular hypertension (COHT) in the right eyes of 18 macaque monkeys. Nine animals were daily orally dosed with 4 mg/kg memantine while the other nine animals received vehicle only. Measurements of intraocular pressure (IOP) from both eyes of all animals were made at regular intervals. Appearance of the optic nerve head, retinal vessels, and surrounding retina was documented with stereo fundus photographs obtained at multiple time points throughout the study. Measurements of optic nerve head topography were obtained from confocal laser scans made from animals with the highest IOPs at approximately 3, 5, and 10 months after elevation of IOP. At approximately 16 months after IOP elevation, animals were killed and histologic counts of cells in the retinal ganglion cell (RGC) layer were made. RESULTS: Histologic measurements showed that, for animals with moderate elevation of IOP, memantine treatment was associated with an enhanced survival of RGCs in the inferior retina. Measurements of optic nerve head topography showed less IOP-induced change in memantine-treated animals. This effect was seen in measurements of both the cup and the neuroretinal rim. A comparison of these same histologic and morphologic measurements in normotensive eyes from the two treatment groups showed that memantine treatment was not associated with any significant effects on these eyes. CONCLUSIONS: Histologic measurements of RGC survival as well as tomographic measurements of nerve head topography show that systemic treatment with memantine, a compound which does not lower intraocular pressure, is both safe and effective to reduce changes associated with experimental glaucoma.

Administration, Oral↗

[21st century management of glaucoma].

According to a recent epidemiological study done in Japan, 2 or 3 million Japanese people are thought to be suffering from glaucoma, and 70-80% of them have not been examined or diagnosed by ophthalmologists. Therefore, the problem is how to find these untreated and undiagnosed people. At present, treatment of glaucoma continues to be directed at lowering intraocular pressure to prevent progression of glaucomatous optic neuropathy. However, theoretically, there are three stages in the prevention of progression of glaucoma. In the first stage, diagnosis of glaucoma can be done by genetic examination, before occurrence of glaucoma. The MYOCILIN/trabecular meshwork-inducible glucocorticoid response gene and the optineurin gene were identified as the genes that cause open angle glaucoma. Although some Japanese patients have sequence changes in the myocilin gene, there are no apparent specific mutations in Japanese glaucoma patients, in the MYOCILIN/TIGR and optineurin genes. Secondary glaucoma such as steroid glaucoma, induced by allergic diseases, and neovascular glaucoma, induced by retinal circulatory insufficiency, are preventable by improving the causal diseases, diabetes and hypertension. The education of doctors and laymen is important to reduce the occurrence of diabetes, and hypertension to prevent diabetic retinopathy, and retinal vessel occlusion. The second stage in preventing progression of glaucoma is to find the disease as early as possible. In Japan, a physical examination system is in place for everybody over 40 years old, in companies and local districts. Therefore, ocular examination, specially non-mydriatic fundus photographs should be taken in these examinations, and the film should be evaluated by an ophthalmologist, to search for retinal and optic disc abnormalities. Primary open angle glaucoma can be detected through this system in early stages. In primary angle closure glaucoma, instruments for estimating anterior chamber rapidly and accurately are necessary for the diagnosis. There is a special machine which can be handled easily, safely, and economically for detecting angle closure glaucoma, has been developed by Yamanashi University. This machine might help to reduce the number of angle closure glaucoma patients in the world. In the near future, a glaucoma network system should be put in place all over Japan. This organization consists of central headquarter and local central office. Most hospitals and private offices will belong to a local central office, and several glaucoma specialists will work in central and local offices. All glaucoma patients will be registered in local glaucoma office. The information on glaucoma patients will be communicated in the system the through light fiber cables or a satellite system. The patients can ask about their own disease through this glaucoma center system. In the third stage of glaucoma prevention, progression of glaucomatous optic neuropathy is retarded by conventional IOP lowering treatment or neuroprotective drugs. This stage compromises rehabilitation of visual function, implant of artificial visual systems, and regeneration of retinal ganglion cells(RGC). The disturbances of axonal flow in guinea pig optic nerve fibers was demonstrated electromicroscopically by quick-freeze, deep-etching method and, the decrease in numbers of motor proteins like "Kinesin" "Dynein" and "MAP-1" was shown in guinea pig eyes with elevated intraocular pressure by immunohistochemistry. Retinal glanglion cells have been isolated and new findings have been reported using this RGC culture system. Therefore, new neuroprotective drugs will be developed through this culture system.

Animals↗

Idiopathic preretinal fibrosis with concurrent cystoid macular edema.

Idiopathic preretinal fibrosis is a common disorder which typically affects elderly individuals. The epiretinal membranes are of glial origin in the retina where they migrate through breaks in the internal limiting membrane to form fibroglial sheets on the surface of the retina. Although visual symptomatology is rare, the epiretinal membranes may, in some instances, grow rapidly and contract causing tractional changes to occur involving the underlying retina and retinal vessels. This paper presents a case of preretinal fibrosis with accompanying cystoid macular edema and consequent dramatically reduced vision. The diagnosis, pathophysiology and management of preretinal fibrosis are discussed.

Aged↗

Measurement of fluorescein angiograms of the optic disc and retina using computerized image analysis.

Computerized image analysis was used to quantify objectively fluorescein angiograms of the optic disc, peripapillary choroid, and retina. Techniques were developed to measure fluorescein filling rates of the optic disc and the retinal vessels and the area of fluorescein filling defects within the optic disc. Two subjects, one with glaucoma and the other with ocular hypertension, showed increases of areas of fluorescein filling defects of the optic disc on follow-up and are presented here as examples of the application of these techniques. This methodology can be applied to the longitudinal follow-up of individual patients with glaucoma and retinal diseases, as well as to cross-sectional studies of patient populations.

Adolescent↗