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PubMed1977

Optic disc edema in raised intracranial pressure. II. Early detection with fluorescein fundus angiography and stereoscopic color photography.

Optic disc edema (ODE) due to chronic intracranial hypertension was produced experimentally in rhesus monkeys. Serial studies of fundus changes at frequent intervals, by routine ophthalmoscopy, steroscopic color photography, and fluorescein angiography, revealed that swelling of the optic disc was the first sign of ODE. Other early signs were striation of nerve fibers on the optic disc margins and peripapillary retina, blurring of the disc margins, hyperemia of the disc and capillary dilation, hemorrhages, and other retinal vascular changes; these usually appeared in that sequence. The classically described signs of early ODE were almost always absent. A normal fluorescein fundus angiogram during the incipient stage did not rule out ODE. Stereoscopic color fundus photography was the most sensitive means of detecting early ODE. Fluorescein angiography did not show changes till edema was of a mild to moderate degree; routine ophthalmoscopy was the least reliable method.

Aneurysm↗

PubMed1979

Autosomal dominant dystrophy of the retinal pigment epithelium.

This study describes a salt-and-pepper fundus appearance in nine relatives in three generations of a single white kindred. Two of these patients also had subretinal patterned pigment figures by ophthalmoscopy. In another, fluorescein angiography showed a reticular pattern that was not apparent by ophthalmoscopy. This dystrophy was functionally benign, although the electro-oculogram ratio was abnormal in affected patients. This pigmentary dystrophy and fundus pulverulentus, reticular dystrophy of Benedikt and Werner, and pattern dystrophy of Marmor and Byers are indistinguishable. When patterned pigment figures are absent, this autosomal-dominant pigmentary dystrophy of the retinal pigment epithelium can be confused with other disorders such as congenital rubella retinopathy and drug toxicity.

Adolescent↗

PubMed1985

Clearance of triamcinolone from vitreous.

The clearance of intravitreally injected triamcinolone acetonide was monitored by both indirect ophthalmoscopy and high-performance liquid chromatography (HPLC) and found to be more rapid than previously reported by others. Twenty-four rabbits were intravitreally injected in each eye with 0.4 mg of triamcinolone acetonide. Three rabbits each were sacrificed at intervals ranging from one hour to 46 days. The vitreous was then harvested and processed for HPLC analysis. Triamcinolone and the internal standard prednisolone were identified and quantitated by the use of HPLC, which was found to be both sensitive and specific for the steroids. The half-life as determined by HPLC was 1.6 days, the level at 13 days postinjection was 66 +/- 19 micrograms, and no drug was detectable by HPLC analysis at 21 days in five of six eyes. The intravitreal masses thought to be triamcinolone were clinically observable to an average of 23.3 days. The chromatographically determined clearance rate did not correlate well with clinical impressions based on indirect ophthalmoscopy.

Animals↗

PubMed1991

Retinal toxicity of human tissue plasminogen activator in vitrectomized rabbit eyes.

The retinal toxicity of human tissue plasminogen activator in normal rabbit eyes has recently been reported. We now report the retinal toxicity of tissue plasminogen activator in three groups of vitrectomized rabbit eyes. Group 1 underwent gas compression of the vitreous followed by tissue plasminogen activator injection in doses of 25, 50, and 100 micrograms (all doses were administered in 100 microL of fluid). Group 2 underwent lensectomy and vitrectomy followed by tissue plasminogen activator injection of 100 micrograms. Group 3 underwent lensectomy, vitrectomy, and complete fluid/gas exchange prior to injections of 12.5 and 25 micrograms of tissue plasminogen activator. Control eyes received 100 microL of balanced salt solution. In group 1, no retinal toxic reactions were observed after administration of 25 or 50 micrograms of tissue plasminogen activator, but all eyes receiving 100 micrograms demonstrated retinal damage on ophthalmoscopy, electroretinography, and light microscopy. In group 2, no retinal toxic reactions were seen after administration of 100 micrograms of tissue plasminogen activator. In group 3, two of 11 eyes receiving 25 micrograms of tissue plasminogen activator demonstrated toxic retinal changes by ophthalmoscopy, electroretinography, and light microscopy. These results suggest that gas compression of the vitreous does not significantly alter the toxic changes seen caused by tissue plasminogen activator. While lensectomy and vitrectomy appears to widen the therapeutic window for tissue plasminogen activator, the margin of safety is reduced with the addition of a large gas bubble.

Animals↗

PubMed1994

Ocular findings associated with a Cys39Arg mutation in the Norrie disease gene.

OBJECTIVE: To diagnose the carriers and noncarriers in a family affected with Norrie disease based on molecular analysis. DESIGN: Family members from three generations, including one affected patient, two obligate carriers, one carrier identified with linkage analysis, one noncarrier identified with linkage analysis, and one female family member with indeterminate carrier status, were examined clinically and electrophysiologically. Linkage analysis had previously failed to determine the carrier status of one female family member in the third generation. Blood samples were screened for mutations in the Norrie disease gene with single-strand conformation polymorphism analysis. The mutation was characterized by dideoxy-termination sequencing. RESULTS: Ophthalmoscopy and electroretinographic examination failed to detect the carrier state. The affected individuals and carriers in this family were found to have a transition from thymidine to cytosine in the first nucleotide of codon 39 of the Norrie disease gene, causing a cysteine-to-arginine mutation. Single-strand conformation polymorphism analysis identified a patient of indeterminate status (by linkage) to be a noncarrier of Norrie disease. CONCLUSION: Ophthalmoscopy and electroretinography could not identify carriers of this Norrie disease mutation. Single-strand conformation polymorphism analysis was more sensitive and specific than linkage analysis in identifying carriers in this family.

Adult↗

PubMed1992

Role of congenital hypertrophy of the retinal pigment epithelium in the predictive diagnosis of familial adenomatous polyposis.

A study was carried out to evaluate congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a disease marker in a defined population with familial adenomatous polyposis (FAP). Indirect ophthalmoscopy was performed on 75 individuals from 25 known families with FAP, of whom 32 were known to be affected and 43 were at a 50 per cent prior risk of developing the disease. A further ten individuals from five families with hereditary non-polyposis colorectal cancer (HNPCC) were also tested. CHRPE was seen in 28 of the 32 affected individuals, 27 of whom met the criteria for a positive examination. Three individuals at risk of FAP also had positive examinations. Five individuals from the families with HNPCC also had CHRPE, although none met the criteria for a positive examination. Of four types of CHRPE analysed, one (small pigmented dots) was found to be more frequent in older family members (P = 0.012), suggesting that this type of lesion may proliferate with age. Compliance with ophthalmic screening was 97 per cent in families with FAP. Using a combined set of diagnostic criteria, CHRPE identified affected individuals with a specificity of at least 94 per cent and a sensitivity of 84 per cent. Results argue for a combined screening programme for FAP of DNA analysis, indirect ophthalmoscopy and bowel examination.

Adenomatous Polyposis Coli↗

PubMed1999

Evaluation of the human choroidal melanoma rabbit model for studying microcirculation patterns with confocal ICG and histology.

The aim of this study was to develop consistently focal elevated choroidal masses of human choroidal melanoma in immunosuppressed rabbits and to correlate the visualization of prognostically significant microcirculation patterns from confocal indocyanine green angiography with histologic microcirculation patterns. A human choroidal melanoma cell line (OCM1) was implanted in the choroid of 40 rabbit eyes using three different techniques: transscleral choroidal injection of a cell suspension, injection of a cell suspension in a surgically induced cyclodialysis cleft, and implantation of solid tumor fragments in a surgically induced cyclodialysis cleft. The rabbits were immunosuppressed with daily injections of Cyclosporin A to prevent host versus graft reaction. The eyes were studied weekly with indirect ophthalmoscopy and fundus photography to monitor tumor growth and indocyanine green angiography using a confocal scanning laser ophthalmoscope to identify microcirculation patterns in vivo and correlate these findings with the histologic demonstration of tumor microcirculation patterns. A tumor mass was identified by indirect ophthalmoscopy in 16 of the 40 implanted rabbit eyes (40%). Each of these tumors was confirmed histologically to represent a focal elevated choroidal mass. All 16 elevated choroidal masses grow in eyes in which solid tumor fragments were implanted. In total, a melanoma was identified histologically in 28 of the implanted 40 eyes (70%). In addition to the 16 eyes where the melanoma appeared as a focal elevated choroidal mass, 4 eyes contained a focal elevated mass in the sclera and 8 eyes contained a flat choroidal tumor. Histologically, microcirculation patterns were identified only in the 16 eyes with focal elevated choroidal masses. Confocal indocyanine green angiography imaged microcirculation patterns in 13 of these 16 eyes (81%). The surgical implantation of small solid fragments of human choroidal melanoma in immunosuppressed rabbit eyes provides the best method to consistently obtain focal elevated choroidal masses. These focal elevated choroidal masses resemble booth the localization and the growth pattern of choroidal melanomas in humans. In addition, they also contain microcirculation patterns similar to those seen in humans that are detectable with confocal indocyanine green angiography. The use of indocyanine green angiography with this animal model may be especially useful in designing and evaluating anti-microcirculation treatments directed at uveal melanoma.

Angiography↗

PubMed1983

Fluorescein angiography of the choroid in health and disease.

Fluorescein angiography of the normal fundus reveals the segmental nature of the choroidal vascular bed. Despite the presence of anatomically demonstrable anastomoses, a segmental distribution is present in vivo up to the choriocapillaris level. Choroidal vascular diseases manifest by localized of diffuse delayed or incomplete filling of the choroid and by the involvement of the overlying retinal pigment epithelium. In the acute phase of choroidal arterial occlusive disease, ophthalmoscopy reveals localized or diffuse edema. Fluorescein angiography of such cases initially shows a delayed perfusion of the involved area followed later on by fluorescein leakage. This late diffusion of the dye is probably related to alterations of the retinal pigment epithelial barrier. The extent of the lesion after resolution of the edema mainly depends on the site and the extent of the occlusion, on the development of collaterals and possibly on the involvement of the choroidal venous circulation. Ophthalmoscopy and fluorescein angiography will reveal localized or diffuse pigmentary changes, sometimes of quite characteristic aspect. This may be associated with local destruction of the choriocapillaris, although normalization of choroidal blood flow may also be observed. Chronic choroidal vascular insufficiency is a possible cause for choroidal sclerosis. Chronic choroidal ischemia is also a possible explanation for peripheral pigmentary changes seen in the elderly.

Adult↗

PubMed1991

Retinal blood flow in diabetic children and adolescents.

A total of 209 diabetic children and adolescents aged 6-17 years (mean, 12.6 +/- 2.3 years) were examined by ophthalmoscopy, video fluorescein angiography and hemoglobin (HbA1c) test. Microaneurysms were found in 26% of the children (ophthalmoscopy, 11%; angiography, 23%). The prevalence of retinopathy was 16% in patients aged 6-10 years, 27% in those aged 11-13 years and 36% in those aged 14-17 years. Only five diabetics aged 11-17 years showed lesions other than microaneurysms (hard exudates, intraretinal hemorrhages or retinal capillar leakage). Retinal blood flow was quantified using video fluorescein angiography. The arm-retina time (ART) and the arteriovenous passage time (AVP) as parameters of the retinal microcirculation were obtained using an image analysing system. The mean value for ART was 9.7 +/- 2.5 s and that for AVP was 1.43 +/- 0.52 s. AVP was significantly shorter in diabetic children and adolescents with good glycemic control (HbA1c, less than 7%; AVP, 1.35 +/- 0.44 s) than in those with bad glycemic control (HbA1c, greater than or equal to 9%; AVP, 1.65 +/- 0.51 s).

Adolescent↗

PubMed1989

Fundus changes associated with Behçet's disease.

Between 1973 and 1987 we recorded 300 cases of Behçet's disease with fundus changes. Our routine preview of each case included examination with the Goldman three-mirror contact lens, ophthalmoscopy, referral for laboratory tests, color fundus photography and, most importantly, fluorescein angiography. The ophthalmological findings led to the proper diagnosis in 254 (85%) of our cases. Fluorescein angiography revealed incipient fundus changes in 38 eyes of 19 medically diagnosed patients with no visual complaints and normal fundi on ophthalmoscopy. Eighty-six percent of our cases had or developed diverse fundus changes bilaterally. The fundus changes we encountered most frequently were hyperemia of the optic disc, macula edema, retinal edema, vascular sheathing, retinal exudate, and retinal hemorrhage. With the exception of eyes with very poor prognoses, only 184 of the 403 eyes that were followed up for 3-120 months (median 12) experienced new insults in the posterior segment; 40 of these became totally blind while 59 maintained their visual status. Early diagnosis is necessary for proper treatment patients with Behçet's disease. Fluorescein angiography is required for early diagnosis and for monitoring the posterior segment involvement closely. This is the most characteristic and often the most serious consequence of Behçet's disease; it may also the first indicator of the disease.

Adolescent↗

PubMed1986

Prevalence and development of retinopathy in children and adolescents with type 1 (insulin-dependent) diabetes mellitus. A longitudinal study.

In 231 subjects with Type 1 diabetes mellitus aged 17.6 +/- 4.0 years, with a diabetes duration of 8.5 +/- 4.9 years at the end of the study, the prevalence and the development of retinopathy during a period of 5 years were studied. All patients were examined between one and six times both by ophthalmoscopy and fluorescein angiography. A total of 626 fluorescein angiographies were evaluated. By the end of the study, 109 out of 231 patients (47%) had developed retinal changes, half of which were classified as minimal (less than 5 microaneurysms). Thirty-eight patients (35% of those affected) had background (n = 28) or proliferative (n = 10) retinopathy. In subjects less than 15 years of age and diabetic for less than 5 years, retinal lesions were rare. With increasing age and duration of diabetes, both the prevalence and severity of retinal changes increased markedly. Life-table analysis was used to calculate the median individual risk for the development of early retinal changes, which was 9.1 years of diabetes duration. This risk differed in sub-groups with different ages at onset of diabetes, i.e. 12.1, 8.9 and 6.6 years (p less than 0.0001), with diabetes starting below 4, between 5 and 9, and after 10 years of age respectively. After 18 years of diabetes, every patient demonstrated at least incipient structural changes. Fluorescein angiography allowed the detection of retinopathy, on average, four years earlier than with ophthalmoscopy. The median interval between the 'onset' of retinopathy, as indicated by a few microaneurysms, and background retinopathy was 5 years.

Actuarial Analysis↗

PubMed2004

Retinopathy of prematurity--risk factors.

OBJECTIVE: Improved survival of low birth weight, premature babies have increased the incidence of retinopathy of prematurity. This hospital-based, prospective, study was undertaken to determine its incidence and risk factors in our neonatal unit. METHODS: Neonates with gestational age < or = 35 weeks and/or birth weight < or = 1500 gm born over a one-year period were examined by indirect ophthalmoscopy between 2 to 4 weeks after birth, and followed up till retinal vascularisation was complete. Maternal and neonatal risk factors were noted and data analyzed by statistical package SPSS-10.0. RESULTS: Sixty babies were thus examined. The incidence of retinopathy was 21.7% in the cohort, 33.3% in babies < or = 32 weeks gestation and 36.4% in babies weighing < or = 1250 gm. Oxygen (p=0.01), sepsis (p=0.04) and apnoea (p=0.02) were independent risk factors. Retinopathy was significantly more severe in babies with hyaline membrane disease (p=0.02) and lower birth weight (p=0.02). Severe disease was never seen before 6.5 weeks of age. CONCLUSION: Indirect ophthalmoscopy should be performed at 4 weeks of post natal age in all preterm babies with birth weight < or = 1500 gm, and intensified in the presence of risk factors like oxygen administration, apnoea and septicemia.

Apnea↗

PubMed2004

An experimental rabbit model of rhegmatogenous retinal detachment.

An experimental model of rhegmatogenous retinal detachment (RRD) in rabbits was established to simulate the pathophysiologic condition of human RRD. 24 rabbits were randomly divided into 3 groups and underwent vitrectomy with a vitrector and/or retinotomy with a Charles flute needle, with 12 in group I (vitrectomy and retinotomy), 7 in group I (retinotomy) and 5 in group III (vitrectomy). All animals underwent follow-up examinations with direct and indirect ophthalmoscopy and fundus photography 12 h and day 1, 3, 5, 7, 10, 14, 21, and 28 after the procedure(s). Retinal changes were recorded. As a result, 10 RRDs were successfully established in group I. Direct and indirect ophthalmoscopy and fundus photography demonstrated typical features of RRD. No RRD developed in group II and III. It was concluded that the experimental rhegmatogenous retinal detachment produced in a rabbit model after vitrectomy with retinotomy in this study was a convenient and reliable one. This RRD model mimicked the typical pathophysiological changes in humans.

Animals↗

PubMed2005

Age-related macular disease: how to assess the retina using scanning laser techniques?

Age-related macular disease (AMD) is the leading cause of legal blindness among the elderly in Western nations. The magnitude of the problem will undoubtedly grow, as age is a significant risk factor and the number of people aged 65 and over is projected to increase. The most frequent cause of severe visual loss associated with AMD is irreversible degeneration of the overlying neurosensory retina, caused by the growth of choroidal neovascularization or, alternatively, the development of geographic atrophy of the retinal pigment epithelium. Today, we are able to image the human retina in vivo. Recently developed imaging techniques provide better assessment of retinal pathology than conventional ophthalmoscopy alone. This overview presents the most recent devices available for retinal imaging, which mainly exploit laser technology such as scanning laser ophthalmoscopy. Its basic principles, as well as its characteristics for imaging and functional assessment of the retina, are described. Lastly, potential benefits for clinical routine, rehabilitation strategies in AMD, and future research aspects are discussed.

Aged↗

PubMed2000

Inhibition of diclofenac formulated in hyaluronan on angiogenesis in vitro and its intraocular tolerance in the rabbit eye.

PURPOSE: To investigate the effect of diclofenac, a potent nonsteroidal anti-inflammatory drug, formulated in hyaluronan (diclofenac/HA) on angiogenesis in vitro and its intraocular toxicity in vivo. METHODS: The effect of diclofenac/HA on angiogenesis was determined by choriocapillary endothelial cells on Matrigel stimulated by vascular endothelial growth factor (VEGF). The tube areas were quantified by image digital analysis. For toxicity study, diclofenac/HA was injected intravitreally with a dose range from 100 to 1080 microg in 26 rabbits following gas compression vitrectomy. Potential toxicity was assessed by indirect ophthalmoscopy and by histological studies (light and electron microscopy). Retinal function was monitored by electroretinography (ERG) in six rabbits that received 400 microg of diclofenac/HA. RESULTS: Diclofenac/HA, 180, 90 microg/ml, inhibited tube formation to 24% and 55% of the standard group (Media Ham's F12 plus 5% fetal calf serum and 50 ng/ml VEGF) respectively (P<0.01). Intravitreal injection of 540 microg or higher doses of diclofenac/HA resulted in ocular toxicity in the rabbit, demonstrated as cataract, vitreous haze and retinal damage observed by indirect ophthalmoscopy and light- and electron-microscopic examinations. No toxicity was observed in the eyes that received 400 microg or less diclofenac/HA, which was further supported by the normal ERG examined at 4 and 25 days post injection. CONCLUSIONS: Diclofenac/HA inhibits tube formation in vitro and is non-toxic to the rabbit retina at concentrations that are inhibitory to tube formation. Our results suggest diclofenac/HA may be an effective candidate to inhibit ocular neovascularisation related to granulomatous reaction in the eye.

Animals↗

PubMed1980

Pupillary dilatation with single eyedrop mydriatic combinations.

We studied the mydiatic effect of three solutions containing a combination of two mydriatic drugs in 80 adult patients. The solutions tested were cyclopentolate HCl 0.5% with phenylephrine 2.5%, tropicamide 0.5% with phenylephrine 2.5%, and tropicamide 1.0% with phenylephrine 2.5%. We evaluated the effect of prior instillation of proparacaine 0.5% eyedrops. All three mydriatic combination solutions evaluated produced pupillary dilatation of about 7 mm within 60 minutes. Additional pupillary dilatation of 1 mm occurred when proparacaine was instilled before the mydriatic combination eyedrop. Mydriasis was resistant to bright light during indirect ophthalmoscopy in all patients. Pupils of younger patients dilated better than those of older patients, but sex and iris color were factors in the amount of pupillary dilatation obtained. Wide and sustained pupillary dilatation can be obtained for satisfactory indirect ophthalmoscopy by the instillation of one drop of proparacaine solution followed by a single drop of any of the three mydriatic combination solutions evaluated. By eliminating the need for multiple instillations of drugs, the use of a single eyedrop mydriatic combination is convenient in terms of time saved and also lessens the change of systemic drug toxicity.

Adolescent↗

PubMed1990

Fluorophotometric assessment of blood-retinal barrier function after white light exposure in the rabbit eye.

Fluorophotometry was performed in 14 rabbits after exposure of one eye to white light with an energy insufficient to cause visible phototoxic retinal damage as determined by ophthalmoscopy and fundus photography. Fluorescence measurements in the vitreous were performed before and 1 hr after i.v. injection of fluorescein. Ratios between the fluorescein concentrations in the exposed and in the non-exposed fellow eye were calculated after correction for the autofluorescence. The average ratio directly after light exposure had significantly increased (P = 0.005) as compared to pre-exposure values and was maximal one day after exposure (P less than 0.005). Four days after exposure the ratios had returned to pre-exposure values (P greater than 0.05). A significant linear correlation between age and the ratios directly after exposure was found (r = -0.67; P less than 0.01). Signs of phototoxic retinal damage were not found on ophthalmoscopy and fundus photography, nor on light and electron microscopic examination of the retinal pigment epithelium, neuro-retina or retinal capillaries 1 and 4 days after light exposure. A fluorophotometric assessment of the blood-retinal barrier (BRB) function after white light exposure appeared to be a more sensitive parameter of light-induced damage than morphological examination since light exposures at retinal irradiance levels below the threshold for ultrastructural damage resulted in a temporary BRB dysfunction that could be detected by fluorophotometry but not by the other methods.

Animals↗

PubMed1997

Ultrasound biomicroscopy in the diagnosis of persistent hypotony after vitrectomy.

PURPOSE: To describe a case of persistent hypotony after an otherwise successful vitreous surgery for epiretinal membrane, in which ciliochoroidal detachment was detected by ultrasound biomicroscopy but not by ophthalmoscopy. METHOD: We used ultrasound biomicroscopy to determine the cause of persistent postoperative hypotony. RESULTS: Ultrasound biomicroscopy clearly disclosed ciliochoroidal detachment. In an attempt to resolve ciliochoroidal detachment, we performed vitrectomy and fluid-gas exchange combined with diathermy around the sites of sclerotomy. Postoperatively, the regression of ciliochoroidal detachment was confirmed by ultrasound biomicroscopy. CONCLUSIONS: Using ultrasound biomicroscopy, we were able to visualize ciliochoroidal detachment and its regression clearly, which we had not observed during ophthalmoscopy.

Choroid Diseases↗