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Accuracy and reliability of remote retinopathy of prematurity diagnosis.

OBJECTIVE: To determine the accuracy and reliability of retinopathy of prematurity (ROP) diagnosis using remote review of digital images by 3 masked ophthalmologist readers. METHODS: An atlas was compiled of 410 retinal photographs from 163 eyes of 64 low-birth-weight infants taken using a wide-angle digital fundus camera. All the images were independently reviewed by 3 readers, and the diagnosis in each eye was classified into 1 of 4 ordinal categories: no ROP, mild ROP, type 2 prethreshold ROP, or ROP requiring treatment. Findings were compared with a reference standard of dilated indirect ophthalmoscopy with scleral depression performed by an experienced pediatric ophthalmologist. RESULTS: Sensitivities/specificities of the diagnosis of any ROP were 0.845/0.910 for the first reader, 0.816/0.955 for the second reader, and 0.864/0.493 for the third reader. Sensitivities/specificities of the diagnosis of ROP requiring treatment were 0.850/0.960 for the first reader, 0.850/0.973 for the second reader, and 0.900/0.953 for the third reader. When ROP was classified into ordinal categories, the overall weighted kappa for interreader reliability was 0.743. Intrareader reliability for detection of low-risk prethreshold ROP or worse was 100% for all readers. CONCLUSION: The accuracy, interreader reliability, and intrareader reliability of remote diagnosis of clinically relevant ROP based on digital imaging are substantial.

Birth Weight↗

Ocular toxoplasmosis and Hodgkin's disease: report of two cases.

Isolated ocular toxoplasmosis developed in two patients with Hodgkin's disease. The diagnosis was made by ophthalmoscopy of the fundus, serologic tests, and evolution. This raises the possibility that Toxoplasma infection and the localization of retinochoroiditic lesions on the macula could be the results of the immunosuppression associated with Hodgkin's disease.

Adolescent↗

Degenerative changes in retinal vessels. Photodocumentation with monochromatic filters.

The appearance of certain ocular structure changes due to changes in absorption, reflection, and optical transmission depends on the wavelength of light. By means of this physical quality of the light, it is possible to demonstrate certain parts of the fundus better than others. Several examples described in this article demonstrate how degenerative vascular alterations can be judged much better and more safely by use of monochromatic light and light of varying wavelengths. Alterations of blood vessel caliber show the most contrast in yellow-green light where there is maximum absorption by the blood. Alterations in blood vessel wall reflection that are invisible in white light can be demonstrated in short-wave light and also partially in red light. Ophthalmoscopy in connection with the xenon arc lamp as a method of examination is suprior to photography alone.

Color↗

Toxicity, efficacy, and clearance of intravitreally injected of cefazolin.

The intravitreal injection of cefazolin sodium was evaluated with respect to its potential toxicity, efficacy, and clearance in the treatment of bacterial endophthalmitis in the rabbit model. Toxicity evaluation included indirect ophthalmoscopy, scotopic electroretinogram, and light microscopy of histopathologic specimens. Rabbits given doses up to and including 2.25 mg of cefazolin sodium showed no evidence of toxic reaction by these criteria after two weeks of observation. When injected within 24 hours of inoculation, 2.25 mg of cefazolin sodium sterilized five of six rabbit eyes infected with Staphylococcus aureus. Following intravitreal injection of 2.25 mg of cefazolin sodium, vitreous concentrations in excess of the minimum inhibitory concentration for S aureus were maintained for five days. A 2.25-mg dose of cefazolin sodium appears to be nontoxic, effective, and biologically active against susceptible organisms during a prolonged period, when injected into the vitreous cavity of the pigmented rabbit in vivo.

Animals↗

Fundus changes following faden operation.

A faden operation was performed in 187 eyes that were studied by indirect binocular ophthalmoscopy at regular intervals after the surgical procedure. Of these eyes, 29 (15.5%) showed ocular fundus abnormalities, with 28 cases of chorioretinal scars at the level of the muscle scleral anchorage and one case of Herpburn-Amalric triangular syndrome of choroidal ischemia. No case of retinal tears was found in this series. Fundus changes are by far the most frequent complication of the faden operation, and to our knowledge, this has not been previously described. The findings of the present study suggest (1) the necessity of routine ophthalmoscopic controls in the postoperative stage regarding those eyes in which the faden operation has been performed, and (2) that the faden operation on the lateral rectus muscle is seriously contraindicated because of the high risk of irreversible macular damage consecutive to these chorioretinal lesions.

Adolescent↗

Retinal toxicity of recombinant tissue plasminogen activator in the rabbit.

We studied the dose-dependent retinal toxicity of the available commercial preparation of human recombinant tissue plasminogen activator in the normal rabbit eye. Tissue plasminogen activator was injected into the midvitreous cavity of albino rabbits in doses (per 100 microL) of 25, 50, 75, and 100 micrograms. Control eyes received 100 microL of balanced salt solution or tissue plasminogen activator vehicle. No evidence of a retinal toxic reaction was seen in eyes receiving 25 micrograms of tissue plasminogen activator. One of four eyes injected with 50 micrograms showed loss of photoreceptor cells by light microscopy. Severe retinal damage was seen by ophthalmoscopy, electroretinography, and light microscopy in three of four eyes receiving 75 micrograms of tissue plasminogen activator and in all eyes treated with 100 micrograms of tissue plasminogen activator or equivalent vehicle. These results suggest that the commercial recombinant tissue plasminogen activator formulation has a narrow margin of safety in nonvitrectomized eyes and that a component of the vehicle is the toxic factor.

Animals↗

Noncontact transscleral neodymium-YAG laser photocoagulation of the pigmented rabbit retina.

We studied the applicability of transscleral delivery of noncontact neodymium-YAG laser in its free-running mode (10 milliseconds) in creating chorioretinal lesions in 16 rabbits. After the laser was applied, the eyes were studied by indirect ophthalmoscopy, light microscopy, and electron microscopy. Lesions generated with low-energy and defocus settings were characterized by intact sclera, variable clumping of the pigmented choroidal lamellae, destruction of choriocapillaris, and loss of the retinal pigment epithelium. In the central region of laser exposure, vacuolization of the retinal pigment epithelium and outer retina were observed. No scleral changes were noted. In contrast with lesions produced with high-energy and/or high-defocus settings, these lesions were produced without hemorrhagic phenomena or breaks in the neurosensory retina. These data demonstrate that noncontact transscleral neodymium-YAG photocoagulation is capable of very localized, selective destruction of the retina and choroid and deserves further study.

Animals↗

Microwave diathermy of the retina and choroid.

Microwaves were used to induce chorioretinal scar formation in normal rabbit eyes. We have developed a directional 6.8-gigahertz microwave applicator with a rectangular aperture. It was designed to mimic the shape and function of a T-shaped scleral depressor. For treatment, the applicator was placed on the conjunctiva over the sclera. Then, indentation was used to visualize probe placement during indirect ophthalmoscopy. Thermocouple-controlled heating was initiated such that conjunctival temperatures in a range of 51 degrees C to 65 degrees C were induced for 10 seconds per treatment. We found that treatment at temperatures of 51 degrees C or 52 degrees C for 10 seconds produced circular areas of acute retinal whitening. From these microwave-induced lesions, there evolved chorioretinal attenuation with and without evidence of retinal pigment epithelial hyperplasia. No evidence of scleral damage was noted at these thermal doses.

Animals↗

An eye for an eye. A simplified model for teaching.

We developed an easily constructed, inexpensive eye model that consists of a Styrofoam head carved out to house a slide holder, a wide-angle, clinical photographic fundus slide, a plastic face, and an anatomically correct eye. The model can be used by students and residents to learn direct and indirect ophthalmoscopy, fundus photography, and laser photocoagulation. This model gives students and residents a realistic learning experience without inconveniencing or endangering patients.

Eye↗

Bubble formation as primary interaction mechanism in retinal laser exposure with 200-ns laser pulses.

BACKGROUND AND OBJECTIVE: Retinal laser photocoagulation is generally performed by laser pulses of a few hundred milliseconds. The tissue interaction mechanism is a pure thermal interaction mechanism. As pulse duration gets shorter, different, non-thermal interaction mechanisms start to appear. The time domain for a change of tissue interaction mechanism seems to be in the ns and micros range. The goal of this study was to characterize the tissue interaction mechanism with 200-ns laser pulses, which approximate the thermal relaxation time of single melanin granules. MATERIALS AND METHODS: The retinas of 19 eyes of 10 rabbits were irradiated by 10 and 500 repetitive laser pulses (wavelength, 532 nm; repetition rate, 500 Hz; pulse duration, 200 ns; per pulse energy, 0-120 microJ; retinal spot size, 100 microm). The effects were evaluated by fluorescein angiography, ophthalmoscopy and by theoretical thermal calculations. Light microscopy and transmission electron microscopy were additionally performed on lesions irradiated by 500 pulses. RESULTS: Single pulse threshold energies for angiographic visibility were 3.5 microJ (10 pulses) and 2.1 microJ (500 pulses), for ophthalmoscopic visibility 9.0 microJ (10 pulses) vs. 8.6 microJ (500 pulses). At energy levels above ophthalmoscopic visibility macroscopically visible bubble formation inside the retina could be observed. This occurred at energy levels of 35 microJ (10 pulses) vs. 17 microJ (500 pulses). Microscopic evaluation of lesions irradiated with 500 pulses and energies at the angiographic threshold showed a damage primarily to the RPE. Additional outer segment damage of the photoreceptors could be found. A gap between damaged RPE cells and the outer segments could be repeatedly found as well as damaged RPE cells, which were detached from intact Bruch's membrane. Temperature calculation shows that temperatures above 100 degrees C may exist around single melanin granules. CONCLUSION: The studies suggest that RPE damage may occur by bubble formation around single melanin granules.

Animals↗

Simultaneous three wavelength imaging with a scanning laser ophthalmoscope.

BACKGROUND: Various imaging properties of scanning laser ophthalmoscopes (SLO) such as contrast or depth discrimination, are superior to those of the traditional photographic fundus camera. However, most SLO are monochromatic whereas photographic systems produce colour images, which inherently contain information over a broad wavelength range. METHODS: An SLO system has been modified to allow simultaneous three channel imaging. Laser light sources in the visible and infrared spectrum were concurrently launched into the system. Using different wavelength triads, digital fundus images were acquired at high frame rates. RESULTS: Favourable wavelengths combinations were established and high contrast, true (red, green, blue) or false (red, green, infrared) colour images of the retina were recorded. The monochromatic frames which form the colour image exhibit improved distinctness of different retinal structures such as the nerve fibre layer, the blood vessels, and the choroid. CONCLUSIONS: A multi-channel SLO combines the advantageous imaging properties of a tunable, monochrome SLO with the benefits and convenience of colour ophthalmoscopy. The options to modify parameters such as wavelength, intensity, gain, beam profile, aperture sizes, independently for every channel assign a high degree of versatility to the system.

Color↗

Treatment of vascular retinopathies with Pycnogenol.

The aim of our study was to investigate the effects of Pycnogenol on the progression of diabetic retinopathy and other vascular retinal disorders. The study consisted of a double-blind phase in which 20 patients were recruited and randomly treated with placebo or Pycnogenol (50 mg x 3/day for 2 months) and an open phase in which another 20 patients were treated with Pycnogenol at the same dose schedule. In total, 40 patients with diabetes, atherosclerosis and other vascular diseases involving the retina were enrolled; 30 of them were treated with Pycnogenol and 10 with placebo. The results demonstrated a beneficial effect of Pycnogenol on the progression of retinopathy. Without any treatment (placebo) the retinopathy progressively worsened during the trial and the visual acuity significantly decreased; on the contrary, the Pycnogenol-treated patients showed no deterioration of retinal function and a significant recovery of visual acuity was also obtained. The fluorangiography showed an improvement of retinal vascularization and a reduced endothelial permeability and leakage in the Pycnogenol, but not in the placebo-treated, patients. The ophthalmoscopy and the electroretinogram (ERG) also confirmed the beneficial effects of Pycnogenol. The mechanism of action of Pycnogenol may be related to its free radical (FR) scavenging, anti-inflammatory and capillary protective activities. It has been suggested that Pycnogenol may bind to the blood vessel wall proteins and mucopolysaccharides and produce a capillary 'sealing' effect, leading to a reduced capillary permeability and oedema formation.

Diabetic Retinopathy↗

Diode laser photocoagulation of choroidal hemangioma.

BACKGROUND: The argon laser photocoagulation has recently become the treatment of choice in choroidal hemangioma. We evaluated the efficacy of the near infrared wavelength diode laser in the treatment of such tumours. This wavelength is not highly absorbed by the retinal pigment epithelium and penetrates deep into the choroid. METHODS: Two cases of choroidal haemangioma with a serous detachment of the neural retina were diagnosed with ophthalmoscopy, fluorescein and indocyanine green angiography, A-scan and B-scan ultrasonography and treated with a surface photocoagulation with a diode laser. The efficacy of photocoagulation was evaluated three, six, twelve and fifteen months after laser treatment. RESULTS: The resorption of the subretinal fluid and a reduction in thickness of the tumour followed laser photocoagulation. CONCLUSIONS: Diode lasers might be effective in the treatment of choroidal haemangioma.

Aged↗

Retinal hemorrhages in malignant arterial hypertension.

We conducted a detailed investigation into retinal hemorrhages in renovascular malignant arterial hypertension experimentally produced in rhesus monkeys. The hypertension was produced by modified Goldblatt's procedures in 60 rhesus monkeys and hypertensive fundus changes were studied by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography. Our study revealed that, in hypertensive retinopathy due to malignant hypertension, retinal hemorrhages usually did not constitute either one of the earliest or one of the most conspicuous retinal lesions, but, on the contrary, were a minor feature of the retinopathy. Neither the time of onset of retinal hemorrhages nor their peak severity showed any significant correlation with the level of the arterial hypertension. The hemorrhages were usually situated in the nerve fiber layer, and could be located anywhere in the fundus but were usually found in the distribution of the radial peripapillary retinal capillaries. There was no association between the presence of retinal hemorrhages and retinal venous changes; the latter were seen only in a minority of animals and consisted of retinal venous stasis, venous collaterals and arteriovenous shunts.

Animals↗

Hereditary retinal degeneration in the Abyssinian cat: correlation of ophthalmoscopic and electroretinographic findings.

Ophthalmoscopic and electroretinographic (ERG) findings were correlated in a group of Abyssinian cats affected by a slowly progressive and hereditary retinal degenerative disease. According to ophthalmoscopic findings the disease was divided into stages. At stage 1 and 2 retinal changes were minor; showing a gray discoloration most often in the peripheral and midperipheral tapetal fundus. At stage 3 discoloration was generalized and there was marked vascular attenuation. A generalized retinal atrophy was found at stage 4. ERG recordings showed an abnormally depressed stimulus response curve for the b-wave at stage 1 of disease when 30-Hz cone flicker responses were indistinguishable from normal. With progression of disease there was a successive decrease of a- and b-wave amplitudes before there was a significant reduction also of the c-wave amplitude (first seen at stage 3). The ERG was nonrecordable at stage 4. These findings suggest that the photoreceptors are affected primarily by the disease, before there is a functional involvement also of the pigment epithelium. The rod system seems to be affected early in the disease as compared with the cone system. A staging of the disease by ophthalmoscopy correlated more to the function of the rods than to that of the cones.

Animals↗

Determination of the neuroretinal rim area using the horizontal and vertical disc and cup diameters.

BACKGROUND: This study evaluated whether the neuroretinal rim area can be calculated on the basis of the horizontal and vertical diameters of the optic disc and cup applying the formula of an ellipse. METHODS: Color stereo optic disc photographs of 587 normal subjects and 1193 patients with glaucoma were morphometrically examined. In a first method, the areas of the optic disc and cup were planimetrically measured and the area of the neuroretinal rim was determined as optic disc area minus cup area. In a second method, the optic disc and cup were assumed to have an elliptical shape. Their areas were calculated by applying the formula of an ellipse, taking into account their horizontal and vertical diameters. As in the first method, the rim area was then determined as disc area minus cup area. RESULTS: The values of the neuroretinal rim area as measured using the first method differed by 0.05 +/- 0.05 mm2 from the values as calculated by the second method. The average error was 2.8 +/- 2.9% for the normal group and 8.2 +/- 20.8% for the glaucoma patients. It increased with decreasing neuroretinal rim area and increasing mean visual field defect. CONCLUSIONS: For clinical purposes, the neuroretinal rim area can be determined on the basis of the horizontal and vertical diameters of the optic disc and cup. The horizontal and vertical disc and cup diameters being determinable upon ophthalmoscopy, this finding is important for the direct measurement of optic disc morphology during any ophthalmoscopic examination.

Adolescent↗

Toxicity of 1-(beta-D-arabinofuranosyl)cytosine after intravitreal injection in the rabbit eye.

The retinal toxicity of intravitreally injected 1-(beta-D-arabinofuranosyl)cytosine (cytarabine) was examined in 7 chinchilla rabbits to determine if cytarabine can be used as local therapy for vitreoretinal non-Hodgkin's lymphoma. Fractionated dose of 600 micrograms, 1500 micrograms, and 2700 micrograms cytarabine in stabilized saline were given intravitreally in one eye (2 x 300 micrograms, 5 x 300 micrograms, and 3 x 900 micrograms, respectively, with an interval time of 24 h) and stabilized saline in the other eye as control. Toxic effects were evaluated with biomicroscopy, direct ophthalmoscopy, fluorophotometry, electroretinography, light, and electron microscopy. Toxic effects were found with the 1500 micrograms and 2700 micrograms doses only. They consisted of a temporary impairment of the blood retina barrier function for fluorescein as measured by fluorophotometry and an irreversible change of the b-wave in the electroretinograms. No histopathologic changes were seen under the light microscope. Electron microscopic examination showed aberrations in the synaptic pedicles of the photoreceptor cells at a dose of 1500 micrograms cytarabine. The results suggest that the cytarabine dose that is expected to be therapeutic for vitreoretinal non-Hodgkin's lymphoma (about 90 micrograms given in three doses of 30 micrograms) is non-toxic for ocular structures.

Animals↗

Endothelin-1 immunoreactivity in plasma is elevated in HIV-1 infected patients with retinal microangiopathic syndrome.

Endothelin-1 is a recently identified cytokine with potent vasoconstrictor activity which is associated with various diseases involving blood vessels. HIV-1 related retinal microangiopathic syndrome is a frequent finding in patients with AIDS or AIDS-related complex, presenting predominantly with retinal cotton-wool spots. We investigated 55 HIV-1 infected patients by ophthalmoscopy and for endothelin-1 immunoreactivity in plasma and an additional 76 HIV-1 infected patients only for endothelin-1 levels. For reference values 13 age-matched healthy subjects were studied. In 18 of 55 patients (33%) investigated ophthalmoscopically we found evidence of microangiopathic syndrome. Overall, the mean endothelin-1 immunoreactivity in plasma of HIV-1 infected patients was significantly elevated as compared to controls (4.28 +/- 3.62 versus 2.72 +/- 0.67 fmol/ml, P < 0.0001). HIV-1 infected patients with retinal microangiopathic syndrome had significantly higher plasma levels of endothelin-1 immunoreactivity (4.59 +/- 1.38 fmol/ml) compared to HIV-1 infected patients without microangiopathic syndrome (3.18 +/- 1.64 fmol/ml, P = 0.003). Correlation analysis revealed that endothelin-1 immunoreactivity in plasma had no significant association with disease progression, CD4 cell count, beta 2-microglobulin, neopterin, or age. Endothelin-1 immunoreactivity in plasma was correlated exclusively with retinal microangiopathic syndrome in one or both eyes (r = 0.45, P = 0.0006) and with the number of cotton-wool spots (r = 0.50, P = 0.0001). In conclusion, HIV-1 related retinal microangiopathic syndrome is associated with elevated plasma levels of endothelin-1. By virtue of its potent vasoconstrictor activity endothelin-1 may be involved in the pathogenesis of HIV-1 related vascular disease.

Adult↗