Corneal autofluorescence in choroidal melanoma or in choroidal naevus.

AIMS: To investigate whether corneal autofluorescence is different in patients with choroidal melanoma or choroidal naevus. METHODS: Corneal autofluorescence was determined by fluorophotometry in both eyes of 32 patients with a unilateral choroidal melanoma, 32 patients with a unilateral choroidal naevus, and 32 age matched healthy controls. The corneal autofluorescence ratio between affected and contralateral eyes of patients or between randomly selected eyes of healthy controls was calculated. RESULTS: Mean corneal autofluorescence ratio of patients with a choroidal melanoma was significantly higher than that of healthy controls (mean ratio: 1.09 (SD 0.15) and 1.00 (0.09), respectively, ANOVA p=0.014), and than that of patients with choroidal naevus (mean ratio 0.96 (0.09), p<0.001). Mean ratios of patients with choroidal naevus and healthy controls were not significantly different (p=0.27). CONCLUSIONS: Corneal autofluorescence ratio of patients with a unilateral choroidal melanoma is increased. This is probably due to an increased flow of glucose through the impaired blood-aqueous barrier in the affected eye, resulting in additional glycation of corneal proteins and hence in increased autofluorescence. The corneal autofluorescence is not increased in patients with a choroidal naevus, because the blood-aqueous barrier is not impaired in the affected eye in these patients. Measurement of corneal autofluorescence is simple, fast, and non-invasive, and might be helpful to distinguish between patients with choroidal melanoma and those with choroidal naevus.

Lens transmission by fluorophotometry after brachytherapy and thermotherapy of choroidal melanoma.

We studied the effect of transpupillary thermotherapy (TTT) by a diode laser at 810 nm combined with episcleral ruthenium-106 plaque treatment (106Ru) on lens transparency in patients with choroidal melanoma. Lens transmission of blue-green light was measured by fluorophotometry in 17 patients treated with 106Ru treatment and TTT (measured 0.36 years after treatment), 12 patients treated with 106Ru alone (measured 19 years after treatment) and 25 age-matched healthy controls. Differences in lens transmission were not significant between treated and untreated fellow eyes (p > 0.15) nor between patient and control eyes (p > 0.25). TTT of choroidal melanoma combined with 106Ru plaque irradiation did not have a significant effect on the lens transparency up to 6 years after treatment.

The effect of 1% apraclonidine on intraocular pressure after cataract surgery.

BACKGROUND AND OBJECTIVE: To measure the effect of 1% apraclonidine hydrochloride eyedrops on intraocular pressure (IOP) after cataract surgery. The effects of two different dosage regimens, once before surgery or once before and after surgery, were studied. PATIENTS AND METHODS: Patients scheduled for extracapsular cataract extraction and artificial lens implantation were randomly assigned to three groups: group A had a placebo treatment (n = 18), group B had one drop of 1% apraclonidine 1 hour before surgery (n = 16), and group C had one drop of 1% apraclonidine 1 hour before surgery and 1 drop at the end of surgery (n = 17). Two percent hydroxy-propyl-methyl-cellulose was used as the viscoelastic substance. The preoperative IOP and the IOP 6 hours postoperatively in each patient were compared. The paired Student's t test was used to compare IOP before and after surgery. The study design was a randomly assigned, double-masked controlled clinical trial. RESULTS: In group A (placebo) and group B (apraclonidine before surgery), there was a significant increase in IOP (mean IOP increase 11.2 +/- 9.9 mm Hg SD, range -4 to 32, P = .00017, and 9.4 +/- 7.4 mm Hg SD, range -3 to 24, P = .00014, respectively). In group C (apraclonidine 1 hour before and immediately after surgery), the increase in IOP was not significant (mean IOP increase 5.1 +/- 11.5 mm Hg SD, range -10 to 28, P = .084). A postoperative IOP of more than 40 mm Hg applanation tension was reached by two patients in group A, one patient in group B, and two patients in group C. CONCLUSION: Although 1% apraclonidine eye-drops instilled 1 hour before and immediately after extracapsular cataract extraction with artificial lens implantation may help prevent a statistically significant increase in IOP after the operation, 2 of the 17 patients still had IOPs greater than 40 mm Hg 6 hours postoperatively. Apraclonidine applied only before surgery did not prevent a statistically significant increase in IOP.

Long term changes in human corneal endothelium following toxic endothelial cell destruction: a specular microscopic and fluorophotometric study.

AIMS: To investigate the long term relation between corneal thickness, endothelial morphometric variables, and endothelial permeability in patients with endothelial cell counts under 900 cells/mm2 as a result of endothelial cell destruction after cataract surgery. METHODS: Eighteen patients developed the so called toxic endothelial cell destruction (TECD) syndrome following routine cataract surgery because of the intracameral injection of a toxic detergent residue. Ten patients with a mean (SEM) initial cell loss of 72% (2%) were followed for 4 years. Data were obtained at 6 months and 4 years postoperatively and compared between TECD eyes and contralateral control eyes. RESULTS: Mean (SEM) endothelial cell density of the TECD eyes increased from 642 (41) cells/mm2 to 849 (50) cells/mm2 at 4 years postoperatively (p = 0.005). There was no difference in coefficient of variation or percentage hexagonals between 6 months and 4 years postoperatively. Mean (SD) corneal thickness of the TECD eyes and control eyes was similar, 0.51 (0.02) mm and 0.49 (0.01) mm, respectively (p = 0.65). Mean (SD) endothelial permeability was also similar for TECD eyes and control eyes (4.3 (0.9) x 10(-4) cm/min and 4.4 (0.6) x 10(-4) cm/min, respectively (p = 0.57). There was no correlation between endothelial cell density, coefficient of variation, or percentage of hexagonal cells and endothelial permeability in the TECD eyes. In three patients a permanent corneal decompensation occurred. CONCLUSIONS: Four years after TECD corneal endothelial wound healing is stable and the barrier function has been restored.

Endogenous fluorescence of ocular malignant melanomas.

The endogenous fluorescence of human choroid, sclera, and retinal pigment epithelium (RPE) in normal tissue and tissue with uveal melanoma was studied in vitro by a non-invasive and non-destructive fluorescence technique which had previously been applied for the diagnostic evaluation of pigmented lesions of the skin. The fluorescence of the normal choroid is rather dark, the normal sclera exhibits blue fluorescence and the RPE bright yellow fluorescence due to deposits of lipofuscin. In choroidal melanoma, the lipofuscin granulae at the level of the retinal pigment epithelium are cleaved off above the tumour and broken up into small remnants. The fluorescence intensity emitted from the tumour is rather low which agrees with previous findings on skin melanomas. The results may become interesting for diagnostic evaluation of uveal melanomas, uveal naevi, and pigmented conjunctival tumours by endogenous fluorescence.

Corneal metabolism and epithelial barrier function after cataract surgery and intraocular lens implantation: a fluorophotometric study.

PURPOSE: The aim of this study was the assessment of possible changes in corneal metabolism and epithelial barrier function after an extracapsular lens extraction with artificial lens implantation. METHODS: Ten patients without any eye medication were selected out of 140 patients attending for extracapsular lens extraction with lens implantation at the university hospital. Corneal metabolism was evaluated by fluorophotometric measurement of corneal autofluorescence. The corneal fluorescence values were corrected for interference by the fluorescence of the ocular lens. Corneal epithelial barrier function was evaluated by determination of corneal epithelial permeability. The permeability was calculated from the fluorescein penetration into the cornea after application of an eye bath containing fluorescein. Operated and fellow eyes were investigated 1 week before and 3-4 weeks after the operation. RESULTS: The corneal autofluorescence of the operated eye decreased significantly after surgery (mean decrease: 14%, Wilcoxon paired-sample test: P = 0.038). The corneal epithelial permeability of both eyes increased after surgery above the normal range of healthy controls (mean increase operated eye: 34%, P = 0.015, fellow eye: 32%, P = 0.15). Both corneal autofluorescence and epithelial permeability returned to normal values after one year. CONCLUSIONS: The lower corneal autofluorescence in the operated eye after surgery indicates a lower corneal metabolism which may be due to surgery. The increased epithelial permeability of both eyes implies a temporary impairment of the corneal barrier function. The interaction with the fellow eye indicates a consensual reaction which may attributed to damage to the neural system by the surgery.

The blue-green autofluorescence of the human ocular lens after the wear of PMMA contact lenses.

The green ocular lens autofluorescence was determined in 30 Poly Methyl Meth Acrylate (PMMA) contact lens wearing volunteers and compared to that of 21 healthy non-contact lens wearing controls to determine whether a contact lens, reducing UV-A intensity reaching the eye, might protect the ocular lens against cataract formation. Increased autofluorescence was considered an indicator of increased probability for cataract formation. A multiple regression procedure revealed a significant yearly increase of autofluorescence with age (p < 0.01) which did not differ significantly (p > 0.86) from that in the controls. The regression procedure also revealed a decrease of the autofluorescence as a function of contact lens wear, but this decrease was not significant (p = 0.3). The order of magnitude of the decrease (-25%) corresponded to that of the calculated decrease in UV-A intensity at the ocular lens (-39%). This study could not support the thesis that cataract formation can be prevented by wearing PMMA contact lenses.

Blood-retinal barrier dysfunction at the pigment epithelium induced by blue light.

Exposure to low-intensity white light can induce dysfunction of the blood-retinal barrier (BRB) at the retinal pigment epithelium (RPE). To determine whether the shorter wavelengths white light are responsible for this dysfunction, rabbit retinas were exposed to blue light (400-520 nm) or yellow light (510-740 nm). The permeability of the BRB, a parameter for the integrity of the barrier, was quantified with vitreous fluorophotometry. Morphologically, the barrier at the RPE was visualized on light and electron microscopy using horseradish peroxidase (HRP) as a tracer. Seventeen pigmented rabbits were exposed to blue light and 11 were exposed to yellow light. Vitreous fluorescein leakage increased with the exposure energy according to a power function (correlation coefficient > 0.79). The threshold energy for an increase in BRB permeability was 50 J/cm2 (0.014 W/cm2 for 1 hr) after blue and 1600 J/cm2 after yellow light. HRP tracing demonstrated that after blue light exposure, a significant fluorescein leakage on fluorophotometry corresponded to the presence of HRP in the RPE cells and in the subretinal space. After yellow light exposures of < 3700 J/cm2 and in rabbits with no significant fluorescein leakage, the HRP was limited to the choroidal capillaries and Bruch's membrane. These results demonstrate that the blue component of white light causes dysfunction of the BRB at the RPE 30 times more effectively than the longer wavelength fraction of white light. As a result, a blue light blocking filter should be used in ocular surgery on humans when an operating microscope is being used (light power 0.1-0.9 W/cm2).

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.

Xenon arch photocoagulator used for transpupillary hyperthermia.

The technique of near-infrared irradiation to obtain tumour necrosis in experimental pigmented melanomas is described. The xenon arch photocoagulator was modified and adapted for hyperthermia treatment. The adaptations included: filtering the light and changing the electronics, the aiming beam and the diameter of the beam.

Tumor destruction by intermediate level hyperthermia.

The tumoricidal effect of hyperthermia was studied in Greene's amelanotic hamster melanoma transplanted into the anterior chamber of rabbit eyes. To achieve optimal depth penetration, hyperthermia was induced with near infrared light of 820-870 nm, during 15 minutes, at a beam diameter of 2.5-6.0 mm resulting in an intermediate level hyperthermia of 45-60 degrees C. At 45 degrees C no tumor destruction occurred, at 50 degrees C the effect varied from no destruction to total thickness tumor destruction. At 55-60 degrees C total tumor destruction with additional lens damage occurred. In comparison photocoagulation with white light revealed only necrosis up to half the tumor thickness.

Bacteriochlorin a, a new photosensitizer in photodynamic therapy. In vivo results.

The photosensitizing properties of bacteriochlorin a (BCA), a nontoxic derivative of bacteriochlorophyll a, were investigated in vivo. BCA has an absorption band at a wavelength at which tissue penetration is optimal (760 nm), and it shows preferential tumor retention in Greene melanoma implanted in the anterior chamber of rabbit eyes. A dose of 20 mg/kg BCA was administered IV at 4-7 mm tumor diameter; 24 hr later the tumor was irradiated with near-infrared light (30 min, 760 nm, 150-280 J/cm2). On the day after the irradiation it appeared that tumor growth had stopped: fluorescein angiography showed nonperfusion of the tumor. Histopathology after enucleation showed subtotal tumor necrosis with occasionally small clusters of viable cells around a blood vessel and at the tumor periphery. Neither BCA nor light alone had any effect on the eye or melanoma.

Effects of microwave-induced hyperthermia on the anterior segment of healthy rabbit eyes.

Hyperthermia was induced in nine healthy rabbit eyes by means of a microwave 2450 MHz stripline applicator. The anterior segment of each eye was heated to a fixed temperature of between 42 degrees C and 46 degrees C for 30 min. The temperature distribution in the eye was calculated using a thermal model and the actual boundary temperatures and microwave intensity were measured. The effects of treatment were evaluated by daily macroscopic examination, fluorescein angiography and fluorophotometry, as well as by histology. Histological examination of changes induced by this hyperthermic delivery system revealed a sharp transition at 44 degrees-45 degrees C from no permanent damage to the anterior chamber at lower temperatures to serious damage such as local necrosis, pigment disruption and local cataract at high temperatures. A sharp transition in the same temperature range was observed in vivo in the fluorescein leakage of the iris vessels by comparative fluorescein angiography and by anterior segment fluorophotometry.

Scintimetric detection of choroidal malignant melanoma with [123I]-5-iodo-2-thiouracil.

[123I]-5-iodo-2-thiouracil (123I-ITU) was evaluated as a radiopharmaceutical for tumor detection in 10 patients with proven choroidal melanoma. Uptake of 123I-ITU was measured with a specially designed single eye probe collimator, 24 h after administration of 123I-ITU. Increased uptake in the tumor-bearing eye as compared to the fellow nontumor bearing eye was found in 7 out of 10 cases when the probe was located 3.5 cm in front of the eye (p less than 0.01). By using a double pinhole collimator tests were positive in 3 out of 10 123I-ITU studies only. Tests with 123I-ITU were compared with 67Ga tests in the same patients. The 67Ga tests with the single eye probe collimator were positive in 6 out 10 cases when the probe was located 6 cm in front of the eye. With the double pinhole collimator tests were positive in 7 out of 10 67Ga studies. It is concluded that 123I-labeled thiouracil is at least as useful as a radiopharmaceutical for ocular melanoma diagnosis as 67Ga-citrate, provided measurements are performed with a single eye probe.

Kinetics of reduction of the oxidized primary electron donor of photosystem II in spinach chloroplasts and in Chlorella cells in the microsecond and nanosecond time ranges following flash excitation.

Absorption changes (deltaA) at 820 nm, following laser flash excitation of spinach chloroplasts and Chlorella cells, were studied in order to obtain information on the reduction time of the photooxidized primary donor of Photosystem II at physiological temperatures. In the microsecond time range the difference spectrum of deltaA between 750 and 900 nm represents a peak at 820 nm, attributable to a radical-cation of chlorophyll a. In untreated dark-adapted material the signal can be attributed solely to P+-700; it decays in a polyphasic manner with half-times of 17 microseconds, 210 microseconds and over 1 ms. The oxidized primary donor of Photosystem II (P+II) is not detected with a time resolution of 3 microseconds. After treatment with 3--10 mM hydroxylamine, which inhibits the donor side of Photosystem II, P+II is observed and decays biphasically (a major phase with t1/2=20--40 microseconds, and a minor phase with t1/2 congruent to 200 microseconds), probably by reduction by an accessory electron donor. In the nanosecond range, which was made accessible by a new fast-response flash photometer operating at 820 nm, it was found the P+II is reduced with a half-time of 25--45 ns in untreated dark-adapted chloroplasts. It is assumed that the normal secondary electron donor is responsible for this fast reduction.