The purpose of the present work was to increase the understanding of the toxic effects of ultraviolet radiation on the lens. A high-pressure mercury arc source with collimating optics, an interference filter (Tmax = 300 nm, T0.5 = 10 nm) and projecting optics was employed for experimental exposure of animals. Irradiance was measured with a calibrated photodiode. A device for objective absolute measurement of light dissemination in rat lenses was developed and characterized on a reference sample of lenses from healthy rats. A tolerance limit for non-pathological was set on a statistical basis. A method for preparing lens samples for atomic absorption spectrophotometry was developed and characterized. In vivo exposure of rat lenses to 6 kJ/m2 induced unscheduled DNA synthesis and reduced scheduled DNA synthesis. Microscopic observation, with a phase contrast microscope, of rat lenses demonstrated that in vitro exposure to 0.72 and 2.9 kJ/m2 evoked anatomical alterations in the lens epithelial cells and accelerated the swelling observed in incubated lenses. Lenses exposed to 36 kJ/m2 in vivo opacified completely in one week. The exclusively white opacification started at the anterior surface. As observed light and electron microscopically the lens cells swelled, starting in the epithelium and thereafter involving first the anterior cortex, later the posterior cortex and finally, within a week after exposure, the outer nuclear region. Light dissemination in the lens after exposure to 30 kJ/m2 increased exponentially with a 5.5 h latency before onset, and a time constant of 19 h. The water mass in the same lenses increased transiently with a maximum 24 h after exposure. The expected increase in lens dry mass due to growth did not take place. Rabbit lenses were incubated after exposure in vitro to 0.6, 3.0 and 6.0 kJ/m2, respectively. The two higher doses induced quicker mass gain in exposed lenses than in their non-exposed contralaterals. There is an increase in sodium in lenses exposed to 30 kJ/m2 and a simultaneous decrease in potassium. The sodium increased exponentially with a 6.6 h latency before onset, and a time constant of 38 h. A slight increase in light dissemination and in sodium per dry mass was noted even in the non-exposed lenses contralateral to those exposed. The data collected suggest that the opacification seen after a high-dose exposure of the lens to 300 nm UVR in vivo occurs as a result of osmotic swelling.
A retinoblastoma-like tumour has been established and characterized in terms of growth rates in vitro and in vivo, and by histopathology and chromosome analysis. Injected tumour cells grew regularly in the vitreous body with a blood supply from the retinal vessels. The tumour tissue was histopathologically similar to that of anaplastic human retinoblastomas. Almost all the cells had a triploid chromosome number and the DNA amount in tumours was stable, suggesting a stable tumour system without drift against more anaplastic degrees. Tumour cells plated in culture flasks were grown in colonies. Evaluation of the number of clonogenic cells in treated, relative to non-treated flasks reflected a quantitative treatment response. When the cells were injected into the eyes of young rats, solid tumors were formed which grew regularly until perforation of the globes. The tumours were suitable for assessment of therapeutic response in terms of local tumour control after treatment. Photodynamic therapy (PDT) of cancers, using hematoporphyrin derivatives (HPD) and visible light, is a therapeutic modality where HPD is administered 1-5 days before local light irradiation of the tumour. The combination of HPD, light energy and oxygen produces the cytotoxic agent singlet oxygen which only exists in its active state for a few milliseconds. Using this modality, it may be possible to obtain local tumour destruction in light-irradiated areas and avoid spreading of the cytotoxic agents to other organs. The effect of PDT with purified HPD (Photofrin II) and red light has been evaluated in the characterized retinoblastoma-like tumour in vivo and in vitro. The experiments demonstrated that Photofrin II and red light destroys cells in tissue culture flasks. Local control of intraocular retinoblastoma-like tumours was obtained in up to 33% of the animals following a single treatment. Adverse effects in the present model were corneal and conjunctival damage. Generally, the effect of PDT increased with larger Photofrin II doses, higher energy doses or a shorter time interval between drug administration and light irradiation. Damage to the cornea or conjunctiva limited the maximum tolerable treatment doses in the present model. The experiments suggests that PDT is a safer treatment with Photofrin II 2.5 mg/kg and a high light energy dose than with 10 mg/kg and an equivalent lower light energy dose. In tissue culture flasks, the cell inactivation did not depend on the light energy rate but only on the total delivered energy dose. The cells had a low capacity to repair sublethal damage.(ABSTRACT TRUNCATED AT 400 WORDS)
Two-hundred-seventy-eight retinoblastoma tumors in 169 patients were photocoagulated by one of two doctors with the xenon arc photocoagulator. More than 70% of tumors treated were cured by photocoagulation. The following features correlated with success: 1) size of the tumor, 2) location of the tumor and 3) elevation of the tumor. Seventy of 72 tumors (97%) up to 1 dd in size were cured while only 9 of 22 (41%) tumors larger than 5 dd were cured. The mean size of tumors cured was 2 dd, while the mean size of those that failed was 3.9 dd. Tumors located anterior to the equator were more often successfully treated (67/81 = 83%) than those posterior to the equator (44/74 = 60%). Tumors with the height equal to half the base were classified as 'low elevation', while those with heights larger than half the base diameter were classified as high elevation. Tumors with low elevation did significantly better (162/201 = 81%) than those with high elevation (33/76 = 43%). No correlation was found between success and the following features: age at diagnosis, sex, age at first photocoagulation, eye involved (right or left), time from radiation to first light coagulation, nasal versus temporal tumors or the clock hour of the tumor or category of tumor independent of size of location. Forty-four percent of tumors that failed photocoagulation went on to develop vitreous seeding and 55% required enucleation. Fifty percent of the eyes that were treated initially with photocoagulation went on to develop new tumor foci elsewhere in the eye. In all cases the new tumors appeared anterior to the equator. The children who developed additional tumors in the eye were younger (5.5 months) when photocoagulated than those who did not develop additional tumors (47.75 months). Photocoagulated retinoblastomas must be followed for at least three years before a cure is certain.
One eye of 27 patients with keratoconus and 37 normals were examined by photokeratoscopy and topographic pachometry to obtain informations about the corneal shape and thickness profile. The progressive alteration of corneal topography in keratoconus may be based on elastic deformation. Through a distention, predominantly of the central area, increasing large differences between central and peripheral thickness appear. Simultaneously the area of the corneal surface increases into a more elliptical corneal shape. In keratoconus relative to normals, the study demonstrates, an alteration of, as well as a correlation between, the corneal shape and thickness profile in accordance with the elastic hypothesis. Based on corneal topography determination, intraocular pressure measurements and a derived elastic theory the corneal tissue mass (M), tissue strength (Young's Modulus in steady state Y(s) , and the ocular rigidity (E) were determined. Y(s) and E was found to be significantly decreased, whereas M seems to be equal in keratoconus compared with normals. Histologically cornea consists of an amorphous matrix in which the collagen fibers are embedded. E seems to reflect the immediate elastic response of the collagen fibers (Y(i], which, however, may be relaxed in steady state. Y(s) seems to reflect the elastic response of the matrix, which consists of matrix compression and sliding of collagen fibers. Thus the biomechanical alteration of cornea in keratoconus may be introduced by increased sliding fo collagen fibers due to reduced attachment to Bowman's layer and altered synthesis of the matrix substance.