George R. Merriam

Accelerated heavy particles and the lens. III. Cataract enhancement by dose fractionation

For a number of biological end points it has been shown that, in contrast to low linear energy transfer (LET) radiation, dose fractionation of high-LET radiation does not result in a reduction in overall effectiveness. Studies were conducted to determine the effect of fractionating the exposures to heavy ion doses on the development of cataracts. Rat eyes were exposed to single doses of 1, 5, and 25 cGy of 570 MeV/amu40Ar ions and to 2, 4, and 10 Gy of 250 kVp X rays. These were compared to unirradiated controls and eyes which were exposed to the same total dose delivered in four fractions over 12 h. While in all cases fractionation of the exposure to X rays produced significant reduction in cataractogenic potential, fractionating doses of 40Ar ions caused a dose- and stage-dependent enhancement in the development of cataracts.

Accelerated Heavy Particles and the Lens: I. Cataractogenic Potential

The effect of varying doses of accelerated (570 MeV/ amu ) argon ions on the rat lens is described with detailed observations on the sequence of development of the cataracts, the time-dose relationship, and the analysis of their cataractogenic potential. The relative biological effectiveness (RBE) of the heavy particles for cataract production, compared to low linear energy transfer (LET) radiation (X rays), has been established. These data indicate that, as with neutrons, the RBE increases with decreasing dose and that at a dose of 0.05 Gy an RBE of about 40 was observed.

The Conjunctival Epithelium

Histochemical analysis indicates that rat and human conjunctival goblet cells contain a sialo-mucin which is susceptible to sialidase digestion. Electron microscopic studies demonstrate some ultrastru

Postoperative irradiation for pterygium: guidelines for optimal treatment.

PURPOSE Postoperative adjuvant strontium-90 beta-ray therapy is a proven technique for reducing the recurrence rate of pterygium. A wide variety of doses and fractionation schemes have been used in the application of the radiation. There have been recent reports of significant rates of late-occurring complications after single-fractioned treatment. Compared with a single-dose application, fractionation would only offer a therapeutic benefit if recurrence prevention were an early-responding tissue phenomenon, in contrast to late-responding sequellae. We investigate this point with a view to elucidating better treatment protocols for postoperative beta-ray therapy for pterygium. METHODS AND MATERIALS We use the linear-quadratic formalism to analyze published nonrecurrence rates, as a function of dose and fraction number, to obtain a value for the parameter alpha/beta, which is an indicator of whether nonrecurrence is an early or late-responding phenomenon. RESULTS The estimated value of the linear-quadratic parameter, alpha/beta, is 25 Gy, with 90% confidence limits of +/- 9 Gy. This large value unequivocally suggests that nonrecurrence is an early responding phenomenon, implying that fractionation should give an increased therapeutic ratio between nonrecurrence and late sequellae. CONCLUSIONS Compared with a single-fractioned treatment, an improved therapeutic ratio (nonrecurrence vs. complications) would be expected from fractionated application of the beta-ray therapy. Given the parameters obtained from fitting literature data, we calculate guidelines for the dose/fraction schemes that should give equivalent disease control to different single-fraction applications, but should reduce the incidence of late-occurring sequellae.

The Lens Epithelium and Radiation Cataracts II. Interphase Death in the Meridional Rows

X irradiation of the lens of a young rat with doses exceeding 2 Gy (200 rad) causes the fragmentation of the nuclei of some of the cells of the meridional rows (MR). The karyopyknosis, which seems ...

G₀/G1 Arrest of Cell Proliferation in the Ocular Lens Prevents Development of Radiation Cataract

Exposure of the eyes of young frogs and rats to X-rays (12–25 Gy) causes posterior cataracts to appear several weeks later. Hypophysectomized frogs do not develop these opacities, but hypophysectomized rats do. In the former, but not the latter animals, the operation completely stops lens mitosis, the epithelial cells being largely confined to the G₀/ G1 phase of the cell cycle.

Hypophysectomy exerts a radioprotective effect on frog lens.

Exposure to X-rays usually causes cataracts in frogs. These cataracts are always preceded by misalignment of the structures called meridional rows (MR). When cell division is completely halted by hypophysectomy, however, irradiation no longer disturbs the orientation of the MR. Since the MR are the structures formed as lens epithelial cells differentiate into lens fibres it is reasonable to propose that radiocataractogenesis depends upon a mitosis-driven formation of pathological fibres from epithelial cells that have been rendered abnormal by exposure to X-rays.

The lens epithelium and radiation cataract. III. The influence of age on the nuclear fragmentation of the meridional row cells following X irradiation.

Studies were conducted on the effect of age on the production of fragmented nuclei in meridional row (MR) cells following ocular exposure to x radiation. It was found that vulnerability to such damage is maximal approximately 4 weeks postpartum in rats, and that increasingly larger doses of x rays were required to produce equal responses in older animals. Studies on other animals (mice, rabbits, frogs) thought to be resistant to this injury indicate that the failure to see this pathological change in those species is related to age. Although its role in cataractogenesis is unclear, direct damage to the nuclei of MR cells may be ubiquitous among animals susceptible to radiation cataract development.

The role of inflammation in radiation cataractogenesis.

Studies were designed to assess the contribution of X-ray-induced intraocular inflammation to radiation cataractogenesis in the rat and the rabbit eye. In the rat it was observed that only X-ray. doses exceedign 18 Gy† produced ocular changes consistent with uveitis beginning 1–4 days post-irradiation. Low to moderate cataractogenic doses failed to produce such changes. In the rabbit eye a 10 Gy single dose of X-rays induced inflammation and cataract. The same dose when divided into ten 1 Gy daily fractions was non-inflammatory yet produced cataracts similar in appearance and time of onset to that induced by a single tenfold higher X-ray dose. These and additional studies using endotoxin-induced uveitis suggest that inflammation is not essential to the development of X-ray cataract.

Scanning Electron Microscopic Analysis of Radiation Cataracts in Rat Lenses

Cataracts produced in 4-week-old rats following exposure of the eye to various doses of 185 kVp X-rays, were analyzed 45 days after irradiation by scanning electron microscopy (SEM), as well as by conventional light microscopy (LM). The severity and extent of the ultrastructural damage seen at the LM and SEM levels varied as an increasing function of dose and correlated well with the clinical changes which were scored by slitlamp biomicroscopy prior to preparation. In the early-stage low-dose cataracts, damage was generally limited to the equatorial and posterior subcapsular regions. The late-stage high-dose cataracts were associated with clusters of 4 to 10 μm globules at the poles subcapsularly, massive disruption of the equatorial region and the formation of a granular matrix which extended to the posterior pole. Ultrastructural changes were also noted in the superficial cortical region, while the lenticular nucleus and the residium of the cortex remained unchanged.