Proton therapy of iris melanoma with 50 CGE : Influence of target volume on clinical outcome.

PURPOSE: The aim of this study was to evaluate local tumour control, incidence of radiation-induced glaucoma and associated interventions of sector-based and whole anterior segment proton beam therapy (PBT) for the treatment of iris melanoma. PATIENTS AND METHODS: We retrospectively analysed the data of 77 patients with iris melanoma who underwent PBT applied as 50 CGE in four daily fractions. Of the patients, 47 received PBT with a circular-shaped collimator and 30 with a conformal sector-shaped target volume. Local control, eye preservation and secondary glaucoma were evaluated. RESULTS: Median follow-up time was 54.9 months. Local tumour control was 100% in patients receiving whole anterior segment irradiation. Two patients developed pigment dispersion in the non-irradiated area after sector-based PBT and received whole anterior segment salvage PBT. The mean volume of ciliary body irradiated was 89.0% and 34.9% for whole anterior segment and lesion-based irradiation, respectively. At the end of follow-up, secondary glaucoma was found in 74.3% of the patients with whole anterior segment irradiation and in 19.2% with sector-based irradiation. Patients with sector-based PBT had a stable visual acuity of logMAR 0.1, while it declined from logMAR 0.1 to 0.4 after whole anterior segment irradiation. CONCLUSION: We found a significant reduction in radiation-induced secondary glaucoma and glaucoma-associated surgical interventions and stable visual acuity after sector-based irradiation compared with whole anterior segment irradiation. Sector-based irradiation revealed a higher risk for local recurrence, but selected patients with well-circumscribed iris melanoma benefit from applying a lesion-based target volume when treated with sector-based PBT.

UVB promotes the initiation of uveitic inflammatory injury in vivo and is attenuated by UV-blocking protection.

PURPOSE: Uveitic inflammatory injury can cause irreversible visual loss; however, no single animal model recapitulates all the characteristics of human uveitis. Ultraviolet radiation (UVR) is one of the risk factors for uveitis, but the role of UVR in the pathogenesis of uveitic injury is unclear. The aim of this study was to elucidate whether UVB promotes the initiation of, and subsequently contributes to, uveitic inflammatory injury. METHODS: Mice were assigned to either a blank control group or one of three UVB treatment groups: no protection, protection with Nelfilcon A contact lens (Food and Drug Administration [FDA] class II, about 46.8% UVB transmittance), or protection with Etafilcon A contact lens (FDA class IV, about 0.55% UVB transmittance). The contact lenses acted as blocking barriers against UVR. After the application of UVR, pathologic injuries were determined with slit-lamp microscopy and histologic examination. RESULTS: Compared with the intact status of the controls, the anterior eyes of the UVB groups showed pathologic alterations in physiologic properties and tissue integrity. UVR promoted anterior uveitic inflammatory injury, with expansion of the hyperemic iris vessels, over-production of aqueous humor protein, disruption of the blood-aqueous barrier, and embedding of infiltrative leukocytes inside the iridocorneal angle. However, blockage of UVR in vivo retarded the progression of uveitic inflammatory injury. The highest level of UV protection in the Etafilcon A group resulted in greater inhibition of uveitic inflammatory injury than that in the Nelfilcon A group. CONCLUSIONS: This study demonstrates that UVB initiated and promoted uveitic inflammatory injury. UV protection is needed for the clinical management of anterior uveitis. The Etafilcon A lenses provide better protection of the anterior segment of the eye against UVB damage compared with the Nelfilcon A lenses.

Radiation therapy: anterior segment complications.

The goal of radiotherapy is to produce maximal damage to the tumor yet at the same time produce minimal damage to the surrounding tissues. Here we discuss anterior chamber complications of radiotherapy. These can vary from ocular surface irritation to blindness and can be subdivided into acute (<4 weeks) and chronic (>4 weeks). Prevention and management is also discussed and subdivided by affected tissue.

A modified Hartmann-Shack aberrometer for measuring stray light in the anterior segment of the human eye.

PURPOSE: To examine the use of a modified Hartmann-Shack wave front aberrometer (WASCA; Carl Zeiss Meditec AG, Germany) to measure objective stray light caused by forward light scatter from the anterior segment of the human eye. SETTING: HELIOS Klinikum Erfurt/Institute of Biomedical Engineering and Informatics, Ilmenau University of Technology, Germany. METHOD: Scatter parameters, including the Michelson contrast and cross-sectional area at half height (CAHM) were examined in Hartmann-Shack images from ten subjects with a cataract in one eye and an intraocular lens (IOL) in the other. The parameters were compared between each eye. Light scatter was then measured in 40 healthy subjects (age range, 23-75 years) with spherical ametropia ranging from -0.25 to 0.25 diopters. The subjects were divided into three age groups; 23-35, 36-50, and 51-75 years. Light scatter was also measured using four alternative methods. RESULTS: CAHM and contrast were significantly different between the eyes with the cataract and the IOL (P = 0.007 and P = 0.004, respectively). CAHM (r = 0.557, P < 0.001) and contrast (r = -0.467, P < 0.001) were both significantly correlated with age. There were significant differences in CAHM and contrast between the age groups. CONCLUSION: The modified wave front aberrometer can be used to measure stray light, although its diagnostic sensitivity in individual patients must be improved.

Baerveldt shunts in the treatment of glaucoma secondary to anterior uveal melanoma and proton beam radiotherapy.

INTRODUCTION: Melanoma of the iris and ciliary body may be associated with secondary glaucoma. Treatment with proton beam radiotherapy (PBRT) to the anterior segment can also elevate intraocular pressure (IOP), resulting in uncontrolled glaucoma, often requiring enucleation. This is the first prospective study of Baerveldt aqueous shunts in irradiated eyes with anterior uveal melanoma (AUM; affecting the iris or ciliary body). METHODS: Thirty-one eyes with uncontrolled IOP following anterior segment PBRT treatment for AUM were prospectively recruited to undergo Baerveldt shunt implantation. Postoperative examinations were performed on day 1; weeks 1, 3, 6, 9; months 3, 6, 9, 12 and annually thereafter. Surgical success was defined as IOP 21 mm Hg or less and 20% reduction from baseline. All complications were recorded. RESULTS: Mean follow-up was 15.7 months (SD ± 8.3 months). Mean interval from irradiation to shunt implantation was 2.5 years. Mean preoperative IOP was 31.0 (± 10.3) mm Hg; mean IOP at last visit was 15.0 (± 5.0) mm Hg; mean pre-operative glaucoma medications were 3.3 (± 1.3); postoperatively 0.7 (± 1.3) glaucoma medications. Surgical success rate was 86% using glaucoma medications. Four eyes had minor postoperative complications, none of which were sight threatening. There were no local tumour recurrences or systemic metastases. There were no enucleations caused by ocular hypertension. CONCLUSIONS: Baerveldt shunts were effective in lowering IOP, with few complications, in eyes treated with total anterior segment irradiation for AUM.

Ultraviolet radiation and the anterior eye.

The eye is on the one hand dependent on visible light energy and on the other hand can be damaged by these and the contiguous ultraviolet (UV) and infrared wavelengths. Diseases of the eye in which sunlight has been implicated have been termed the ophthalmohelioses, and these conditions pose a significant problem to the eye health of many communities. The ophthalmohelioses have a tremendous impact on patients' quality of life and have significant implications on the cost of health care. Although cataract is not entirely caused by insolation, it now seems certain that sunlight plays a contributory role-cataract extraction is one of the, if not the most, commonly performed surgical procedures in many societies. Pterygium, typically afflicting a younger population, adds a tremendous burden, both human and financial, in many countries. We review evidence that peripheral light focusing by the anterior eye to the sites of usual locations of pterygium and cataract plays a role in the pathogenesis of these conditions. Recognition of the light pathways involved with foci at stem cell niches has directed our investigations into inflammatory and matrix metalloproteinase-related pathophysiologic mechanisms. An understanding of the intracellular mechanisms involved has provided some insight into how medical treatments have been developed for the effective management of ocular surface squamous neoplasia. The concept of peripheral light focusing has also provided direction in the prevention of these diseases. This has resulted in improved sunglass design and the further development of UV-blocking contact lenses. With the development of ocular UV fluorescence photographic techniques, we have been able to demonstrate preclinical ocular surface evidence of solar damage. Evidence that diet may play a role in the development of certain conditions is reviewed. The conundrum of the public health message about solar exposure is also reviewed, and in this context, the potential role of vitamin D deficiency is summarized. The eye may play a role in the development of individualized assessment techniques of solar damage, perhaps allowing us to provide better advice to both individuals and populations.

Does the eye benefit from wearing ultraviolet-blocking contact lenses?

OBJECTIVES: The human eye is exposed to toxic ultraviolet radiation (UVR) from sunlight and artificial sources. The UVR-induced damage occurs in ocular tissues from the corneal surface to the retina. Although the cornea and crystalline lens provide inherent UVR protection, the anterior ocular surface and the limbus, which contains stem cells, receive toxic levels of UVR from relatively short solar exposures. METHODS: Shading headwear and some UVR-blocking sunglasses are designed to reduce direct solar exposure but may not protect the eye from diffuse ambient and surface reflected light. If the squint mechanism is reduced because of the reduction of visible light, the ocular surface is then exposed to ambient and reflected UVR. In addition, laterally incident radiation that is focused across the cornea onto the limbus, a phenomenon known as peripheral light focusing, can increase the dose at the nasal limbus by a factor of 20. RESULTS: The UVR-blocking contact lenses that cover the limbus provide protection from all sources of ocularly incident UVR. Although directly relating solar UVR dose to ocular damage is epidemiologically challenging, irradiation of ocular cell cultures can estimate the toxic effects of UVR exposure. The use of UVR-blocking contact lenses greatly increases the time the wearer can be exposed to solar UVR before a toxic ocular dose is reached. CONCLUSIONS: There is a need for the development of a scientifically rigorous, clinically applicable ocular protection factor metric, based not only on the transmittance of eyewear but on the protection afforded from the total UVR field and the length of that exposure.

Ultraviolet absorption by contact lenses and the significance on the ocular anterior segment.

It is well established that both acute and chronic ultraviolet (UV) exposure can lead to various ophthalmic pathologic conditions in the anterior segment. Several scientific studies have demonstrated that after UV exposure, the unprotected cornea is vulnerable to damage in the epithelial, stromal, and endothelial cellular layers. DNA damage, apoptosis, and altered protease expression are all examples of harmful changes that can occur within the cornea after irradiation. Beyond the cornea, damage associated with UV exposure, such as decreased antioxidant levels and increased reactive oxygen species production, has been noted in the aqueous humor and crystalline lens. Ultraviolet-blocking contact lenses have the potential to provide protection against such exposure to harmful UV radiation. Experimental use of UV-absorbing contact lenses prevented detrimental cellular changes to the cornea and maintained corneal clarity after UV exposure. Additionally, studies suggest that shielding the aqueous humor and crystalline lens from irradiation with UV-absorbing contact lenses aids in protection against precataractous changes. Despite ongoing research, to date, neither chronic nor clinical studies have been performed in humans to demonstrate that wearing UV-blocking contact lenses reduces the risk of developing cataracts or other ocular disorders within the anterior segment. This article will discuss the impact of UV exposure on ocular tissue and the need for adequate UV protection, with particular emphasis on UV-blocking contact lenses.

Prevention of UV-induced damage to the anterior segment using class I UV-absorbing hydrogel contact lenses.

PURPOSE: To determine whether class I ultraviolet (UV) light-blocking contact lenses prevent UV-induced pathologic changes in a rabbit model. METHODS: Twelve rabbits were assigned to 1 of 3 treatment groups (n = 4), as follows: senofilcon A (class I UV blocking) contact lenses; lotrafilcon A contact lenses (no reported UV blocking); no contact lens. The contralateral eye was patched without a contact lens. Animals received UV-B (1.667 J/cm(2)) exposure daily for 5 days. Postmortem tissue was examined as follows: in the cornea, the expression of matrix-metalloproteinases (MMPs) was evaluated by zymography, and apoptosis was evaluated by TUNEL and caspase-3 ELISA; ascorbate in the aqueous humor was evaluated by nuclear magnetic resonance spectroscopy; crystalline lens apoptosis was evaluated by TUNEL and caspase-3 ELISA. RESULTS: Exposed corneas showed a significant increase in MMP-2 and -9, TUNEL-positive cells, and caspase-3 activity in the lotrafilcon A group compared with the senofilcon A group (all P = 0.03). A significant decrease in aqueous humor ascorbate was observed in the exposed lotrafilcon A lens-wearing group compared with the exposed senofilcon A lens-wearing group (P = 0.03). Exposed crystalline lenses had significantly increased caspase-3 activity in the lotrafilcon A group compared with the senofilcon A group (P = 0.03). Increased numbers of TUNEL-positive cells were noted in both the lotrafilcon A and the non-contact lens groups. CONCLUSIONS: The authors show that senofilcon A class I UV-blocking contact lenses are capable of protecting the cornea, aqueous humor, and crystalline lens of rabbits from UV-induced pathologic changes.

A clinical assessment of the anterior eye in arc welders.

BACKGROUND: Corneal irradiation with high doses of ultraviolet-B (UVB) has been shown to damage the corneal endothelium in animals. Human occupational exposure to ultraviolet radiation (UVR) in welding is considered a risk for endothelial damage but the evidence for such an effect is limited. METHODS: External eye photographs and non-contact specular micrographs (Topcon SP2000-P) were obtained from 102 white males aged between 32 and 62 years, 51 being arc welders (with 24 +/- 7 years experience) and 51 office workers. Most welders reported repeated occupational exposure to UVR (that is, welder's 'flashes'). RESULTS: Welders reported a higher level of ocular symptoms and a higher prevalence of pingueculae (47 versus 12 per cent), but only one case with pterygium. The average endothelial cell areas were the same in welders and office workers (398 +/- 55 microm(2) versus 400 +/- 56 microm(2); p = 0.868) as were the endothelial cell density (ECD) values (2,555 +/- 342 cells/mm(2) versus 2,541 +/- 308 cells/mm(2); p = 0.825). ECD decreased with years of welding experience (p < 0.01) but not faster than the decrease in ECD due to age. CONCLUSIONS: Repeated occupational ultraviolet radiation exposure through welding is not associated with any obvious differences in the corneal endothelium. No differences were observed in either ECD or cell polymegethism. Despite the periodic welding flashes, the exposure levels are below those needed to cause damage to the corneal endothelium.

Evaluation of treatment by pulsed electromagnetic fields in a rabbit hyphema model.

PURPOSE: Previous clinical studies have suggested a positive effect of low-frequency pulsed electromagnetic fields (PEMF) on wound healing and inflammation in the eye. We tried to test the value of PEMF treatment in a hyphema animal model with well-defined conditions. METHODS: After injection of citrated autologous blood for the production of hyphema, 16 rabbit eyes were treated with 10 or 20 mT for 60 min on 4 days within the postoperative week. Two control groups with hyphema alone (n = 8) and PEMF irradiation without hyphema (n = 4) were also included. The rate of resorption was recorded daily. Histopathologic evaluation was performed. RESULTS: The incidence of endothelial cell damage and fibrotic clots was markedly reduced in the 10-mT group while the resorption time of 8 days was identical with the control group. In the 20-mT group, the complication rate and the resorption time was increased versus the control group. CONCLUSIONS: The use of PEMF treatment is of some, however, limited value as it did not reduce the resorption time of hyphema but displayed a dose-dependent, beneficial influence on some serious side effects. Future clinical studies with low-dose PEMF irradiation are justified and should determine the optimal dosage and suitable indications of PEMFs as an adjunctive treatment in ocular inflammation or trauma.

Flicker parameters are different for suppression of myopia and hyperopia.

Axial eye growth rates in the chicken are controlled by local retinal image-processing circuits. These circuits quantify the loss of contrast for different spatial frequencies and promote axial eye growth rates in correlation with the amount of retinal image degradation ("deprivation myopia"). They also distinguish whether the plane of focus lies in front of or behind the retina. How the sign of defocus is detected still remains unclear. Cues from chromatic aberration are not important. In an attempt to isolate retinal circuits controlling the development of myopia or hyperopia, young chickens were raised in flickering light of different frequencies (12 and 6 Hz) and duty cycles (4-75%) produced by rotating chopper disks. The effects of flickering light on refractive errors and change in axial growth rates induced by translucent occluders or defocusing lenses were measured by infrared retinoscopy and A-scan ultrasound, respectively. Retinal electrical activity was evaluated by flicker ERG after matching flicker parameters and stimulation brightness at retinal surface. Changes in retinal and vitreal dopamine content caused by flicker in occluded and normal eyes were determined by HPLC-ECD. Strikingly, suppression of myopia occurred for similar flicker parameters, whether induced by translucent occluders ("deprivation") or negative lenses ("defocus"). The degree to which myopia was suppressed was correlated with the duration of flicker dark phase and with the ERG amplitude. In contrast, suppression of hyperopia did not correlate with these parameters. We conclude that two different retinal circuits with different temporal characteristics are involved in the processing of hyperopic defocus/deprivation and of myopic defocus, the first one dependent on flicker ERG amplitude. However, we did not find any correlation between the rate of dopamine release and the degree of inhibition of deprivation myopia in flickering light.

Transscleral ciliary body photodynamic therapy using phthalocyanine and a diode laser: functional and morphologic implications in albino rabbits.

BACKGROUND AND OBJECTIVES: To evaluate the morphologic and functional effects of ciliary body photodynamic therapy (PDT) using phthalocyanine and a diode laser. MATERIALS AND METHODS: The upper half of the left eye ciliary body of 16 albino rabbits was irradiated transsclerally using a 670-nm diode laser (400 mW/cm2) after intravenous injection of phthalocyanine (6 mg/kg). The animals were observed for a maximum of 2 months by means of tonometry, biomicroscopy, and fundus examination. At the end of the follow-up period, they were killed and their eyes were prepared for light and electron microscopy. RESULTS: Transscleral PDT resulted in intraocular pressure (IOP) reduction in the treated eye, which lasted about 2 weeks. During this time, the treated eye had IOP values that were significantly lower than its baseline IOP values and the IOP values of the untreated eye (P < .05). One month after the procedure, the IOP had returned to baseline values. Histologic examination revealed vascular endothelial cell damage causing vascular thrombosis in the treated areas. The architecture of the two ciliary epithelium layers showed a significant abnormality. Disappearance of epithelial apical junction complexes and loss of the normal b-cytomembrane enfolding were observed in the course of electron microscopic examination. Large intercellular spaces between epithelial cells were noticed. All of these changes had subsided by the end of the second postoperative month. CONCLUSION: Transscleral phthalocyanine-mediated PDT with the parameters used in this experiment results in significant but temporary functional and morphologic alterations in the ciliary bodies of albino rabbits.

Irritation of the anterior segment of the eye by ultraviolet radiation: influence of nerve blockade and calcium antagonists.

The aim of this investigation was to determine the influence on anterior segment inflammation elicited by UV radiation, of ocular denervation and pharmacological blockade of sensory nerve fibers with capsaicin, tetrodotoxin and calcium antagonists. Both eyes of pigmented rabbits were exposed for 5 min to UV radiation (254 nm); 24 h later, inflammatory signs were evaluated by biomicroscopy of the corneal epithelium, the stroma and the endothelium and scored from 0 to 4. Conjunctival vasodilation and miosis were also assessed. Two weeks before UV exposure, a group of rabbits received a retrobulbar injection of ethanol or of 1% capsaicin. Intact, capsaicin-treated and alcohol-denervated animals were treated topically, prior to UV exposure, with tetrodotoxin (0.78 mM) and the calcium antagonists diltiazem (1-28 mM) and nifedipine (10 mM). UV radiation produced at 24 h signs of corneal irritation, conjunctival hyperemia, miosis and elevated protein content of the aqueous humor. Retrobulbar injection of 99% alcohol or 1% capsaicin did not diminish significantly the inflammation of tissues directly exposed to UV radiation, although extension of inflammatory signs to unaffected areas was prevented. Pre-treatment of normal and denervated eyes with diltiazem attenuated UV-induced eye irritation signs at concentrations of 10 mM or over. The effect was less pronounced with tetrodotoxin and was not obtained with nifedipine. These findings suggest that the contribution of a neurogenic mechanism to anterior segment inflammation induced by UV exposure is modest. They also show that high concentrations of diltiazem, but not of nifedipine, effectively reduced inflammation of the anterior segment of the eye evoked by UV radiation.(ABSTRACT TRUNCATED AT 250 WORDS)

The appearance of active plasminogen activator of urokinase type (u-PA) in the rabbit anterior eye segment irradiated by UVB rays. A histochemical and biochemical study.

Repeated irradiation of the rabbit eye with UV rays of 312 nm wavelength (UVB) evoked the appearance of active plasminogen activator of urokinase type (u-PA) in the anterior eye segment. Using histochemistry, active u-PA appeared first in the corneal epithelium followed by the corneal endothelium, inflammatory cells in the corneal stroma and the lens epithelium. With a semiquantitative fluorescent method active u-PA was also found in the tear fluid and aqueous humour. UV rays of 365 nm wavelength (UVA) under the same conditions did not cause the appearance of active u-PA in the anterior eye segment.

Use of non-subjective analysis of lens transparency in experimental radiation cataract research.

Historically the major impediment to radiation cataract follow-up has been the necessarily subjective nature of assessing the degree of lens transparency. This has spurred the development of instruments which produce video images amenable to digital analysis. One such system, the Zeiss Scheimpflug slit lamp measuring system (SLC), was incorporated into our ongoing studies of radiation cataractogenesis. It was found that the Zeiss SLC measuring system has high resolution and permits the acquisition of reproducible images of the anterior segment of the eye. Our results, based on about 650 images of lenses followed over a period of 91 weeks of radiation cataract development, showed that the changes in the light scatter of the lens correlated well with conventional assessment of radiation cataracts with the added advantages of objectivity, permanent and transportable records and linearity as cataracts become more severe. This continuous data acquisition, commencing with cataract onset, can proceed through more advanced stages. The SLC exhibits much greater sensitivity reflected in a continuously progressive severity thereby avoiding the artifactual plateaus in staging which occur using conventional scoring methods.

The damaging effect of UV rays (with the wavelength shorter than 320 nm) on the rabbit anterior eye segment. I. Early changes and their prevention by catalase-aprotinin application.

In experiments carried out in rabbit eyes, UV rays of 254 or 312 nm wavelength damaged the anterior eye segment, whereas those of 365 nm wavelength did not. Two min irradiation with 254 nm UV rays led to a decrease of catalase activity in the corneal epithelium. After 5 min irradiation the catalase activity in the epithelium was not detectable at all. Catalase activity was also diminished in the corneal endothelium and lens epithelium. In this stage the changes were accompanied by decreased activities of Na(+)--K(+)-dependent adenosine triphosphatase, gamma-glutamyl transpeptidase and increased activities of lysosomal enzymes in the corneal and lens epithelium as well as in the corneal endothelium. The transparency of the cornea and lens was decreased. Plasmin activity appeared in the tear fluid. The irradiation with UV rays of 312 nm caused similar disturbances, however, a longer exposure was necessary. In contrast, irradiation with UV rays of 365 nm did not produce any changes. The described corneal disturbances were prevented by dropping of catalase solution on the eye surface during the irradiation or shortly after it. However, after a protracted irradiation aprotinin had to be added to catalase to achieve the healing. The decrease of catalase activity and its prevention by a local application of catalase suggests a key role of oxyradicals in the damage of the eye by UV rays.

Histopathologic findings in large uveal melanomas after brachytherapy with iodine 125 ophthalmic plaques.

Eyes of 25 patients among a series of 100 consecutive patients who underwent iodine 125 brachytherapy for extremely large uveal melanomas measuring more than 7-8 mm in height had to be enucleated after an average interval of 1.4 years. The dose delivered to the tumor apex was 120-150 Gy. Indications for enucleation were most frequently radiation-induced alterations in the anterior segment with loss of fundus visibility. Eight cases showed insufficient tumor regression, and two cases were suspicious for growth. Microscopically complete tumor necrosis was found in ten eyes. Six cases were classified as "uncertain tumor regression." Apparently "viable" tumor cells were seen in nine eyes. This group of eyes showed a significantly shorter interval between therapy and enucleation. One specimen showed extraocular tumor extension. Brachytherapy with iodine 125 may result in complete tumor necrosis, even in large uveal melanomas. The morphologic extent of tumor necrosis seems to be positively correlated with the interval after therapy.