Response of the normal eye to high dose radiotherapy.

Radiation therapy of tumors near the eye or optic nerves often requires incidental irradiation of these structures, even when they are not clinically involved by tumor. Depending on the radiation treatment volume and dose required, radiation injury to the lens, lacrimal apparatus, retina, or optic nerve may result. The time to expression and severity of injury are dose-dependent. This paper reviews the results of 157 patients who were followed for a minimum of 3 years after radiotherapy for primary extracranial tumors at the University of Florida, in which the lacrimal gland, lens, retina, and/or optic nerve(s) received irradiation. This review shows that, after treatment at approximately 1.8 to 2.0 Gy per fraction, the incidence of severe dry-eye syndrome, retinopathy, and optic neuropathy appears to increase steeply after doses of 40, 50, and 60 Gy, respectively.

Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors.

PURPOSE: To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. METHODS AND MATERIALS: Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. RESULTS: Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 and 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of < 59 Gy. Among nerves that received doses of > or = 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic neuropathy after doses of > or = 60 Gy was 11% when treatment was administered in fraction sizes of < 1.9 Gy, compared with 47% when given in fraction sizes of > or = 1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. CONCLUSION: As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced-field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation.

Radiation retinopathy after external-beam irradiation: analysis of time-dose factors.

PURPOSE: To investigate the risk of radiation-induced retinopathy according to total radiation dose and fraction size, based on both retrospective and prospectively collected data. METHODS AND MATERIALS: Between October 1964 and May 1989, 68 retinae in 64 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 26 years; mean, 9 years; median, 8 years). RESULTS: Twenty-seven eyes in 26 patients developed radiation retinopathy resulting in visual acuity of 20/200 or worse. The mean and median times to the onset of symptoms attributable to retinal ischemia were 2.8 and 2.5 years, respectively. Fourteen of the injured eyes developed rubeosis iridis and/or neovascular glaucoma. Radiation retinopathy was not observed at doses below 45 Gy, but increased steadily in incidence at doses > or = 45 Gy. In the range of doses between 45 and 55 Gy, there was an increased risk of injury among patients who received doses per fraction of > or = 1.9 Gy (p = .09). There was also a trend toward increased risk of injury among patients who received chemotherapy (two of two vs. four of ten in the 45-51 Gy range; p = .23). The lowest dose associated with retinopathy was 45 Gy delivered to a diabetic patient by twice-a-day fractionation. The data did not suggest an increased risk of radiation retinopathy with increasing age. CONCLUSION: The current study suggests the importance of total dose as well as dose per fraction, and adds support to a small body of literature suggesting that patients with diabetes mellitus or who receive chemotherapy are at increased risk of injury. A sigmoid dose-response curve is constructed from our current data and data from the literature.

Severe dry-eye syndrome following external beam irradiation.

PURPOSE: There are limited data in the literature on the probability of dry-eye complications according to radiotherapy dose. This study investigates the risk of radiation-induced severe dry-eye syndrome in patients in whom an entire orbit was exposed to fractionated external beam irradiation. METHODS AND MATERIALS: Between October 1964 and May 1989, 33 patients with extracranial head and neck tumors received irradiation of an entire orbit. Most patients were treated with 60Co. The dose to the lacrimal apparatus was calculated at a depth of 1 cm from the anterior skin surface, the approximate depth of the major lacrimal gland. The end point of the study was severe dry-eye syndrome sufficient to produce visual loss secondary to corneal opacification, ulceration, or vascularization. RESULTS: Twenty patients developed severe dry-eye syndrome. All 17 patients who received doses > or = 57 Gy developed severe dry-eye syndrome. Three (19%) of 16 patients who received doses < or = 45 Gy developed severe dry-eye syndrome; injuries in the latter group were much slower to develop (4 to 11 years) than in the higher dose group, in whom corneal vascularization and opacification were usually pronounced within 9-10 months. There were no data for the range of doses between 45.01 and 56.99 Gy. The data did not suggest an increased risk of severe dry-eye syndrome with increasing age. CONCLUSION: Data from the current series and the literature are combined to construct a sigmoid dose response curve. The incidence of injury increases from 0% reported after doses < or = 30 Gy to 100% after doses > or = 57 Gy.

Photoreceptor orientation. A graded disturbance bordering a region of choroidal atrophy.

Retinal photoreceptor orientation was found to be disturbed in the region bordering an area of choroidal atrophy in the eye of a human observer. This disturbance was inferred from the locations of the peaks of psychophysical Stiles-Crawford functions. These peak locations progressively shifted from a normal location near the center of the pupil to well beyond the nasal pupillary margin as the retinal test location approached the visible lesion. We conclude that this disturbance of photoreceptor orientation reflects the operation of tractional forces that interfere with the reorientation of the receptors toward the pupil in a sizable area of the retina surrounding the traction-inducing lesion.

Radiation therapy in and about the retina, optic nerve, and anterior visual pathway. Psychophysical assessment.

Visual changes may develop in patients receiving radiation therapy for malignant neoplasms in and about the optic nerve and anterior visual pathway. Cases have been studied using a series of psychophysical tests, including kinetic perimetry, increment threshold determinations, Flashing Repeat Static Test, and sustained- and transient-like functions. A characteristic time-dependent reduction in sensitivity has been identified in these patients. This finding, in addition to the presence of nerve fiber bundle defects, appears to place the pathologic changes in the axon of the ganglion cell posterior to the lamina cribrosa. Any change in the sustained- and transient-like functions, the organization of which appears to be in the neural retina, was seen only if a concomitant radiation retinopathy was identified.

The use of Healon in a case of rolled-over retina.

A retinal detachment with giant tear and rolled-over retina were repaired using pars plana vitrectomy techniques and intraocular Healon and air injection. Direct manipulation of the retina with instruments was not necessary during the procedure due to the apparent mechanical property of Healon. Although the giant tear was unrolled with Healon injection, revision of the scleral buckle and air injection was needed at a later date to permit final successful reattachment of the retina. The case report presented is intended to provide information concerning the surgeon's technique for the use of Healon in the management of a giant tear with rolled-over retina.

Different functional changes recorded in open angle glaucoma and anterior ischemic optic neuropathy.

The retinal ganglion cell exhibits two types of functional change. The difference in response appears to depend on whether or not the retrobulbar portion of the optic nerve is actively involved. This may imply differences in the myelinated and non-myelinated portions of the optic nerve and associated structures. In open angle glaucoma, alterations in the sustained- and transient-like functions but not in the flashing repeat static test are found. That is, there are changes in spatial neural interactions, but there is no evidence of a visual fatigue or saturation-like effect. In optic nerve radiation damage without evidence of retinal vascular changes, in optic neuritis secondary to multiple sclerosis, chiasmal lesions, and ischemic optic neuropathy (considered here) varying degrees of visual fatigue or saturation-like effects are demonstrated with little or no change in the sustained- or transient-like functions.

The EOG and choroidal malignant melanomas.

Fifty-four patients with a unilateral pigmented choroidal lesion were studied with electrooculography (EOG). Eighteen of 21 patients with histologically proven (13) or presumed (8) malignant tumors of the choroid had light peak-dark trough ratios (L/D) less than or equal to 150. Seventeen of 21 patients in the malignant group had an interocular L/D difference (L/Dd) greater than or equal to 23%, whereas only one of 33 patients with nevi or a condition simulating a nevus had a percent difference of such magnitude. Combining the L/D and L/Dd criteria resulted in a 98% accurate double-blind prediction of the final clinical/pathological results. The EOG is an objective, noninvasive test useful in the diagnosis of choroidal malignant melanomas.

A simple psychophysical technique provides early diagnosis in optic neuritis.

Patients with optic neuritis describe image fading which is particularly evident at bright light levels. The effect is dependent on adaptation level, and high adaptation levels serve as a provocative test. Kinetic and static perimetry and interferometric acuity tests repeated in time reveal this loss in sensitivity. The latter test, using a large field and a high luminance level, is particularly sensitive to both the residua of pathology and very early phases of disease, often before subjective manifestations of anomalies are present. These effects are large in patients with demyelinating diseases. Here, we show that such changes may be revealed in optic neuritis due to other causes as well. Note, the same form of response may be detected in more central lesions, but usually in more circumscribed areas of field.

Transient-like function and associated retinal capillary anomalies. Analysis of a patient with early retinopathy secondary to juvenile-onset diabetes mellitus.

A juvenile diabetes patient exhibiting limited early microvascular changes in the retina has been studied intensively. Like some others showing early signs of diabetic retinopathy, he manifests anomalies in a retinally based transient-like function. At all points tested in this case the sustained-like function was found to be normal. Because his functional and anatomic anomalies are stable and cover a reasonably extensive area of visual field and retina, it is possible to attempt correlative studies with other visual response functions. The transient-like function proves to be a more sensitive indicator of anomaly in this patient than static perimetry or critical flicker frequency.

Anomalous pigment epithelial photoreceptor relationships and receptor orientation.

In order to further investigate the factors influencing retinal receptor orientation, three patients with local disturbances of the receptor/pigment epithelium (PE) interface have been evaluated. Psychophysical and clinical tests have been used to characterize the observed abnormalities. The following conclusions are made. Receptor orientation is lost following a serous detachment of the neurosensory retina and can recover following reattachment of the retina. Orientation may be retained despite the presence of serous detachment of the PE, loss of the light/dark component of the electro-oculogram, and vitelliform-like lesions between the receptors and the PE.

Functional analysis of vision in patients after retinal detachment repair.

A number of tests of vision were performed in patients after surgical repair of retinal detachment. The major tests performed were Snellen visual acuity, interferometric acuity, Stiles-Crawford function, and increment-threshold analysis. In two patients it was possible to evaluate all functions preoperatively. Althrough the sample it modest (ten eyes in nine patients), trends in visual recovery are identified and discussed.

Pars plana vitrectomy for vitreous opacity secondary to presumed toxoplasmosis.

Four patients with vitreous opacity characterized by veil-like membranes with precipitates of presumed inflammatory cells had visual acuities in the affected eye of hand movements only, 20/200, 20/400, and 20/400 over a period of six months or longer. A history compatible with episodes of inflammation secondary to toxoplasmosis and a chorioretinal scar compatible with toxoplasmosis in the involved or opposite eye was present in each patient. Pars plana vitrectomy (with lensectomy in three of the four cases) has afforded information in regard to preoperative and postoperative management of such patients, as well as postoperative results.

Cystoid macular edema as the primary sign of neurosyphilis.

A 34-year-old man had a six-month history of bilateral visual loss that was secondary to cystoid macular edema, which was assumed to be secondary to neurosyphilis on the basis of cerebrospinal fluid serology, cell count, and protein. Good visual acuity was recovered with systemic corticosteroids only after they were used in combination with antitreponemal therapy. This is the first report, to the best of our knowledge, of cystoid macular edema as the primary sign of neurosyphilis documented by fluorescein angiography.

Comparison of visual function studies in two cases of senile macular degeneration.

In this paper two relatively early cases of senile macular degeneration are compared by making use of a number of tests of visual function, some relatively new, coupled with observation of the fundus and analysis by fluorescein angiography. The functional tests include visual acuity, the sustainedlike and transientlike functions which are believed to test inner retinal receptive field properties and to have origin in the inner and outer plexiform layers, the Stiles-Crawford function which reflects the directional sensitivity and orientation of photoreceptors, and increment threshold curves. In one case there was evidence of inner retinal involvement at the time the tests were conducted, but, because the Stiles-Crawford function remained essentially normal, it is assumed that the receptors were not disturbed relative to their orientation. In this case (as in many others), the zone or area exhibiting functional change does not necessarily match the area exhibiting anatomical change as observed by examination of the fundus, fundus photography, and fluorescein angiography. In the second patient there is evidence of both anomalous inner retinal function and disturbance in receptor alignment. The later suggests disorientation of the receptor bed. These findings correlated with the fundus observation and fluorescein angiographic evidence of a leak, resulting in the presence of serous fluid beneath the neurosensory retina. With resolution of this fluid there was a return of the functional tests toward normal. At this time, it is not possible to determine whether, in two cases, the functional changes are proceeding on a parallel course, but are at different stages, or whether they are the expression of somewhat different anomalies.

Retinal receptive field-like properties and Stiles-Crawford effect in a patient with a traumatic choroidal rupture.

Simple psychophysical techniques were used in order to assess layer-by-layer retinal functions in a patient with sub-retinal fluid due to a choroidal rupture following ocular trauma. A substained-like and a transient-like function believed to reflect retinal receptive-field-like properties, and an indicator of retinal receptor orientation (the Stiles-Crawford effect) have been followed in time. Central visual acuity was also measured. Initially all measured functions provided anomalous responses in affected retinal areas. Of interest here is the nature and order of recovery of the measured response functions. Most notable was the rapid rate of recovery of receptor orientation and the slower rate of recovery of the transient-like function.