Constance R. Fitzgerald

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.

The effects of irradiation on the eye and optic nerve

Abstract Late effects of irradiation of the eye and optic nerve in 74 patients are reviewed. Time-dose analyses are performed for lacrimal apparatus, retinal, and optic nerve injuries. Management of radiation complications is discussed. Recommendations are made regarding radiation treatment techniques and methods of reducing the risk of late injury.

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.

Non-Diabetic Retinal Abnormalities in Chronic Pancreatitis

To determine whether retinal abnormalities occur in patients with chronic pancreatitis, ophthalmoscopic and retinal-function evaluation was performed in 28 patients with chronic pancreatitis and 19 healthy subjects. The final threshold of dark adaptation was significantly increased 40 per cent (P less than 0.001) in patients with pancreatitis, whether or not they had steatorrhea. Patients with steatorrhea had a significant decrease of about 42 per cent (P less than 0.001) in the b-wave of the electroretinogram, a measure of both rod and cone function. Seven of the 28 patients complained of difficulty with hight vision; six of these seven had morphologic lesions on ophthalmoscopic examination, confirmed by fluorescein angiography. No correlation was found between any of the retinal abnormalities and the serum vitamin A or zinc levels or glucose tolerance. Non-diabetic retinal lesions and retinal-function abnormalities are common in patients with chronic pancreatitis, even in the absence of steatorrhea.

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 sustained-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.

The Incidence of Retinal Detachment after Penetrating Keratoplasty

Of 610 penetrating keratoplasties reviewed, retinal detachments did not occur after any phakic graft, or after aphakic or combined (keratoplasty and cataract extraction) procedures unless these were associated with vitreous manipulation. A 5.4% incidence of retinal detachment occurred after keratoplasty that involved vitrectomy. The resultant detachments had a poor prognosis probably because of delayd diagnosis and difficulties in visualization. Vitreous manipulation, therefore, may be essential to graft clarity but it is hazardous.

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) ⩽ 150. Seventeen of 21 patients in the malignant group had an interocular L/D difference (L/Dd) ⩾ 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.

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 the 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.

Kinetic Perimetry (in the Plateau Region of the Field) as a Sensitive Indicator of Visual Fatigue or Saturation-Like Defects in Retrobulbar Anomalies

A series of patients with radiation damage has been studied. Retinal vascular changes shown by fluorescein angiography were accompanied by local alterations in the sustained- and transient-like functions. When no retinal manifestations were found, and in all cases where the optic nerve was involved, visual fatigue or saturation-like effects were noted which were revealed as reductions in sensitivity in time. These could be surprisingly subtle. Because of amplification effects, small reductions in sensitivity in time are readily revealed in the plateau region of the central kinetic field. In every instance these effects, once discovered, could be verified using flashing repeat static tests. Comparable results were obtained in all patients tested.