Effects of irradiation on the eye

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the treatment was changed to combined cytostatic therapy. In addition to high doses (7mg/kg/die) of Prednisolone, ALG and Vinblastin i.v., the patient received perorally Imuran and Leukeran. The doses were determined by the current state of the eye; they were diminished with improvement of the eye. Total healing ensued nine weeks later. In spite of the continued maintaining doses (Prednisolone 0.3mg/kg/die, Leupurin lOOmg/die, Leukeran 2Smg/die, Cuprenil 600mg/die), six weeks later recidivation ensued. Elevation of the dose of the corticosteroid (2mg/kg/die) brought definitive healing. Afterwards the patient received maintaining doses of a cytostatic for six months and local and parenteral corticosteroids for one year. The patient has had total recovery during three years of followup. On the basis of this case, the authors recommend the following combined immunosuppressive therapy. 1. Administration of high doses of corticosteroids 2. Administration of cytostaticas (in case the milder alkylyzing medications are ineffective, the optimal combination is Imuran, Leukeran, and, eventually, Vinblastin) 3. Local and intravenous administration of ALG 4. Administration of Cuprenil (D-Penicillamin) Side effects arising during the treatment consisted of cortisone-diabetes, which was well managed by antidiabetics and which ceased after cortisone therapy was discontinued, and disturbance of the upper respiratory tract, which was resolved by sulfonamid derivatives after completion of ALG therapy. Hematologic changes included no lymphocytes in the peripheral blood from the 4th to 6th week of the combined treatment. In the authors’ opinion, the advantage of their treatment is that, because of the high doses of cytostatics, lower than usual doses of ALG, which in larger amounts often produce severe side effects, can be used. (Abstract by I. Suveges)

Comment I would agree that patients with sympathetic ophthalmia who do not improve with intensive steroid therapy should receive immunosuppressive agents and possibly antilymphocyte globulins. This therapy with immunosuppressive agents and antilymphocyte serum should be handled by someone expert in their administration since these are dangerous agents. The ideal therapy is to treat these patients very energetically at the very earliest stages in order to abort the process and decrease the amount of damage produced. This objective can often be accomplished with corticosteroids alone if they are used in large doses for a short time. T. F. SCHLAEGEL

Effects of Irradiation on the Eye, by R.C. Chan and L.J. Shukovsky. 120:673-675,

Radiology

1976

From 1954 through 197 1,47 patients with malignant tumors of the nasal cavity and paranasal sinuses were treated with the entire eye included in the tumor dose volume. All patients were treated with megavoltage irradiation and received approximately 6000 rad in 30 fractions in 6 weeks. Two-thirds of the patients treated by irradiation alone had no problems with vision or difficulties related to treatment of the eye. When 5-fluorouracil (S-FU) was used in conjunction with high-dose radiotherapy, loss of vision was much more frequent; all patients had either visual loss or major clinical difficulties. Comparison between the patients receiving radiotherapy alone and those receiving radiotherapy plus 5-FU resulted in the following findings: 1. The incidence of total blindness in 3 years for patients receiving radiotherapy and 5-FU was 4 times more frequent than for those who had had radiotherapy alone. 2. In groups receiving radiotherapy with 5-FU, all patients incurred an eye complication or multiple complications or loss of vision within 2 years. 3. Significant cataract formation in those patients treated with 5-FU was far more frequent than in those treated without the drug. 4. In patients who received 5-FU cornea1 lesions often developed, whereas in those with irradiation alone cornea1 lesions of clinical significance developed in only 15%. 5. Chronic conjunctivitis has been the most frequent sequela of radiotherapy without 5-FU, but the incidence levels off after the first year following therapy. The incidence with a chemotherapeutic agent at one year has been 75%, whereas without the drug it has been 25%. (Abstract by R.C. Chan)

Comment Two groups of patients received radiotherapy which includes the eye for malignant tumors of the nasal cavity and paranasal sinuses. Both received 6000 rad; one group received adjunctive intra-arterial 5fluoruoracil. No information is given as to the use of shielding of the anterior segment or the isodose

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curve. Using megavoltage therapy a 6000 rad tumor dose will give a considerably lower dose to the superficial tissues which would include the anterior segment of the eye. There is a dramatic difference in the morbidity and loss of visual function between these two groups. All of the patients treated with fluoruoracil had cornea1 lesions two years after treatment, compared to 10% of those treated with radiotherapy alone. Complete loss of vision was present in 40% of the combined therapy group and only 10% of radiotherapy alone three years following treatment. We can be puzzled by the statistics which show “clinically significant” cataract in 10% of patients with radiotherapy alone and 50% of patients with combined therapy. This implies to me that the isodose curve provided a significantly lower dose to the eye than the tumor dose and there was probably shielding of the anterior segment during therapy. The term “clinically significant” is also misleading. One would expect posterior subcapsular cataracts to be visible in all patients four years after radiotherapy, causing some degradation of visual function. The authors do not state their criteria for “significance.” The absence of the isodose curve or an estimate of ocular dose as well as lack of information about possible shielding makes it difficult to extend their results to more general clinical application. The authors have clearly shown that fluoruoracil potentiates the pathologic effects of radiation upon ocular structure and function. It is less clear in what conditions 75% of patients will retain uncomplicated vision two years following 6000 rad to an orbital tumor. However, the authors’ suggestion that there is unwarranted pessimism about the future of ocular function when the orbit is irradiated is well taken. Their data suggest that with their radiotherapeutic technique this pessimism is unnecessary as two-thirds of the patients seem to do well in the short term. It is to be expected that, if the crystalline lens receives over 200 r in an adult, a significant posterior subcapsular cataract can be expected to develop in 50% of patients within several years. This is a progressive situation as the significance of the cataract as well as the percentage of cases in which it can be recognized will increase with time. STEPHENL. TROKEL

LETTERS To the Editor: The recent excellent review of ocular and orbital phycomycosis by Doctors Schwartz, Donnelly, and 22~3-28, 1977) Klintworth (Surv Ophthalmof noted that approximately 80% of patients with cerebra-rhino-orbital phycomycosis (CROP) have diabetes mellitus. It is worth emphasizing, however, that this disease may be present in a wide variety of clinical settings which have in common the presence of impaired immune defense mechanisms. A recent patient that we saw in consultation demonstrated the importance of suspecting phycomycosis in patients without diabetes mellitus. Case report: This 43-year-old black female was admitted to the University of Illinois Hospital for a cadaver renal transplant. She had a previous history of chronic pyelonephritis and renal failure. The renal transplant was performed but postoperatively she developed acute tubular necrosis and rejection of the transplant. She was treated with high doses of systemic corticosteroids and azathioprine. Hemodialysis and potent antihypertensive agents were necessary. The clinical course was then complicated by gastrointestinal bleeding, leukopenia, thrombocytopenia, and she was treated with multiple broad spectrum antibiotics. Approximately one month following the

renal transplant, she developed a maxilliary sinusitis that was treated with penicillin. The subsequent clinical course was characterized by left periorbital swelling and the development of proptosis, fever, complete ophthalmoplegia, and a central retinal artery occlusion. Because of the absence of diabetes mellitus and only mild, intermittent acidosis related to her renal failure, the diagnosis of phycomycosis was not made. With progression of the patient’s proptosis and sinusitis, debridement of the sinuses was finally performed revealing massive infarction due to phycomycosis. Despite further surgical treatment and intravenous amphotericin B, the patient died. It is of interest that two of the 99 cases reviewed by Schwartz et al. were renal transplant recipients. In the presence of immunosuppression and impaired immune mechanisms, even in the absence of diabetes mellitus, phycomycosis should be suspected in patients with orbital cellulitis, proptosis, or central retinal artery occlusion. Early surgical intervention and aggressive medical management is necessary if the patients are to survive. (Bullock JD, Jampol LM, Fezza AJ: Two cases of orbital phycomycosis with recovery. Am J Ophthalmol 78:81 l-815,

1974). LEE M. JAMPOL,M.D. CHICAGO, ILLINOIS