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Year : 1991  |  Volume : 39  |  Issue : 1  |  Page : 2-5

Role of radiation therapy in the treatment of benign ocular diseases

1 Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India
2 Department of Radiation Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India

Correspondence Address:
Room No. 111, Laxmi Hostel, R.P.C. II, All India Institute of Medical Sciences. Ansari Nagar,New Delhi -110029
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Source of Support: None, Conflict of Interest: None

PMID: 1894338

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Radiation therapy, although a prime treatment modality for malignant disease, has few definitive indications for some benign ocular diseases too. Orbital pseudotumour, Graves ophthalmopathy and pterygium are the conditions where the radiation oncologist has got an important role to play. This article reviews the current status of the role of radiation and its effectiveness in the management of these diseases.

How to cite this article:
Racheline, Paul V K, Ganesh T, Sharma S, Singal S, Joshi R C. Role of radiation therapy in the treatment of benign ocular diseases. Indian J Ophthalmol 1991;39:2-5

How to cite this URL:
Racheline, Paul V K, Ganesh T, Sharma S, Singal S, Joshi R C. Role of radiation therapy in the treatment of benign ocular diseases. Indian J Ophthalmol [serial online] 1991 [cited 2020 Apr 6];39:2-5. Available from: http://www.ijo.in/text.asp?1991/39/1/2/24490

  Introduction Top

The prime concern of the radiation oncologist is the treatment of patients with malignant tumours. With the recognition of the potential risks of all ionizing radiation such as late skin injury, carcinogenesis, leukeamogenesis and genetic damage, radiation treat­ment of benign diseases, once common, now forms a very small fraction of the radiation oncologist's practice. In ocular practice, however, there are definite indications for such treatment. Radiation therapy continues to be the accepted treatment for those benign disease that do not respond to other modalities of therapy. The benefits of radiation therapy generally greatly outweigh the risks, which are frequently minimal [1],[2] Recent advances in ultrasound and computerised tomography (CT) have permitted localization of orbital lesions and sophisti­cated high energy irradiation techniques facilitate im­proved dose distribution without significant damage to the normal tissues.

This article analyses the present status of radiation therapy in the management of benign ocular diseases. The indications, techniques and effectiveness are evaluated along with a brief review of the pertinent literature.

  Orbital pseudotumour Top

Orbital pseudotumour, sometimes are described as idiopathic orbital inflammation, non specific granuloma of the orbit, ect the term is used to describe a non specific inflammatory lesions of the orbit presenting as a space occupying lesion which clinically may simulate a neoplasm. By definition, the term excludes lesions with an identifiable etiology such as bacterial, fungal or parasitic infections or foreign body reactions. They also exclude orbital inflammatory lesion associated with sys­temic disorders such as Grave's disease, Reidel's struma, Wegner's granulomatosis, sarcoidosis, ect [3],[4]

  Pseudotumours Top

Orbital pseudotumours may be unilateral or bilateral and may vary in size and location. Extensive lymphocytic infiltration produces inflammatory signs, periorbital swelling, decreased ocular motility and pain. Anteriorly situated lesions may present with palpable masses whereas retrobulbar lesions usually produce proptosis with progressive loss of vision. Orbital pseudotumour is confused most commonly with Grave's ophthal­mopathy [3]. CT with its characteristic features is helpful in distinguishing pseudotumour from Grave's disease [5],[6] where the retroocular muscles are primarily involved and which generally is bilateral. But biopsy is usually required, especially in cases with unilateral disease, to rule out lymphoma or metastatic carcinoma. Quite often, the patients are misdiagnosed as having Grave's oph­thalmopathy or orbital lymphoma [3][7],[8] The information gained from the CT assists the ophthalmologist in plan­ning the optimal place for biopsy and the radiation therapist in outlining the treatment fields.

A variety of methods have been employed to treat orbital pseudotumour. Surgical excision may be employed to remove accessible, localized lesions but recurrence is common [4]. Furthermore, excision may be difficult be­cause of the location and/or accessibility of the lesions and this mode of therapy is not appropriate in case with diffuse involvement [9]. High dose glucocorticosteroid therapy has resulted in regression of both focal and diffuse lesions, although not invariably [9],[10]. Relapses are common when this therapy is tapered or discon­tinued and the side effects of corticosteroid treatment may be frequent and highly undesirable Spontaneous remissions sometimes occur without any therapy at all [9],[11].

Radiotherapy, on the other hand, produces dramatic and rapid improvement in signs and symptoms, the response continues for up to 6 months following radia­tion and regression obtained is generally long lasting. Only modest doses are required and with the modern megavoltage radiation, complications of treatment are negligible. Therefore, orbital radiotherapy, is a preferable alternative to surgical or corticosteroid treat­ment for pseudotumour [3],[7],[10],[12],[13]

Henderson has proposed a histologic classification in which the pseudotumour lesions are termed Type-I or Type-II [4]. Type-I is rare and is characterized by necrotiz­ing vasculitis with perivascular inflammatory infiltrates and varying degrees of fibrosis. The more common Type-II is characterized by a uniform polymorphous infiltrate of mature small lymphocytes and plasma cells with scattered large lymphocytes, without any formation of lymphoid follicles or granuloma. Type-II pseudo­tumours are more radiosensitive than Type-I [3].

A 4-6 MV photon beam is generally used, with unilateral or bilateral temporal fields posterior to the lens. Doses in the range of 1500-2000 cGy in 2 weeks general suffice for achieving a long term regression [3],[7],[12],[13] Treatment individualization coupled with meticulous treatment planning using simulator, CT and com­puterized treatment planning allows the dose to the lens to be kept below 100 cGy in 2 weeks which is well within normal tissue tolerance and is not associated with an v significant risk of cataract development [14]. Donaldson [3] has used split beam technique for better lens protection and has reported excellent results.


Exophthalmos in patients with Grave's disease due to a progressive, bilateral, chronic inflammatory reaction in the orbital tissue, particularly the extraocular muscles, with lymphocytic infiltration and edema. An interplay of delayed hypersensitivity reaction and autoimmunity is thought to be the possible etiologic factor [15],[16] and the fundamental pathologic., process is thought to represent a cellular immune reaction in extraocular muscles. Near­ly 90% of the cases have associated 'hyperthyroid ism but it may occur even in the absence of detectable thyroid disease. The eye' disease tends not to be in­fluenced by the treatment of the hyperthyroid condition. The ocular symptoms may prove very distressing and require treatment. The diagnosis is essentially clinical based upon the demonstration of characteristic eye signs but recently ultrasonography [17] and CT scan [6] have added significantly to the diagnostic accuracy by demonstrating the characteristic increased bulk of the extraocular muscles. These are especially useful and indicated in euthyroid individuals. CT also aids in dif­ferentiating this condition from that with bilateral pseu­dotumour of the orbit [5],[6]

Since in most case, the ophthalmopathy is uninfluenced by the treatment of thyroid disease, a host of modalities have been tried in an attempt to achieve long term regression. None of them has proved to be the ideal treatment. A variety of immunosuppressive therapies li­ke steroids [18],[19],[20],plasma heresies [21],[22] azathiopri­ne [23],[24] cyclophosphamide [25]and cyclosporin-A [20].[26],sub [ 27] sub have been tried. But these must be given for long periods of time, are associated with major side effects and are not always effectivel6. Surgical orbital decompression has also been attempted but results are not encouraging [28] .

Since lymphocytes are especially radiosensitive, radia­tion therapy directed at the posterior orbit would be a logical method of treatment and should provide quick and long lasting remissions [16]. Anatomic, physiologic and immunologic -concepts concerning the pathogenesis of eye lesions constitute the rationale behind its employment. Excellent to good response in 80% of the cases occurring shortly after the treatment is very well documented [15][16],[29],[30] Best results are ob­tained when there is optic nerve involvement and visual loss, with little change in proptosis and extraocular muscle symptoms [16]. A favourable response is observed even in those individuals who had previously responded poorly to systemic corticosteroid therapy [15]. A long dura­tion of symptoms prior to therapy is generally associated with a poor response to radiation 15 but this observation has been challenged recently [29].

Small bilateral orbital fields are used, to treat both the orbits posterior to the lens, employing megavoltage radiation. Lead shielding, a well collimated beam and a slight posterior angulation (5-10°) are used to protect the lens. A midplane dose of 15.20 Gy in 10 fractions over 2 weeks is generally sufficient [15],[16] but special care need to be exercised in selection of beams and calculation of doses to avoid excessive doses to the pituitary, hypothalamus and the anterior segment of the globe. The therapy is generally safe and no major immediate or delayed complications have been reported [15],[16]

  Pterygium Top

Pterygium is a triangular wing shaped fibrovascular proliferation of bulbar conjunctiva, with the base towards the palpebral angle and the rounded apex towards the cornea. As it advances, the apex passes between the corneal epithelium and the basement membrane which ultimately is damaged leading to permanent corneal scarring. The patient seeks treatment because of visual and cosmetic problems. In considering the efficacy of any therapeutic procedure, one has to consider the post treatment recurrence rate, complications of treatment and the ultimate cosmetic outcome.

Surgical ablation in toto is essential, irrespective of whether the lesion is primary or recurrent after previous treatment. Though histologically it is benign, simple surgical removal without any further therapy is as­sociated with a high recurrence rate or 20-30% [32],[33] This is because most of the times, complete removal is impossible or is damaging, thus making the recurrence inevitable. Hence a host of modalities have been tried in an attempt to reduce the recurrence rate. These include carbolization [31], mucosal transplantation [31], lamellar cor­neal grafting [31]sub , antimitotic agents like thio-TEPA [32],[33],[34]sub mitomycin [31],[35] and steroids [33]. But none of these methods has proved to be uniformly successful and recurrence rates are quite high.

Prophylactic post operative beta irradiation has consis­tently been shown to be efficient in reducing the potential for regrowth, as evidenced by low recurrence rates (%) reported after its use in numerous series [31],[34],[[36],[37],[38],[39],[40],.[41] It gives excellent cosmetic results in more than 95% of patients with minimal associated complica­tions [36],[39],42,43 Long term follow up studies show that the primary treatment is successful in 90% of the patients and 80% of the failures can still be salvaged by a second course [36],[38]

A recurrent pterygium almost always recurs if treated by the same surgical method [38] and each successive recur­rence becomes a greater test of the ophthalmologist's surgical skill, a grave threat to the patient's vision and much more difficult to control [40]. Post operative radiation because of its simplicity, minimum morbidity, excellent cosmetic results and good cure rates is the primary treatment nowadays. The treatment is delivered by an ophthalmic applicator of 90 Strontium, a fission product of 235 Uranium. It has got a half life of 28 years and emits beta rays of energy range 0.5Mev to 2.27MeV having a half value thickness in the tissues of 1.5mm.

The anterior surface of the lens situated at a distance of 4 mm from the mid surface of the cornea receives 4% of the dose and the retina situated at 25 mm receives 0.3%40. It is applied directly on the bare area of the sclera after instillation of local anaesthetic. The use of adjacent fields to cover the entire area may sometimes be necessary

Good surgical technique, precise radiation calibration and calculation and proper post operative and post radiation care are very important in reducing the recur­rence and complication rates. Causes of failure include inadequate surgery, Suboptimal radiation therapy, large size requiring piecemeal radiation leading to a probable geographic miss and delay after surgery of more than 48 hours in instituting the radiation therapy36,39. Effect of previous treatment on the outcome of radiation therapy remains controversial [36],[39] The interval be­tween treatment and recurrence is considerably variable and is a persuasive argument for long term follow up. 50% of the recurrences occur after 1 year and 25% after 2 years. Retreatment of failures by another course of combined therapy is by no means futile [36],[38] and can be done by the same method [40]. But a third course of combined treatment is generally not recommended [36]sub Thio-TEPA [36] and topical cortisone= [40] have been found to be of some use in such patients.

Fibroblast cells which are actively and directly respon­sible for recurrence are physiologically and radiobiologi­cally more prone to radiation damage during the peak mitotic activity which increases significantly a few hours after operation in the surgical bed and reach a peak in a few days. The therapy to be effective should be delivered as early after surgery as possible, preferably within 12-48 hours [37],[39][40]

Post operative beta radiation is generally an effective and safe therapy, provided the calibration, calculation and the technique is proper [36],42 The commonly practiced dose schedules are 300 reps in 3 fractions over 3 weeks [36],[39] 2500 reps in 2 fractions over 2 weeks [34] and 1800-2200 reps delivered in a single fraction [40]. All are equally effective, with a recurrence rate of 1.5-4.0% but fractionation is preferable due to less complications and better cosmesis. Changes ranging from acute inflamma­tion to cataract formation can occur but are usually not seen. Although cellular changes are demonstrable in a majority of patients, no serious sequelae follow 42.

  References Top

Rockville, M.D., A review of the use of ionizing radiation for the treatment of benign disease. Vol.1, pp 1-2, U.S. Department of Health, Education and Welfare, Bureau of Radiological Health, 1977.  Back to cited text no. 1
Kopicky, J., Order S.E., Survey and analysis of radiation therapy of benign diseases. Vol.11 Appendix B, pp 13-442. U.S. Department of Health, Education and Welfare, Bureau of Radiological Health, 1977.  Back to cited text no. 2
Donaldson. S.S. McDougall, I.R., Egbert, P.R., Enzmann. D.R. Kriss, J.P., Treatment of orbital pseudotumour by radiation therapy. Int. J. Radiat. Oncol. Biol. Phys., 6:79-86, 1980.  Back to cited text no. 3
Henderson, J.W., Inflammatory pseudotumour and orbital sarcoid. In Or­bitalTumours, chap. 19, pp 555-588. Philadelphia, W.B. Saunders, 1973.  Back to cited text no. 4
Enzmann, D., Donaldson, S.S. Marshall, W.H.. Kriss, J.P., Computed tomography in orbital pseudotumour (idiopathic orbital inflammation). Radiology, 120:597-601, 1976.  Back to cited text no. 5
Enzmann, D, Marshall, W.H., Rosenthal, A.R., Kriss, J.P., Computed tomography in Grave's ophthalmopathy. Radiology, 118 : 615-620, 1976.  Back to cited text no. 6
Fitzpatrick, P.J.. Macko, S., Lymphoreticular tumours of the orbit. Int. J. Radiat. Oncol. Biol. Phys., 10:333-340, 1984.  Back to cited text no. 7
Knowles, D.M., Jakobiec, F.A., Orbital lymphoid neoplasms. Cancer. 46: 576-589. 1980.  Back to cited text no. 8
Heersink, B., Rodrigues, M.R., Elanagan, J.C., Inflammatory pseudo­tumour of the orbit. Ann. Ophthalmol., 9 : 17.29, 1977.  Back to cited text no. 9
Jellinek, E.H., The orbital pseudotumour syndrome and its differentiation from endocrine exophthalmos. Brain, 92 : 35-58, 1960.  Back to cited text no. 10
Chavis, P.M., Garner, A., Wright, J.E., Inflammatory orbital pseudotumour : A clinicopathological study. Arch. Ophthalmol.. 96:1817-1822, 1978.  Back to cited text no. 11
Rao, D.V., Cosby, K., Smith, M., Lymphomas and pseudolymphomas of the orbit (abstr). Int. J. Radiat. Oncol. Biol. Phys., 8(Suppl.l) : 114, 1982.  Back to cited text no. 12
Kim, R.Y., Roth, R.E., Radiotherapy of orbital pseudotumour. Radiology. 127: 507-509, 1978.  Back to cited text no. 13
Hall, E.J., Radiation cataractogenesis. In Radiologyfor the Radiologist. pp. 243-249, Maryland, Harper and Row, 1973.  Back to cited text no. 14
Donaldson, S.S., Bagshaw. M.S., Kriss, J.P., Supervoltage orbital radiotherapy for Grave's ophthalmopathy. J. Clin. Endocrinol. Metab., 37 276-285, 1973.  Back to cited text no. 15
Ravin. J.G., Sisson, J.C., Knapp, W.T., Orbital radiation for the ocular changes of Grave's disease. Am.J. Ophthalmol., 79 : 285-288, 1975.  Back to cited text no. 16
Coleman. D.J. Reliability of ocular and orbital diagnosis with B-scan ultrasound. Am.J. Ophthalmol., 74: 704-718, 1972.  Back to cited text no. 17
Brown, J., Coburn, J.W. Wigod, R.A., Hiss, J.M., Dowling, J.T., Adrenal Steroid therapy of severe infiltrative ophthalmopathy of Grave's disease Am.J. Med., 34: 786-795, 1963.  Back to cited text no. 18
Werner, S.C., Prednisone in the emergency treatment of malignant exoph­thalmos. Lancet, 1 : 1004-1006, 1966.  Back to cited text no. 19
Kahaly, G., Cyclosporin and prednisone vs. prednisone in treatment of Grave's ophthalmopathy : a controlled, randomized, clinical study. Eur. J. Clin. Invest., 16 : 415-422, 1986.  Back to cited text no. 20
Dandona, P., Marshall, N.J., Bidey, S.P., Nathan, A.W., Havard, C.W.H., Successful treatment of exophthalmos and pretibial myxoedema with plasmapheresis. Brit. Med. J., 2 : 667-671, 1979.  Back to cited text no. 21
Glioner, D., Sand, G., Hoyoux, P., Mahieu, P., Winard, R., Beneficial effects of intensive plasma exchange therapy in severe Grave's ophthalmopathy. Acta Endocrinol., 111: 30-38, 1986.  Back to cited text no. 22
Burrows, G.N., Mitchell, M.S., Howard, R.O., Morrow, L.B., Immunosup­pressive therapy for the eye changes of Grave's disease. J. Clin. En­docrinol. Metab. 31 : 307-311. 1970.  Back to cited text no. 23
Winand, R., Mahieu, P., Prevention of malignant exophthalmos after treat­ment of thyrotoxicosis. Lancet, 1 : 1196-1201, 1973.  Back to cited text no. 24
Bigos, S.T., Nisula, B.C., Daniels, G.H., Eastman, R.C., Joshston, H.H. Kohler. P.O., Cyclophosphamide in the management of advanced Grave's ophthalmopathy : A preliminary report. Ann. Int. Med., 90:921-923, 1979.  Back to cited text no. 25
Weetman, A.P., McGregor, A,M., Ludgate, M., Lazarus, J.H., Cyclosporin improves Grave's ophthalmopathy. Lancet, 2:486-489, 1983.  Back to cited text no. 26
Utech, C., Wulle, K.G., Bieler, E.U., Pfannenstiel, P. Panitz, N., Kiefer, H., Treatment of severe Grave's ophthalmopathy with cyclosporin A. Acta Endocrinol., 110:493-498, 1985.  Back to cited text no. 27
Garman, C.A., De Santo, L.W., MacCarty, C.S., Riley, F.C., Optic neuropathy of Grave's disease : Treatment by transantrai or transfrontal orbital decompression. N. Eng. J. Med., 290:70-75, 1974.  Back to cited text no. 28
Donaldson, S.S., Kriss, J.P., McDougall, I.R., Bagshaw, M.A., Orbits irradiation in the treatment of Grave's ophthalmopathy - Results in 141 consecutive patients (abstr.) Int. J. Radiat. Oncol. Biol. Phys., 8(suppl.1) 112-113,1982.  Back to cited text no. 29
Bartalena, L., Marocci, C., Chiovato. L.. Laddaga, M., Orbital cobalt irradia­tion combined with systemic steroids for Grave's ophthalmopathy : Com­parison with systemic steroids alone. J. Clin. Endocrinol., 56:1139-1144, 1983.  Back to cited text no. 30
Dash, R.G., Boparai, M.S., Pterygium - Evaluation of management, Ind. J. Ophthalmol., 34: 7-10,1986.  Back to cited text no. 31
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Lentino, W.. Zaret, M.M., Rossignol, B., Ruben feld, S., Treatment of pterygium by surgery followed by beta radiation. Am. J. Roentgenol., 81 : 93-98, 1959.  Back to cited text no. 37
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van den Brenk, H.A.S., Results of prophylactic post operative irradiation in 1300 cases of pterygium. Am.J. Roentgenol., 103, 723-733, 1968.  Back to cited text no. 39
Talbot, A.N., Complication for beta ray treatment of pterygia. Transac. Ophthal. Soc. N.Z. 64 : 496-505, 1985.  Back to cited text no. 40
Tong, E.C.K., Zaret, M.M., Rubenfeld, S.. Cellular changes in the con­junctiva after strontium 90 treatment for pterygium. Am. J. Roentgenol., 106:848-853,1969.  Back to cited text no. 41


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