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Ocular morbidity after radiotherapy of orbital and conjunctival lymphoma

February 1987
Eye (London, England) 1 ( Pt 1)(1):90-6

February 1987
1 ( Pt 1)(1):90-6

DOI:10.1038/eye.1987.14

Source
PubMed

Authors:

Eric Michael Bessell

Nottingham University Hospitals NHS Trust

Rodger A.F. Whitelocke

The Royal Marsden NHS Foundation Trust

One hundred and fifteen patients were treated for lymphoma of the conjunctiva and orbit between 1970 and 1984. One hundred and twelve patients received radiotherapy to the orbit, of whom 73 (65 per cent) had at least one year of follow-up by an ophthalmic surgeon. Patients with low-grade lymphomas (97) mostly received 30 Gy in 15 fractions to the orbit over a period of 3 weeks. Those with high-grade lymphomas (18) mostly received 40 Gy in 20 fractions over 4 weeks. Most were treated using anterior and lateral radiation fields to the orbit with shielding of the cornea and lens. This technique delivered a mean lens dose of 15 Gy. The early and late ocular and orbital morbidity in these patients was low. Eight radiation-induced cataracts developed of which only six interfered with vision. None has needed cataract surgery. No patients developed radiation retinopathy and only 5 had disorders of ocular lubrication.

Distribution of radiation dose fo r treatment of the right orbit with 60 Co y-rays when anterior lens shielding is not used.

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Histogram of distribution of radiation dose to the germinative zone of the lens when anterior lens shielding is used. Five radiation induced cataracts were observed when lens shielding was used and these occurred at doses to the germinative zone of 15 Gy (3 lenses) and 18 Gy and 24 Gy (J lens each).

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Graph of reduction in visual acuity attributa ble to radiation induced cataract. Circles = shielded lenses Squares = unshielded lenses In one case, where the lens received 30 Gy, subsequent fo llow-up was at another centre. A radiation-induced cataract with slight reduction in vision was observed, but accurate visual acuity measurements were not obtained before death.

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Life-table estimate of probability of cataract

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Figures - uploaded by Eric Michael Bessell

Content may be subject to copyright.

Content uploaded by Eric Michael Bessell

Content may be subject to copyright.



Ocular Morbidity After Radiotherapy of Orbital and

Conjunctival Lymphoma

          





        

           

               

         

  

           



             



    

         

         



   

       

      

       

    

    

      

        



     

     



       



     



       

  



        

     

      

  



      





 





 







     

    





 

     

   





 

 



    



 

     

     

      





        





     

 



    



    

      



 

    



     



       

       

      



 

        

      











      

     

  

       

 

       

        

     

  



       

       





    

    

      

       

 

        

 

 



  

    

 



    

   

        







         

       



      



   

     

       



 





      

  

  

     

      





 

       



      



 

      

       

       

   

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 

 

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 





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









 

  





   



        







 

      

   

       

      

    

        







 

      







    

      

      







       



      

     

     



      

  

     

  

   

     



 

 

    

   

   

    

    

   

  

      

 

 

 

 

 

 



 

 





       



     

     







        

        







  





   











 





   



       





      

     









 

      



 



 









    

 



   

       



 

    



  



  

       

    



     



    





     





     





       





 

      

    

 

 



 



 

    

    

                

               

                 

     





     

     

  

    

 



 















      

 



    





      





 

   



   

   

 

    

 

  

  

 

 

 



      

    

  

 

 

  

       

       

      



        



     

       





    









   







      

    





      

     

    

  

   



   





      









        





      







      

     

       

    

   

  

  





   



  

      



 

   







     







  

 















    

 







 

 

    

       









    

       

   

 

       

      

    



   

    

       

     

 

     



    





    

    

     

     

    

   





       

     







     

      



         





   



    

    









 















      





       

     











         

   

   

 

 

  



    

    

 

    

       

        

    

       

  



       

    

 

       

      

     

 



     

    



     



      

     

       

   



       



    

     

 

A Clinical Study of Intensity-Modulated Radiotherapy-Induced Dry Eye Disease in Head and Neck Malignancies

Article

Dec 2022

Context: Dry Eye Disease is a multifaceted disorder caused by a variety of factors ranging from age to demographic profile. Radiation-induced dry eye disease is a relatively unexplored domain of this disease. Aim: To explore the various factors contributing to dry eye disease in patients receiving radiation therapy for head and neck malignancies with a fixed dose and duration of radiotherapy. Settings and design: A cross-sectional study conducted at a tertiary healthcare centre during a period of 1 year. Method and material: The study included 101 patients with head and neck malignancies who received a 60-Gray (Gy) dose of radiotherapy over a duration of 30 weeks. Patients were evaluated for signs and symptoms of dry eye on day 30 after completing their radiotherapy cycles using slit lamp biomicroscopy and various other tests for dry eye and compared with age, gender, location of malignancy, and adjunctive chemotherapy. Results: Out of a total of 101 patients, 45% had mild dry eye disease. 44–45% of mild dry eye disease was seen in the age groups of 20–50 and 51–80 years. The incidence of mild-to-moderate dry eye disease was almost similar (47% and 50 %) in both genders. The incidence of severe dry eye was seen in only 1% of patients. Dry eye disease was more severe in malignancies located closer to the orbit. The use of cisplatin as an adjunctive chemotherapy agent proved to be a risk factor for dry eye disease. Conclusion: Intensity-modulated radiotherapy is not enough to prevent the development of dry eye disease. A close and strict follow-up with an opthalmologist is essential for its prevention and early management.

A Clinical Study of Intensity-Modulated Radiotherapy-Induced Dry Eye Disease in Head and Neck Malignancies

Article

Full-text available

Jan 2022

Dry eye disease in head and neck cancer patients undergoing radiotherapy

Article

Full-text available

Apr 2023
Indian J Ophthalmol

Purpose: To study the incidence of dry eye disease (DED) in head and neck cancer (HNC) patients undergoing external beam radiotherapy (EBRT), to find a correlation between tumor location and total radiation dose with DED, and to report various radiotherapy (RT) induced acute toxic effects on ocular and adnexal structures. Methods: A prospective cohort study was conducted at a tertiary eye-care center on 90 patients of HNC undergoing EBRT from March 2021 to May 2022. All underwent a thorough clinical history and complete ophthalmological examination including an ocular surface disease index (OSDI) questionnaire, visual acuity, anterior segment, angle and posterior segment examination, dry eye workup including the Schirmer test, tear meniscus height, tear break-up time, corneal fluorescein staining and grading, and meibography by auto-refractometer and its scoring at each visit. Patients were evaluated before the start of RT and then at 1 week, 4 weeks, and 12 weeks post-RT. Radiation records of all patients were noted. Data were analyzed using percentage and Microsoft Excel. Results: Of the 90 patients, 66 were male and 24 female (M: F ratio of 2.75) with a median age of 52.5 years (range 24 to 80 years). The most common HNC was the carcinoma oral cavity and lip. Most patients received a total radiation dose between 46 to 55 Gy. DED developed in 48 (53.3%) patients. The incidence of DED increased with the increase in total radiation dose (r = 0.987). DED was also found to be correlated with tumor location (r = 0.983). Conclusion: The incidence of DED positively correlated with the total radiation dose and tumor location.

Modulation of Decellularized Lacrimal Gland Hydrogel Biodegradation by Genipin Crosslinking

Article

Full-text available

May 2024

Purpose: Hydrogels derived from decellularized tissues are promising biomaterials in tissue engineering, but their rapid biodegradation can hinder in vitro cultivation. This study aimed to retard biodegradation of a hydrogel derived from porcine decellularized lacrimal glands (dLG-HG) by crosslinking with genipin to increase the mechanical stability without affecting the function and viability of lacrimal gland (LG)-associated cells. Methods: The effect of different genipin concentrations on dLG-HG stiffness was measured rheologically. Cell-dependent biodegradation was quantified over 10 days, and the impact on matrix metalloproteinase (MMP) activity was quantified by gelatin and collagen zymography. The viability of LG epithelial cells (EpCs), mesenchymal stem cells (MSCs), and endothelial cells (ECs) cultured on genipin-crosslinked dLG-HG was assessed after 10 days, and EpC secretory activity was analyzed by β-hexosaminidase assay. Results: The 0.5-mM genipin increased the stiffness of dLG-HG by about 46%, and concentrations > 0.25 mM caused delayed cell-dependent biodegradation and reduced MMP activity. The viability of EpCs, MSCs, and ECs was not affected by genipin concentrations of up to 0.5 mM after 10 days. Moreover, up to 0.5-mM genipin did not negatively affect EpC secretory activity compared to control groups. Conclusions: A concentration of 0.5-mM genipin increased dLG-HG stiffness, and 0.25-mM genipin was sufficient to prevent MMP-dependent degradation. Importantly, concentrations of up to 0.5-mM genipin did not compromise the viability of LG-associated cells or the secretory activity of EpCs. Thus, crosslinking with genipin improves the properties of dLG-HG for use as a substrate in LG tissue engineering.

Enhancement of lacrimal gland cell function by decellularized lacrimal gland derived hydrogel

Article

Full-text available

Feb 2024

Sustainable treatment of aqueous deficient dry eye (ADDE) represents an unmet medical need and therefore requires new curative and regenerative approaches based on appropriate in vitro models. die Verringerung Tissue specific hydrogels retain the individual biochemical composition of the extracellular matrix and thus promote the inherent cell´s physiological function. Hence, we created a decellularized lacrimal gland (LG) hydrogel (dLG-HG) meeting the requirements for a bioink as the basis of a LG model with potential for in vitro ADDE studies. Varying hydrolysis durations were compared to obtain dLG-HG with best possible physical and ultrastructural properties while preserving of the original biochemical composition. A particular focus was placed on dLG-HG´s impact on viability and functionality of LG associated cell types with relevance for a future in vitro model in comparison to the unspecific single component hydrogel collagen type-I (Col) and the common cell culture substrate Matrigel. Proliferation of LG epithelial cells (EpC), LG mesenchymal stem cells, and endothelial cells cultured on dLG-HG was enhanced compared to culture on Matrigel. Most importantly with respect to a functional in vitro model, the secretion capacity of EpC cultured on dLG-HG was higher than that of EpC cultured on Col or Matrigel. In addition to these promising cell related properties, a rapid MMP-dependent biodegradation was observed, which on the one hand suggests a lively cell-matrix interaction, but on the other hand seriously limits the cultivation period. Concluding, dLG-HG possesses decisive properties for the tissue engineering of a LG in vitro model such as cytocompatibility and promotion of secretion, making it superior to unspecific cell culture substrates. However, deceleration of biodegradation should be addressed in future experiments.

The Impact of Robotic Fractionated Radiotherapy for Benign Tumors of Parasellar Region on the Eye Structure and Function

Article

Full-text available

Jan 2023

Purpose: To evaluate the radiation effect of fractionated robotic radiotherapy of benign tumors located in the parasellar region on the anterior and posterior segments of the eye. Methods: A prospective observational study based on the expanded ophthalmological examination. The pre-treatment baseline was used as a control for the post-radiotherapy follow-up examinations. The study group consists of 34 patients (68 eyes) irradiated using the CyberKnife system. There were ten patients with cavernous sinus meningioma, nine with pituitary adenoma, five with meningioma of the anterior and middle cranial fossa, five with meningioma in the region close to optic chiasm, three with craniopharyngioma, and two with meningioma of the orbit. All patients were treated using three fractions of 600-800 cGy. We assessed the impact of radiation on the eye based on changes in anatomical and functional features. The condition of the eye surface, central corneal thickness (CCT), endothelial cell density (ECD), lens densitometry, central macular thickness (CMT), and retinal nerve fiber layer (RNFL) were the anatomical features assessed. The functional tests were best-corrected visual acuity (BCVA), intraocular pressure (IOP), visual field (VF) and visual-evoked potentials (VEP). An ophthalmologic examination was performed before and 6, 12, 18, and 24 months after radiotherapy. Results: We did not observe any significant changes in BCVA, IOP, CCT, CMT, VF, and VEP, nor in the slit-lamp examination during the two-years observation. We found a significant decrease in ECD at all follow-up measurements. The drop in ECD exceeded approximated age-related physiological loss. The reduction in ECD was not large enough to disrupt corneal function and thus affect vision. We also observed a statistically significant reduction of RNFL in all observation time points. However, there was no correlation between the dose delivered to the optic pathway and the decrease in RNFL thickness. The thinning of the RNFL was not significant enough to impair visual function. Conclusion: Fractionated robotic radiotherapy of the tumors located close to the optical pathway is safe and does not impair patient's vision. Minor changes found in optic nerve anatomy (RNFL thinning) might be related to radiation effect or tumor compression. The causal relation between low doses of radiation delivered to the cornea and the observed significant but slight decrease in ECD is uncertain. The observed changes did not cause visual disturbances perceivable by the patients.

Radiation Therapy: Conjunctival and Eyelid Tumors

Chapter

Mar 2019

Radiation therapy is most often administered as an adjunctive treatment for lesions with high-risk features, such as nodal metastases, perineural invasion, and aggressive histologic subtype, or as salvage therapy for residual or recurrent disease after surgery. Definitive radiation therapy is a standard for management of conjunctival lymphoma and an option for cutaneous basal or squamous cell cancers when the disease is locally advanced and resection would be excessively morbid. Treatment may be delivered via external beam radiation therapy (EBRT), which includes traditional megavoltage photons, proton therapy, orthovoltage X-rays, and electron beam therapy, or via brachytherapy, using handheld applicators, surface plaques, or interstitial seeds. Single or multi-fraction regimens may be selected. Radiation-induced morbidity is influenced by total and daily dose of radiation therapy, as well as irradiated volume. Various techniques exist to reduce dose to nearby organs at risk. For the treatment of large or locally invasive tumors, expected cosmesis after radiation therapy may be poor.

Primary radiation therapy in stage I/II indolent orbital lymphoma – a comprehensive retrospective recurrence and toxicity analysis

Article

Full-text available

Mar 2022
EUR J HAEMATOL

Purpose or Objective To provide a comprehensive recurrence and toxicity analysis of patients treated with radiotherapy alone for stage I/II (Ann‐Arbor classification) indolent orbital lymphoma. Material and Methods We retrospectively reviewed the medical charts of 46 patients (and 51 orbits) treated at our centre with radiotherapy between 1995 and 2012 for biopsy‐proven stage I/IIE primary orbital lymphomas. We evaluated treatment response and performed a comprehensive toxicity analysis with correlation to delivered radiation dose. Results At diagnosis, the median age was 63.5 years (range: 20–92). At initial diagnosis 43 and 3 patients had unilateral, synchronous bilateral involvement while there were 2 cases of contralateral metachronous failure. The predominant histological subtype was extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue in 42 (91.3%), follicular in 1 (2.2%), lymphoplasmacytic lymphoma in 1 (2.2%) and other indolent histology in 2 (4.3%) patients. Most lymphomas were located in the conjunctiva (18/35.3%) or eyelids (18/35.3%). Thirty‐eight (82.6%) patients presented with stage I while 8/46 (17.4%) with stage II disease. The median radiation dose was 39.6 Gy (range: 21.6–48.6 Gy) delivered in 1.8–2 Gy single fractions. At a median follow‐up of 83 months (range: 7–258 months), the complete remission rate was 98%. A local relapse was observed in 2/51 (3.9%) orbits and 4/46 (8.7%) patients had systemic relapse. The 5‐ and 10‐year PFS rates were 79.2% (95% CI: 73.0%–85.4%) and 67.6% (95% CI: 59.4%–75.8%); 5‐ and 10‐year OS was 83.6% (95% CI: 77.9%–89.3%) and 76.5% (95% CI: 69.4%–83.6%), respectively. In total, 66 acute toxicity events (all‐grade) were observed: 5/51 (9.8%) ≥G2 acute conjunctivitis, 2/51 (3.9%) cases of G2 acute keratitis, 1/51 (2%) cases of ≥G2 ophthalmagia and 12/51 (23.5%) cases of ≥G2 xerophthalmia. Furthermore, 45 chronic adverse events were observed in 34/51 (66.7%) irradiated orbits with 30 late adverse events attributed to cataract. Conclusion Our analysis confirms the role of radiotherapy alone at lower doses in the treatment of indolent orbital lymphomas. Further research is required to assess the efficacy of ultra‐low‐dose radiotherapy and anti‐CD20 monoclonal antibodies to further mitigate long‐term sequelae.

Organs at risk radiation dose constraints

Article

Full-text available

Dec 2021
CANCER RADIOTHER

Dose constraints are essential for performing dosimetry, especially for intensity modulation and for radiotherapy under stereotaxic conditions. We present the update of the recommendations of the French society of oncological radiotherapy for the use of these doses in classical current practice but also for reirradiation.

Radiation retinopathy intricacies and advances in management

Article

Dec 2021

Background: Radiation retinopathy is a chronic, progressive, vision-threatening complication from exposure to various radiation sources. While several treatment modalities are available, proper management for this disease is a continuing challenge with no consensus on the most efficacious. Objective: The aim of this article is to provide an updated review of the published literature on the course of the disease, available treatments and their efficacies, frequency of regimen, core issues in patient management, and additional newer treatment modalities, including possible prophylactic approaches. Value: We also highlighted the challenges encountered with managing chronically treated patients through an analysis of a clinical case report on a patient who was treated for several years with different modalities after a diagnosis of radiation retinopathy.

Postradiation retinopathy. A fluorescence fundus angiographic study

Article

Nov 1970

Sohan Singh Hayreh

Post-radiation retinopathy. A fluorescence fundus angiographic study

Article

Nov 1970

S S Hayreh

Lymphocytic tumours of indeterminate nature: A 5-year follow-up of 98 conjunctival and orbital lesions

Article

Jul 1978

Ninety-eight adnexal lymphocytic tumours of indeterminate nature have been followed up for at least 5 years. Both non-disseminating and disseminating tumours have either very similar or identical histopathological features. It is not possible to make a definitive diagnosis when the lesions are first seen, and a conclusion can be reached only after a prolonged follow-up. The nature of the non-disseminating tumours is unknown.

Visual Results and Ocular Complications Following Radiotherapy for Retinoblastoma

Article

Nov 1978
ARCH OPHTHALMOL-CHIC

Between 1956 and 1974, 28 children with retinoblastoma have been irradiated with the linear accelerator at the Stanford University Medical Center. Twenty-seven children (96%) have been cured of their tumor, with follow-up ranging from 2 1/2 to 21 years. In these survivors, 50 eyes were affected. Twelve were treated by primary enucleation and 38 were irradiated. Sixteen of the 38 irradiated eyes (42%) were ultimately enucleated for recurrent tumor, neovascular glaucoma, or inability to observe the tumor through opaque media. Thus, 22 (58%) irradiated eyes were saved. Of these, five eyes had visual acuity of 20/40 or better, five had 20/50 to 20/100, nine had 20/200 to hand motion, and three had light perception or no light perception. Radiation therapy can sterilize the tumor and maintain useful vision in many children with retinoblastoma.

Effects of Irradiation on the Eye 1

Article

Oct 1976

From 1954 through 1971, 47 patients with malignant tumors of the nasal cavity and paranasal sinuses were treated with an entire eye included in the tumor dose volume. All patients were treated with megavoltage radiation and received approximately 6,000 rads in 30 fractions in six 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 (5-FU) was used in conjunction with high-dose radiotherapy, loss of vision was much more frequent and all patients had either visual loss or major clinical difficulties.

Effects of fast neutrons on the eye

Article

May 1976

The study of 93 eyes receiving neutron irradiation establishes the character of the ophthalmic complications of neutron. Significant changes are produced in the eyelids, conjunctiva, and cornea, but the production of cataract is relatively unimportant. No reaction was seen after neutron treatment that had not already been seen after chi or gamma radiation. That the unavoidable damage is similar to that reported with other forms of radiation, and not worse, is an important finding in view of the statistically significant benefit of neutron treatment to patients in a controlled clinical trial of advanced tumours of the head and neck (Catterall and others, 1975). The observations indicate that the improved cure rates with neutrons are not obtained at the expense of inflicting greater damage to normal structures. This investigation has also shown that the neutron effects of treating these very extensive tumours are acceptable and that, with carefully measured doses, they are predictable. The dose-response relationship in categories of clinical effect for a smaller series of patients, reported in Table 1 of our preliminary communication (Brown and other, 1976), is confirmed.

Report of the Committee on Hodgkin's Disease Staging

Article

Dec 1971

Cataracts after total body irradiation and marrow transplantation: A sparing effect of dose fractionation

Article

Aug 1984
INT J RADIAT ONCOL

We examined 277 patients, who have been followed for 1 to 12 years after marrow transplantation, for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, usually cyclophosphamide 50 mg/kg X 4 intravenously, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing 60Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients), usually at increments of 2 to 2.25 Gy/day for 6 to 7 days for cumulative doses of 12 to 15.75 Gy. To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, and 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only (p less than 0.00005), suggesting a significant sparing effect with use of TBI dose fractionation. Addition significant risk factors included the chronic use of steroids posttransplant (highly associated with the presence of chronic graft-versus-host disease), and the diagnoses of acute lymphoblastic or chronic myelogenous leukemia.

The effects of irradiation on the eye and optic nerve

Article

Jun 1983
INT J RADIAT ONCOL

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.

Experimental radiation cataract—Its clinical relevance

Article

Jun 1983
Bull New York Acad Med

Radiation cataract, a type of complicated cataract, has proved a useful model for studying the mechanisms involved in the development of senile opacities. The initial insult is to the lens epithelium with subsequent disorganization of the meridional rows and the appearance of the abnormal nucleated fibers (Wedl) cells) posteriorly. Experimental studies involved in the formation of our present understanding of cataract development are detailed. Much remains to be done but it would appear that the opacification process is primarily the result of basic changes in the epithelial cells.

Ocular morbidity after radiotherapy of orbital and conjunctival lymphoma

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