|Ahead of print publication
Radiation-induced neovascular glaucoma: A devastating disease
Megha Gopalakrishna, Kavitha Srinivasan, Venkatesh Rengaraj
Department of Glaucoma, Aravind Eye Hospital, Puducherry, India
|Date of Submission||27-Dec-2018|
|Date of Acceptance||09-Jun-2019|
|Date of Web Publication||06-Feb-2020|
Glaucoma Services, Aravind Eye Hospital, Thavalakuppam, Puducherry - 605 007
Source of Support: None, Conflict of Interest: None
Neovascular glaucoma (NVG) is a potentially blinding form of secondary glaucoma, with radiation being one of the rare causes. This report is aimed to discuss a case of NVG caused secondary to radiotherapy (RT) given for a nasal malignancy. A 50-year-old male presented with enophthalmos, dry eye, and NVG 3 years after receiving RT for chondrosarcoma of nasal and paranasal cavities. He was given topical antiglaucoma medications, retinal laser, and intravitreal bevacizumab injection and thus prevented the eye from becoming a painful blind eye. The radiation oncologist and ear, nose, and throat specialists have to liaise closely with ophthalmologist when patients receive radiation involving the eye in the treatment field to prevent, diagnose, and treat this devastating condition.
Keywords: Neovascular glaucoma, ophthalmic complications of radiotherapy, radiation
| > Introduction|| |
Neovascular glaucoma (NVG) is a serious complication of brachytherapy and external beam radiotherapy (RT) was given for ophthalmic tumors. Cataract, glaucoma, vitreous hemorrhage, and radiation retinopathy are a few of the common complications of RT. However, there are not many reports emphasizing the importance of ophthalmic evaluation following RT in non-ophthalmic head-and-neck tumors. In this report, we shall be describing about NVG secondary to RT which was given for malignancy of the nasal cavity and paranasal sinuses.
| > Case Report|| |
A 50-year-old-male presented to us with complaints of irritation and burning sensation in both eyes for 3 years and sudden diminution of vision and pain in the right eye (RE) for 20 days. He had visited a nearby ophthalmologist for the same complaints, for which he was started on antiglaucoma medications such as brinzolamide, brimonidine, and timolol drops and acetazolamide tablets. His reports revealed that he had undergone right medial maxillectomy and lacrimal sac marsupialization for chondrosarcoma of the nasal cavity and paranasal sinuses 3 years ago and external beam RT for 2 months following surgery. Total dose of 66 Grey (Gy) to residual disease and 60 Gy to clinical target volume in 33 fractions were delivered by image-guided radiation therapy technique over 2 months. He is a known diabetic and on treatment for 6 years.
On examination, the best-corrected visual acuity was 6/12 in the RE and 6/9 in the left eye (LE). He had mild enophthalmos, periorbital fat atrophy, bony defect in the right orbital floor, few hypopigmented patches over the skin, and ectropion of lower lid in the RE [Figure 1]. Anterior segment evaluation using a slit-lamp biomicroscopy revealed circumcorneal congestion, severe dry eye, anterior chamber inflammation, neovascularization of the iris (NVI), and posterior chamber intraocular lens in the RE [Figure 2]. He had mild dry eye and immature cataract in the LE. The intraocular pressure (IOP) measured by applanation tonometry was high in the RE in spite of antiglaucoma medications and measured 36 mm of Hg (normal range: 10–21 mm of mercury). However, it was normal in the LE and measured 21 mm of Hg. Visualization of the anterior chamber angle by gonioscopy showed open angles with few synechiae but no neovascularization of angle in the RE and open angles in the LE.
|Figure 1: Photograph of the right eye showing sunken eyes (enophthalmos), periorbital fat atrophy (white arrow), pigmentary changes over skin (purple arrow), and congestion (yellow arrow)|
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|Figure 2: Anterior segment photograph of the right eye showing neovascularization of the iris (blue arrow), ectropion uveae, and posterior chamber intraocular lens|
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Fundus showed pallor of the optic nerve head with a relatively increased optic cup-to-disc ratio (CDR) of 0.65, with very few retinal superficial hemorrhages and soft exudates in all quadrants in the RE most likely suggesting radiation retinopathy [Figure 3]. He had a CDR of 0.6 and normal background retina in the LE [Figure 4]. He was started on tear substitutes for dry eyes in both eyes. Anti-inflammatory drop was started in the RE. The antiglaucoma medications were continued to control the IOP. He was given intravitreal injection of bevacizumab which is an anti-vascular endothelial growth factor (VEGF) the very next day. He was given retinal laser, the panretinal photocoagulation (PRP) in three sittings, to ablate the ischemic retina. The first sitting was given on the same day and the next two sittings in the consecutive week.
|Figure 3: Fundus photo of the right eye showing pale retina and soft exudates (red arrow) and few hemorrhages|
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On follow-up after 2 days of presentation, the dry eye had reduced and NVI was regressing [Figure 5]. IOP was reduced to 27 and 11 mmHg in the RE and LE, respectively. On subsequent follow-up visits, the eye was stabilizing, but the IOP continued to be on the higher side. He underwent diode cyclophotocoagulation inferior 180° to reduce IOP. On his last visit a few months back, the eye stabilized, the antiglaucoma therapy was shifted to two drugs, brimonidine and timolol, and anti-inflammatory drop was tapered and stopped. The tear substitutes were continued.
|Figure 5: Anterior segment photo of the right eye postretinal laser and antivascular endothelial growth factor injection showing regressed neovascularization (blue arrow) and atrophic iris patches|
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| > Discussion|| |
NVG is a potentially blinding form of secondary glaucoma characterized by proliferation of fibrovascular tissue in the iris and the anterior chamber angle. However, the timely presentation of our patient, an accurate diagnosis, and prompt initiation of treatment have prevented the eye from becoming a painful blind eye. If at all a patient complaints of redness, pain, irritation, or watering in the eye following radiation, an ophthalmological evaluation is a must. The cause may be the more common dry eye or a sight-threatening disease such as NVG.
NVG is associated with a wide range of conditions causing retinal ischemia, with diabetic retinopathy and retinal vein occlusions being the front runners. Radiation is one of the rare causes, at the bottom of the list.
On exposure to suprathreshold doses of irradiation, retinal vascular endothelial cells are effected which leads to retinal hypoxia and release of VEGFs, resulting in neovascularization and radiation retinopathy., The VEGF thus released moves anteriorly in search of normal capillaries, leading to neovascularization of the iris and the angle. Hence, it is a posterior segment insult which manifests anteriorly. Initially, the angles are open with just raised pressures. Gradually, the new vessels become more widespread with an overlying fibrovascular membrane resulting in eventual total synechial closure of the angle. This progression can take place in just matter of days to weeks. However, the chance of developing NVG without frank radiation retinopathy with neovascularization of retina as in our case is poorly defined.
Radiation retinopathy can present between 7 months and 8.5 years after external beam radiation. Total dose, fraction size, and number of fractions all are key determinants in the development of radiation retinopathy. The probability of retinopathy increases steeply above 50 Gy. Our patient had received a total of 66 Gy to the residual disease. It usually does not occur in total doses <45 Gy unless associated with comorbidities such as diabetes. Our patient, being a diabetic, might have added to the insult. However, most of the literature describes retinopathy and NVG caused due to radiation given to ophthalmic tumors. Non-ophthalmic head-and-neck tumors treated with radiation where the eyes are less protected have also to be kept in mind. The presence of complications such as enophthalmos, skin changes, and dry eye confirms radiation to be the reason.
Anti-VEGF has been studied and found effective for radiation retinopathy. It is also useful in preventing and treating secondary neovascularization in eyes with uveal melanoma since there is a higher concentration of VEGF in eyes treated with RT. Reports have been published on the successful treatment of nonneoplastic NVG with bevacizumab., PRP is another modality of treatment with good success rates. Our patient responded favorably to a single injection of intravitreal bevacizumab and PRP.
Therefore, a trial of anti-VEGF therapy and PRP would be effective in radiation-induced NVG even if the retina shows no signs of neovascularization. Prospective studies are necessary to evaluate the long-term efficacy of anti-VEGF therapy and PRP in such a setting.
| > Conclusion|| |
NVG can develop as a delayed effect of radiation even after 3 years. There need not be extensive retinal ischemia for NVG to develop. It is really important to examine the patient as a whole and to look for orbital and various facial changes to clinch the diagnosis. The patients receiving head-and-neck radiation should be informed of these possibilities and advised to consult an ophthalmologist if any of the symptoms are present. Hence, it is important that the radiation oncologist and ear, nose and throat specialists liaise closely with ophthalmologist when patients receive radiation involving the eye in the treatment field.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Finger PT, Kurli M. Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol 2005;89:730-8.
Wand M. Neovascular glaucoma. In: Ritch R, Shields MB, Krupin T, editor. The Glaucomas-Clinical Science. 2nd
ed., Ch. 51. St. Louis: Mosby; 1996. p. 1073-129.
Archer DB, Amoaku WM, Gardiner TA. Radiation retinopathy – Clinical, histopathological, ultrastructural and experimental correlations. Eye (Lond) 1991;5(Pt 2):239-51.
Archer DB. Radiation Retinopathy. In Ophthalmology, 3rd
ed. Vol. 6. Yanoff M, Duker JS. Mosby Elsevier Philadelphia; 2009. p. 636-9.
Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ. Radiation retinopathy. Ophthalmology 1982;89:1494-501.
Parsons JT, Bova FJ, Fitzgerald CR, Mendenhall WM, Million RR. Radiation retinopathy after external-beam irradiation: Analysis of time-dose factors. Int J Radiat Oncol Biol Phys 1994;30:765-73.
Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys 2008;70:974-7.
Missotten GS, Notting IC, Schlingemann RO, Zijlmans HJ, Lau C, Eilers PH, et al.
Vascular endothelial growth factor a in eyes with uveal melanoma. Arch Ophthalmol 2006;124:1428-34.
Iliev ME, Domig D, Wolf-Schnurrbursch U, Wolf S, Sarra GM. Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma. Am J Ophthalmol 2006;142:1054-6.
Davidorf FH, Mouser JG, Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina 2006;26:354-6.
Kinyoun JL, Lawrence BS, Barlow WE. Proliferative radiation retinopathy. Arch Ophthalmol 1996;114:1097-100.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]