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Middle East Afr J Ophthalmol. 2013 Jan-Mar; 20(1): 83–86.
PMCID: PMC3617536

Transient Increased Exudation after Photodynamic Therapy of Intraocular Tumors

Abstract

To report transient increased exudation after photodynamic therapy (PDT) of three different intraocular tumors (retinal hemangioblastoma, retinal astrocytoma, amelanotic choroidal melanoma). PDT with verteporfin (6 mg/m2 body surface area) was delivered at a dose of 50 J/cm2 and intensity of 600 mW/cm2 over 83 s. All patients experienced decreased vision within a few days following PDT. Optical coherence tomography showed development of subfoveal fluid in all cases and noncystoid intraretinal edema in the eye with juxtapapillary retinal hemangioblastoma. There was complete absorption of retinal/subretinal fluid with improvement of visual acuity to 20/20 in all cases between 3 weeks to 4 months after PDT.

Keywords: Astrocytoma, Choroidal Melanoma, Complication, Exudation, Eye, Photodynamic Therapy, Retinal Hemangioblastoma, Serous Retinal Detachment, Tumor

INTRODUCTION

Photodynamic therapy (PDT) is based on the interaction of light with a photosensitizer leading to release of cytotoxic singlet oxygen and resultant oxidative damage to the target tissue.1 The tumoricidal activity of PDT is caused by direct cell damage and microvascular injury.24 PDT has been used for the management of various intraocular tumors including circumscribed58 and diffuse choroidal hemangioma,59 choroidal melanoma,1012 retinal hemangioblastoma,1316 retinal vasoproliferative tumor,17,18 and retinal astrocytoma.1921 We describe the development of transient tumor vascular hyperpermeability with increased intraretinal/subretinal fluid following PDT of three different types of intraocular tumors (retinal hemangioblastoma, retinal astrocytoma, amelanotic choroidal melanoma).

Approval was obtained from institutional review board of Wills Eye Institute. Written informed consent was obtained from patients.

CASE REPORTS

Case 1

An asymptomatic 61-year-old female with a 1.5 mm juxtapapillary retinal hemangioblastoma OD showed progressive retinal edema despite three prior off-label intravitreal bevacizumab injections (1.5 mg) [Figures [Figures1a1a and andb].b]. PDT was delivered to the tumor, followed immediately by a fourth intravitreal bevacizumab injection (1.5 mg). One day after the procedure, the patient presented with a complaint of blurred vision. On examination, the best corrected visual acuity (BCVA) had decreased from 20/20 preoperatively to 20/70. Optical coherence tomography (OCT) showed extension of retinal edema into fovea [Figure 1c]. There was spontaneous recovery of BCVA to 20/25 and complete resolution of macular edema 3 weeks after PDT [Figure 1d]. Eight months after PDT BCVA was 20/20 but the patient complained of a persistent paracentral ring of haziness. The tumor remained stable with no recurrent intra- or subretinal fluid during subsequent follow-up of 3 years.

Figure 1
(a) Juxtapapillary retinal hemangioblastoma with adjacent lipid exudation. Note minimal lipid exudation in the papillomacular bundle region (b) Foveal contour is normal before photodynamic theraphy (PDT) (c) OCT performed 1 day after PDT shows retinal ...

Case 2

A 17-year-old female with juxtafoveal retinal astrocytoma OD measuring 6 mm in diameter and 3 mm in thickness underwent successful standard fluence PDT with verteporfin (6 mg/m2; 689 nm diode laser; 600 mW/cm2; 83 s) for management of macular edema originating from the retinal tumor with improvement in BCVA from 20/70 to 20/30. Three years after PDT, BCVA decreased to 20/60 due to recurrent macular edema [Figures [Figures2a2a and andb]b] and she underwent a second standard fluence PDT with verteporfin. Two days after the second PDT, she noted decreased vision. On examination, the BCVA was 20/80 and OCT showed increased subretinal fluid at the fovea [Figure 2c]. Three weeks later BCVA improved to 20/60 and 4 months later best corrected visual acuity was 20/20 with complete resolution of macular edema and subfoveal fluid [Figure 2d]. The patient required two more sessions of PDT during the subsequent 3 years for management of recurrent macular edema.

Figure 2
(a) Partially pigmented retinal astrocytoma (needle biopsy proven) with lipid exudation at the superior, inferior, and nasal margins extending into the fovea, forming a foveal star (b) OCT before PDT reveals moderate intraretinal cystoid edema at the ...

Case 3

A 62-year-old female with visual acuity of 20/20 and an enlarging amelanotic choroidal melanoma in her left eye (OS) measuring 7 mm in basal dimension and 2.7 mm in thickness [Figures [Figures3a3a and andb]b] was treated with PDT. Two days after PDT, the patient noted decreased vision OS and 11 days later, the best corrected visual acuity was measured at 20/200. OCT confirmed subretinal fluid extending from the treated melanoma into the foveal region [Figure 3c]. The vision improved without treatment 1 month after PDTand 3 months later there was complete resolution of subretinal fluid with visual acuity of 20/20 [Figure 3d]. Subsequent tumor growth required treatment with I-125 plaque radiation.

Figure 3
(a) Color fundus photograph showing small amelanotic choroidal melanoma with documented growth (b) OCT shows normal fovea before PDT (c) Eleven days after PDT, neurosensory retinal detachment extending under the fovea is evident (d) Three months after ...

DISCUSSION

Increased exudation has been reported following PDT of ocular conditions other than tumors, including choroidal neovascular membrane (CNVM) and polypoidal choroidal vasculopathy.2225 Reports of increased leakage after PDT from intraocular tumors are limited to juxtapapillary retinal hemangioblastoma.13,16 Possible mechanisms of post-PDT vascular hyper-permeability include direct damage to endothelial cells,26 retinal pigment epithelial damage and dysfunction,27,28 or an angiogenic response induced by PDT.29,30

A post-PDT increase in intraocular tumor leakage is an early phenomenon causing symptoms within a few days of PDT. In all three of our cases, the visual disturbance was transient with complete absorption of fluid and recovery of vision to pre-PDT levels within 1 month after PDT. Despite the transient nature of increased leakage post-PDT, prolonged presence of intraretinal or subretinal fluid or deposition of lipid exudate at the fovea could potentially lead to permanent structural damage and loss of vision. An example is the patient in Case 1 above who noted persistent paracentral field defects up to 8 months after complete absorption of fluid.

The use of off-label intravitreal bevacizumab injection immediately after PDT in our first case did not prevent development of increased retinal edema. It has been shown that increased vascular leakage starts as early as 5-10 min after PDT of rat cremaster muscle.3 Additionally some have proposed that application of anti-VEGF compounds before PDT may be more effective in blocking the effects of VEGF.30 Fingar and co-workers3 also found a direct relationship between dose of photosensitive material used (Photofrin; Pinnacle Biologics Inc., Bannockburn, IL, USA) and the severity of increased vascular leakage and were able to block post-PDT leakage by intra-arterial injection of indomethacin.

In summary, we report development of transient increased leakage causing increased retinal edema or subretinal fluid following PDT for different types of intraocular tumors (retinal hemangioblastoma, retinal astrocytoma, amelanotic choroidal melanoma). Further studies are needed to identify effective methods for prevention of this potentially vision-threatening complication.

Footnotes

Source of Support: Support provided by a donation from Michael, Bruce, and Ellen Ratner, New York, NY 20 (JAS, CLS), the Paul Kayser International Award of Merit in Retina Research, Houston TX (JAS), Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia, PA (CLS) and the Eye Tumor Research Foundation, Philadelphia, PA (CLS, JAS)

Conflict of Interest: No.

REFERENCES

1. Oleinick NL, Evans HH. The photobiology of photodynamic therapy: Cellular targets and mechanisms. Radiat Res. 1998;150:S146–56. [PubMed]
2. Henderson BW, Fingar VH. Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. Photochem Photobiol. 1989;49:299–304. [PubMed]
3. Fingar VH, Wieman TJ, Wiehle SA, Cerrito PB. The role of microvascular damage in photodynamic therapy: The effect of treatment on vessel constriction, permeability, and leukocyte adhesion. Cancer Res. 1992;52:4914–21. [PubMed]
4. Fingar VH. Vascular effects of photodynamic therapy. J Clin Laser Med Surg. 1996;14:323–8. [PubMed]
5. Schmidt-Erfurth UM, Michels S, Kusserow C, Jurklies B, Augustin AJ. Photodynamic therapy for symptomatic choroidal hemangioma: Visual and anatomic results. Ophthalmology. 2002;109:2284–94. [PubMed]
6. Landau IM, Steen B, Seregard S. Photodynamic therapy for circumscribed choroidal haemangioma. Acta Ophthalmol Scand. 2002;80:531–6. [PubMed]
7. Singh AD, Kaiser PK, Sears JE, Gupta M, Rundle PA, Rennie IG. Photodynamic therapy of circumscribed choroidal haemangioma. Br J Ophthalmol. 2004;88:1414–8. [PMC free article] [PubMed]
8. Boixadera A, García-Arumí J, Martínez-Castillo V, Encinas JL, Elizalde J, Blanco-Mateos G, et al. Prospective clinical trial evaluating the efficacy of photodynamic therapy for symptomatic circumscribed choroidal hemangioma. Ophthalmology. 2009;116:100–5. [PubMed]
9. Huiskamp EA, Müskens RP, Ballast A, Hooymans JM. Diffuse choroidal haemangioma in sturge-weber syndrome treated with photodynamic therapy under general anaesthesia. Graefes Arch Clin Exp Ophthalmol. 2005;243:727–30. [PubMed]
10. Gonzalez VH, Hu LK, Theodossiadis PG, Flotte TJ, Gragoudas ES, Young LH. Photodynamic therapy of pigmented choroidal melanomas. Invest Ophthalmol Vis Sci. 1995;36:871–8. [PubMed]
11. Barbazetto IA, Lee TC, Rollins IS, Chang S, Abramson DH. Treatment of choroidal melanoma using photodynamic therapy. Am J Ophthalmol. 2003;135:898–9. [PubMed]
12. Donaldson MJ, Lim L, Harper CA, Mackenzie J, Campbell G W. Primary treatment of choroidal amelanotic melanoma with photodynamic therapy. Clin Experiment Ophthalmol. 2005;33:548–9. [PubMed]
13. Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Laqua H. Benefits and complications of photodynamic therapy of papillary capillary hemangiomas. Ophthalmology. 2002;109:1256–66. [PubMed]
14. Aaberg TM, Jr, Aaberg TM, Sr, Martin DF, Gilman JP, Myles R. Three cases of large retinal capillary hemangiomas treated with verteporfin and photodynamic therapy. Arch Ophthalmol. 2005;123:328–32. [PubMed]
15. Ziemssen F, Voelker M, Inhoffen W, Bartz-Schmidt KU, Gelisken F. Combined treatment of a juxtapapillary retinal capillary haemangioma with intravitreal bevacizumab and photodynamic therapy. Eye (Lond) 2007;21:1125–6. [PubMed]
16. Mennel S, Meyer CH, Callizo J. Combined intravitreal anti-vascular endothelial growth factor (Avastin) and photodynamic therapy to treat retinal juxtapapillary capillary haemangioma. Acta Ophthalmol. 2009 [Epub ahead of print] [PubMed]
17. Blasi MA, Scupola A, Tiberti AC, Sasso P, Balestrazzi E. Photodynamic therapy for vasoproliferative retinal tumors. Retina. 2006;26:404–9. [PubMed]
18. Saldanha MJ, Edrich C. Treatment of vasoproliferative tumors with photodynamic therapy. Ophthalmic Surg Lasers Imaging. 2008;39:143–5. [PubMed]
19. Mennel S, Hausmann N, Meyer CH, Peter S. Photodynamic therapy for exudative hamartoma in tuberous sclerosis. Arch Ophthalmol. 2006;124:597–9. [PubMed]
20. Shields CL, Materin MA, Marr BP, Krepostman J, Shields JA. Resolution of exudative retinal detachment from retinal astrocytoma following photodynamic therapy. Arch Ophthalmol. 2008;126:273–4. [PubMed]
21. Eskelin S, Tommila P, Palosaari T, Kivelä T. Photodynamic therapy with verteporfin to induce regression of aggressive retinal astrocytomas. Acta Ophthalmol. 2008;86:794–9. [PubMed]
22. Holz ER, Linares L, Mieler WF, Weinberg DV. Exudative complications after photodynamic therapy. Arch Ophthalmol. 2003;121:1649–52. [PubMed]
23. Mennel S, Meyer CH, Eggarter F, Peter S. Transient serous retinal detachment in classic and occult choroidal neovascularization after photodynamic therapy. Am J Ophthalmol. 2005;140:758–60. [PubMed]
24. Jalil A, Mercieca K, Chaudhry NL, Stanga PE. Choroidal nonperfusion with significant subretinal exudation after PDT of predominantly classic CNV: An OCT and FFA study. Eur J Ophthalmol. 2009;19:490–3. [PubMed]
25. Tobita H, Ohno-Matsui K, Ogawa M, Kaneko Y, Shimada N, Mochizuki M. Transient serous retinal detachment after photodynamic therapy for polypoidal choroidal vasculopathy. Jpn J Ophthalmol. 2008;52:518–20. [PubMed]
26. Schmidt-Erfurth U, Laqua H, Schlötzer-Schrehard U, Viestenz A, Naumann GO. Histopathological changes following photodynamic therapy in human eyes. Arch Ophthalmol. 2002;120:835–44. [PubMed]
27. Schmidt-Erfurth U, Hasan T, Gragoudas E, Michaud N, Flotte TJ, Birngruber R. Vascular targeting in photodynamic occlusion of subretinal vessels. Ophthalmology. 1994;101:1953–61. [PubMed]
28. Schnurrbusch UE, Welt K, Horn LC, Wiedemann P, Wolf S. Histological findings of surgically excised choroidal neovascular membranes after photodynamic therapy. Br J Ophthalmol. 2001;85:1086–91. [PMC free article] [PubMed]
29. Ferrario A, Gomer CJ. Avastin enhances photodynamic therapy treatment of Kaposi’s sarcoma in a mouse tumor model. J Environ Pathol Toxicol Oncol. 2006;25:251–9. [PubMed]
30. Schmidt-Erfurth U, Schlötzer-Schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003;44:4473–80. [PubMed]

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