Middle East African Journal of Ophthalmology

CASE REPORT
Year
: 2013  |  Volume : 20  |  Issue : 1  |  Page : 83--86

Transient increased exudation after photodynamic therapy of intraocular tumors


Arman Mashayekhi, Carol L Shields, Jerry A Shields 
 Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USA

Correspondence Address:
Arman Mashayekhi
Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107
USA

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/m [2] body surface area) was delivered at a dose of 50 J/cm [2] and intensity of 600 mW/cm [2] 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.



How to cite this article:
Mashayekhi A, Shields CL, Shields JA. Transient increased exudation after photodynamic therapy of intraocular tumors.Middle East Afr J Ophthalmol 2013;20:83-86


How to cite this URL:
Mashayekhi A, Shields CL, Shields JA. Transient increased exudation after photodynamic therapy of intraocular tumors. Middle East Afr J Ophthalmol [serial online] 2013 [cited 2021 Dec 5 ];20:83-86
Available from: http://www.meajo.org/text.asp?2013/20/1/83/106400


Full Text

 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. [2],[3],[4] PDT has been used for the management of various intraocular tumors including circumscribed [5],[6],[7],[8] and diffuse choroidal hemangioma, [5],[6],[7],[8],[9] choroidal melanoma, [10],[11],[12] retinal hemangioblastoma, [13],[14],[15],[16] retinal vasoproliferative tumor, [17],[18] and retinal astrocytoma. [19],[20],[21] 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) [Figure 1]a and 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 1]c.

There was spontaneous recovery of BCVA to 20/25 and complete resolution of macular edema 3 weeks after PDT [Figure 1]d. 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}

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/m [2] ; 689 nm diode laser; 600 mW/cm [2] ; 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 [Figure 2]a and 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 2]c. 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 2]d. The patient required two more sessions of PDT during the subsequent 3 years for management of recurrent macular edema.{Figure 2}

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 [Figure 3]a and 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 3]c. 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 3]d. Subsequent tumor growth required treatment with I-125 plaque radiation.{Figure 3}

 Discussion



Increased exudation has been reported following PDT of ocular conditions other than tumors, including choroidal neovascular membrane (CNVM) and polypoidal choroidal vasculopathy. [22],[23],[24],[25] 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-workers [3] 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.

References

1Oleinick NL, Evans HH. The photobiology of photodynamic therapy: Cellular targets and mechanisms. Radiat Res 1998;150:S146-56.
2Henderson BW, Fingar VH. Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. Photochem Photobiol 1989;49:299-304.
3Fingar 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.
4Fingar VH. Vascular effects of photodynamic therapy. J Clin Laser Med Surg 1996;14:323-8.
5Schmidt-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.
6Landau IM, Steen B, Seregard S. Photodynamic therapy for circumscribed choroidal haemangioma. Acta Ophthalmol Scand 2002;80:531-6.
7Singh AD, Kaiser PK, Sears JE, Gupta M, Rundle PA, Rennie IG. Photodynamic therapy of circumscribed choroidal haemangioma. Br J Ophthalmol 2004;88:1414-8.
8Boixadera 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.
9Huiskamp 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.
10Gonzalez 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.
11Barbazetto IA, Lee TC, Rollins IS, Chang S, Abramson DH. Treatment of choroidal melanoma using photodynamic therapy. Am J Ophthalmol 2003;135:898-9.
12Donaldson MJ, Lim L, Harper CA, Mackenzie J, G Campbell W. Primary treatment of choroidal amelanotic melanoma with photodynamic therapy. Clin Experiment Ophthalmol 2005;33:548-9.
13Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Laqua H. Benefits and complications of photodynamic therapy of papillary capillary hemangiomas. Ophthalmology 2002;109:1256-66.
14Aaberg 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.
15Ziemssen 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.
16Mennel 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].
17Blasi MA, Scupola A, Tiberti AC, Sasso P, Balestrazzi E. Photodynamic therapy for vasoproliferative retinal tumors. Retina 2006;26:404-9.
18Saldanha MJ, Edrich C. Treatment of vasoproliferative tumors with photodynamic therapy. Ophthalmic Surg Lasers Imaging 2008;39:143-5.
19Mennel S, Hausmann N, Meyer CH, Peter S. Photodynamic therapy for exudative hamartoma in tuberous sclerosis. Arch Ophthalmol 2006;124:597-9.
20Shields 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.
21Eskelin S, Tommila P, Palosaari T, Kivelä T. Photodynamic therapy with verteporfin to induce regression of aggressive retinal astrocytomas. Acta Ophthalmol 2008;86:794-9.
22Holz ER, Linares L, Mieler WF, Weinberg DV. Exudative complications after photodynamic therapy. Arch Ophthalmol 2003;121:1649-52.
23Mennel 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.
24Jalil 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.
25Tobita 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.
26Schmidt-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.
27Schmidt-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.
28Schnurrbusch 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.
29Ferrario 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.
30Schmidt-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.