published_or_final_versionSpringer Open Choice, 21 Feb 201

AD Singh

Angie H. C. Fong

CC Chan

David Wong

Kenneth K. W. Li

MS Figueroa

P Steven

R Tzekov

S Grover

SJ Bakri

TD Warner

UM Schmidt-Erfurth

W Wang

Graefe s Archive for Clinical and Experimental Ophthalmology

English

PubMed

Springer - Publisher Connector

Intravitreal ranibizumab, photodynamic therapy, and vitreous surgery for the treatment of juxtapapillary retinal capillary hemangioma

Crossref

Fong, AHC

Li, KKW

Wong, D

HKU Scholars Hub

TitleIntravitreal ranibizumab, photodynamic therapy, and vitreoussurgery for the treatment of juxtapapillary retinal capillaryhemangiomaAuthor(s) Fong, AHC; Li, KKW; Wong, DCitation Graefe's Archive For Clinical And Experimental Ophthalmology,2011, v. 249 n. 4, p. 625-627Issued Date 2011URL http://hdl.handle.net/10722/145043Rights The Author(s)LETTER TO THE EDITORIntravitreal ranibizumab, photodynamic therapy,and vitreous surgery for the treatment of juxtapapillaryretinal capillary hemangiomaAngie H. C. Fong & Kenneth K. W. Li & David WongReceived: 31 August 2009 /Revised: 5 July 2010 /Accepted: 7 July 2010 /Published online: 31 July 2010# The Author(s) 2010. This article is published with open access at Springerlink.comDear Editor,Retinal capillary hemangiomas (RCH) are capillary angio-matous hamartomas of the retina and optic nerve head. Themedian age of diagnosing the disease is 31 years old [1].Although most RCH is isolated, 10–30% in the 31–40 agegroup are associated with Von Hippel Lindau disease(VHL). Up to 15% of RCHs are juxtapapillary, where mostare located temporally [2]. They are often associated withepiretinal membrane (ERM) formation and serous andtractional retinal detachment of the macula, which leads toa poor prognosis [1].We report a typical case of isolated juxtapapillary RCHthat underwent successful combined therapy with intra-vitreal ranibizumab injection and photodynamic therapy(PDT) 1 week before PPV and ERM peeling surgery.A 32-year-old woman presented with reduced right eyevision and metamorphopsia for 3 months. At presentation,her best-corrected visual acuity was 20/50 and 20/25 for theright and left eyes, respectively. Right eye fundus exami-nation revealed a reddish mass measuring 2.0 × 1.5 mm inthe inferotemporal juxtapapillary region associated withmacular subretinal fluid and ERM (Fig. 1a).Fundus fluorescein angiogram (FFA) showed earlyfilling of the lesion with late leakage into the subretinalspace. Anomalous vascular channels were seen sprout-ing from the lesion (Fig. 1b). Optical coherence tom-ography (OCT) confirmed serous detachment of themacula with vitreomacular traction (Fig. 1c). Centralfoveal thickness was increased to 570 µm (normalvalues=<315 µm) [3].A diagnosis of juxtapapillary retinal capillary hemangio-ma was made. Systemic workup for Von Hippel Lindau(VHL) disease did not reveal any other tumors. Her visualacuity continued to deteriorate to 20/100 in the subsequent2 months. She was treated once with PDT using standardfluence at that time, with reduced diameter laser spotcentering on the lesion avoiding the optic disc. There wasno clinical response and her vision continued to deteriorateto 20/200 3 months after the initial PDT. Combined therapy,using standard fluence PDT and intravitreal injection ofranibizumab were performed 2 months later (7 months sincepresentation). Reduction of lesion size (1.5 × 1.5 mm) andvascularity was noted 1 day after the combined therapy(Fig. 2a). One week later, PPV and ERM peel were carriedout and intravitreal triamcinolone injection (2 mg in0.05 ml) was given at the conclusion of surgery.The patient's visual acuity improved to 20/25 aftersuccessful surgery and the lesion remained stable for12 months, up to the latest follow-up (Fig. 2b). The centralfoveal thickness remained reduced within normal limits at324 μm. FFA showed hyperfluorescence in the late phase(Fig. 2c). A small superotemporal branch retinal veinFinancial and proprietary interests: NoneA. H. C. Fong :K. K. W. Li :D. WongDepartment of Ophthalmology, Queen Mary Hospital,Pokfulam,Hong Kong SAR, ChinaK. K. W. Li (*) :D. WongDepartment of Ophthalmology, United Christian Hospital,Kowloon,Hong Kong SAR, Chinae-mail: kennethli@rcsed.ac.ukK. K. W. Li :D. WongEye Institute, Li Ka Shing Faculty of Medicine,University of Hong Kong,Hong Kong SAR, ChinaGraefes Arch Clin Exp Ophthalmol (2011) 249:625–627DOI 10.1007/s00417-010-1453-3occlusion developed secondary to an iatrogenic breakresolved spontaneously.DiscussionTo date, no single modality in the treatment ofjuxtapapillary RCH has been particularly effective [1].Laser photocoagulation applied to the neural tissuesurrounding the tumor can cause permanent scotomas[2]. Use of cryotherapy is limited due to the posteriorlocation of the lesion.Anti-vascular endothelial growth factor (anti-VEGF)therapy has been reported to reduce vascular permeabilityby altering the balance of vaso-active cytokines like nitricFig. 2 Imaging results (color fundus photography and FFA) of thepatient after combined treatment with injection of ranibizumab, PDT,and intravitreal surgery. a Day 1 after combined intravitrealranibizumab injection and PDT, showing regression of the tumor aswell as marked decrease in vascularity and exudation. b Post-operative(month 2) fundus photograph showing relief of traction on the maculaafter removal of the epiretinal membrane and reduction in size of theangioma. A peripheral branch retinal vein occlusion (white arrows)resulted from a small iatrogenic break. c Late phase of fundusflourescein angiography (month 12) showing staining of the lesionwith minimal leakageFig. 1 Imaging results (color fundus photography, FFA and OCT) ofthe patient at initial presentation. a Fundus photograph of the right eyeshowing juxtapapillary retinal capillary hemangioma, measured 2.0×1.5 mm, located inferotemporal to the optic disc. b Fundus fluoresceinangiography demonstrating hyperflourescence of the lesion as well aslate leakage into submacular space. c OCT (horizontal 5-mm scanacross the fovea) showing macular detachment secondary to vitre-omacular traction626 Graefes Arch Clin Exp Ophthalmol (2011) 249:625–627oxide and endothelin-1 [4] or by directly altering endothe-lial tight junction proteins [5]. It is postulated that excessiveaccumulation of hypoxic induced factor (HIF) in theneoplastic stromal cells of RCH leads to the production ofother angiogenic factors that are able to maintain andpromote the growth of primary hemangiomas [6].PDT is shown to be effective in causing fibrosis andinvolution of the primary angioma, but its use on peri-papillary area is limited by vaso-occlusive effects [2, 7].For larger tumors, verteporfin may only be activated onthe surface of the tumor, and the reactive oxygen speciesmay not cause closure of deeper tumor vessels. Bycombining anti-VEGF with reduced fluence PDT, theoutline of the primary angioma can be better delineatedand may thus reduce the energy and the treatment area,thereby minimizing the damage to the neurological tissues[8]. Recent reports of combined therapy with anti-VEGFtherapy and PDT have shown promising results in theselesions [7].Anti-VEGF agents, like bevacizumab, have beenreported as a useful pre-operative adjunct in the surgicaltreatment of proliferative diabetic retinopathy, with signif-icant reduction in neovascularization, bleeding, and adher-ence of fibrovascular complex to the retina [9]. We foundthat ranibizumab is useful in the present case. Combinedtreatment with anti-VEGF and PDT 1 week before surgerycaused a reduction in macular edema, which reduced therisk of retinal cyst rupture during peeling procedure [10].Reduced tumor vascularization may have lowered the riskof intraoperative bleeding.In summary, pre-operative combination therapy with ananti-VEGF agent and PDT, PPV, and ERM followed byintravitreal triamcinolone at the conclusion of surgery led toimprovement in visual outcome. The use of triple therapywas recently shown to be effective in the treatment of age-related macular degeneration and our case may suggest thata multi-faceted approach could be beneficial in cases ofjuxtapapillary RCH [11].Open Access This article is distributed under the terms of the CreativeCommons Attribution Noncommercial License which permits anynoncommercial use, distribution, and reproduction in any medium,provided the original author(s) and source are credited.References1. Singh AD, Nouri M, Shields CL, Shields JA, Perez N (2002)Treatment of retinal capillary hemangioma. Ophthalmology 109(10):1799–18062. Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Laqua H (2002)Benefits and complications of photodynamic therapy of papillarycapillary hemangiomas. Ophthalmology 109(7):1256–12663. Grover S, Murthy RK et al (2009) Normative data for macularthickness by high-definition spectral-domain optical coherencetomography (spectralis). Am J Ophthalmol 148(2):266–2714. Warner TD (1999) Relationships between the endothelin and nitricoxide pathways. Clin Exp Pharmacol Physiol 26(3):247–2525. WangW, Dentler WL, Borchardt RT (2001) VEGF increases BMECmonolayer permeability by affecting occludin expression and tightjunction assembly. Am J Physiol Heart Circ Physiol 280(1):434–4406. Chan CC, Collins AB, Chew EY (2007)Molecular pathology of eyeswith von Hippel-Lindau (VHL) disease: a review. Retina 27(1):1–77. Mennel S, Meyer CH, Callizo J (2009) Combined intravitreal anti-vascular endothelial growth factor (Avastin) and photodynamictherapy to treat retinal juxtapapillary capillary haemangioma. ActaOphthalmol Feb 12 [Epub ahead of print]8. Tzekov R, Lin T, Zhang KM, Jackson B, Oyejide A, Orilla W,Kulkarni AD, Kuppermann BD, Wheeler L, Burke J (2006)Ocular changes after photodynamic therapy. Invest OphthalmolVis Sci 47(1):377–3859. Figueroa MS, Contreras I, Noval S (2009) Anti-angiogenic drugsas an adjunctive therapy in the surgical treatment of diabeticretinopathy. Curr Diabetes Rev 5(1):52–5610. Steven P, Laqua H, Wong D, Hoerauf H (2006) Secondaryparacentral retinal holes following internal limiting membraneremoval. Br J Ophthalmol 90(3):293–29511. Bakri SJ, Couch SM et al (2009) Same-day triple therapy withphotodynamic therapy, intravitreal dexamethasone, and bevacizumabin wet age-related macular degeneration. Retina 29(5):573–578Graefes Arch Clin Exp Ophthalmol (2011) 249:625–627 627

LETTER TO THE EDITOR
Intravitreal ranibizumab, photodynamic therapy,
and vitreous surgery for the treatment of juxtapapillary
retinal capillary hemangioma
Angie H. C. Fong & Kenneth K. W. Li & David Wong
Received: 31 August 2009 /Revised: 5 July 2010 /Accepted: 7 July 2010 /Published online: 31 July 2010
# The Author(s) 2010. This article is published with open access at Springerlink.com
Dear Editor,
Retinal capillary hemangiomas (RCH) are capillary angio-
matous hamartomas of the retina and optic nerve head. The
median age of diagnosing the disease is 31 years old [1].
Although most RCH is isolated, 10–30% in the 31–40 age
group are associated with Von Hippel Lindau disease
(VHL). Up to 15% of RCHs are juxtapapillary, where most
are located temporally [2]. They are often associated with
epiretinal membrane (ERM) formation and serous and
tractional retinal detachment of the macula, which leads to
a poor prognosis [1].
We report a typical case of isolated juxtapapillary RCH
that underwent successful combined therapy with intra-
vitreal ranibizumab injection and photodynamic therapy
(PDT) 1 week before PPV and ERM peeling surgery.
A 32-year-old woman presented with reduced right eye
vision and metamorphopsia for 3 months. At presentation,
her best-corrected visual acuity was 20/50 and 20/25 for the
right and left eyes, respectively. Right eye fundus exami-
nation revealed a reddish mass measuring 2.0 × 1.5 mm in
the inferotemporal juxtapapillary region associated with
macular subretinal fluid and ERM (Fig. 1a).
Fundus fluorescein angiogram (FFA) showed early
filling of the lesion with late leakage into the subretinal
space. Anomalous vascular channels were seen sprout-
ing from the lesion (Fig. 1b). Optical coherence tom-
ography (OCT) confirmed serous detachment of the
macula with vitreomacular traction (Fig. 1c). Central
foveal thickness was increased to 570 µm (normal
values=<315 µm) [3].
A diagnosis of juxtapapillary retinal capillary hemangio-
ma was made. Systemic workup for Von Hippel Lindau
(VHL) disease did not reveal any other tumors. Her visual
acuity continued to deteriorate to 20/100 in the subsequent
2 months. She was treated once with PDT using standard
fluence at that time, with reduced diameter laser spot
centering on the lesion avoiding the optic disc. There was
no clinical response and her vision continued to deteriorate
to 20/200 3 months after the initial PDT. Combined therapy,
using standard fluence PDT and intravitreal injection of
ranibizumab were performed 2 months later (7 months since
presentation). Reduction of lesion size (1.5 × 1.5 mm) and
vascularity was noted 1 day after the combined therapy
(Fig. 2a). One week later, PPV and ERM peel were carried
out and intravitreal triamcinolone injection (2 mg in
0.05 ml) was given at the conclusion of surgery.
The patient's visual acuity improved to 20/25 after
successful surgery and the lesion remained stable for
12 months, up to the latest follow-up (Fig. 2b). The central
foveal thickness remained reduced within normal limits at
324 μm. FFA showed hyperfluorescence in the late phase
(Fig. 2c). A small superotemporal branch retinal vein
Financial and proprietary interests: None
A. H. C. Fong :K. K. W. Li :D. Wong
Department of Ophthalmology, Queen Mary Hospital,
Pokfulam,
Hong Kong SAR, China
K. K. W. Li (*) :D. Wong
Department of Ophthalmology, United Christian Hospital,
Kowloon,
Hong Kong SAR, China
e-mail: kennethli@rcsed.ac.uk
K. K. W. Li :D. Wong
Eye Institute, Li Ka Shing Faculty of Medicine,
University of Hong Kong,
Hong Kong SAR, China
Graefes Arch Clin Exp Ophthalmol (2011) 249:625–627
DOI 10.1007/s00417-010-1453-3
occlusion developed secondary to an iatrogenic break
resolved spontaneously.
Discussion
To date, no single modality in the treatment of
juxtapapillary RCH has been particularly effective [1].
Laser photocoagulation applied to the neural tissue
surrounding the tumor can cause permanent scotomas
[2]. Use of cryotherapy is limited due to the posterior
location of the lesion.
Anti-vascular endothelial growth factor (anti-VEGF)
therapy has been reported to reduce vascular permeability
by altering the balance of vaso-active cytokines like nitric
Fig. 2 Imaging results (color fundus photography and FFA) of the
patient after combined treatment with injection of ranibizumab, PDT,
and intravitreal surgery. a Day 1 after combined intravitreal
ranibizumab injection and PDT, showing regression of the tumor as
well as marked decrease in vascularity and exudation. b Post-operative
(month 2) fundus photograph showing relief of traction on the macula
after removal of the epiretinal membrane and reduction in size of the
angioma. A peripheral branch retinal vein occlusion (white arrows)
resulted from a small iatrogenic break. c Late phase of fundus
flourescein angiography (month 12) showing staining of the lesion
with minimal leakage
Fig. 1 Imaging results (color fundus photography, FFA and OCT) of
the patient at initial presentation. a Fundus photograph of the right eye
showing juxtapapillary retinal capillary hemangioma, measured 2.0×
1.5 mm, located inferotemporal to the optic disc. b Fundus fluorescein
angiography demonstrating hyperflourescence of the lesion as well as
late leakage into submacular space. c OCT (horizontal 5-mm scan
across the fovea) showing macular detachment secondary to vitre-
omacular traction
626 Graefes Arch Clin Exp Ophthalmol (2011) 249:625–627
oxide and endothelin-1 [4] or by directly altering endothe-
lial tight junction proteins [5]. It is postulated that excessive
accumulation of hypoxic induced factor (HIF) in the
neoplastic stromal cells of RCH leads to the production of
other angiogenic factors that are able to maintain and
promote the growth of primary hemangiomas [6].
PDT is shown to be effective in causing fibrosis and
involution of the primary angioma, but its use on peri-
papillary area is limited by vaso-occlusive effects [2, 7].
For larger tumors, verteporfin may only be activated on
the surface of the tumor, and the reactive oxygen species
may not cause closure of deeper tumor vessels. By
combining anti-VEGF with reduced fluence PDT, the
outline of the primary angioma can be better delineated
and may thus reduce the energy and the treatment area,
thereby minimizing the damage to the neurological tissues
[8]. Recent reports of combined therapy with anti-VEGF
therapy and PDT have shown promising results in these
lesions [7].
Anti-VEGF agents, like bevacizumab, have been
reported as a useful pre-operative adjunct in the surgical
treatment of proliferative diabetic retinopathy, with signif-
icant reduction in neovascularization, bleeding, and adher-
ence of fibrovascular complex to the retina [9]. We found
that ranibizumab is useful in the present case. Combined
treatment with anti-VEGF and PDT 1 week before surgery
caused a reduction in macular edema, which reduced the
risk of retinal cyst rupture during peeling procedure [10].
Reduced tumor vascularization may have lowered the risk
of intraoperative bleeding.
In summary, pre-operative combination therapy with an
anti-VEGF agent and PDT, PPV, and ERM followed by
intravitreal triamcinolone at the conclusion of surgery led to
improvement in visual outcome. The use of triple therapy
was recently shown to be effective in the treatment of age-
related macular degeneration and our case may suggest that
a multi-faceted approach could be beneficial in cases of
juxtapapillary RCH [11].
Open Access This article is distributed under the terms of the Creative
Commons Attribution Noncommercial License which permits any
noncommercial use, distribution, and reproduction in any medium,
provided the original author(s) and source are credited.
References
1. Singh AD, Nouri M, Shields CL, Shields JA, Perez N (2002)
Treatment of retinal capillary hemangioma. Ophthalmology 109
(10):1799–1806
2. Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Laqua H (2002)
Benefits and complications of photodynamic therapy of papillary
capillary hemangiomas. Ophthalmology 109(7):1256–1266
3. Grover S, Murthy RK et al (2009) Normative data for macular
thickness by high-definition spectral-domain optical coherence
tomography (spectralis). Am J Ophthalmol 148(2):266–271
4. Warner TD (1999) Relationships between the endothelin and nitric
oxide pathways. Clin Exp Pharmacol Physiol 26(3):247–252
5. WangW, Dentler WL, Borchardt RT (2001) VEGF increases BMEC
monolayer permeability by affecting occludin expression and tight
junction assembly. Am J Physiol Heart Circ Physiol 280(1):434–440
6. Chan CC, Collins AB, Chew EY (2007)Molecular pathology of eyes
with von Hippel-Lindau (VHL) disease: a review. Retina 27(1):1–7
7. Mennel S, Meyer CH, Callizo J (2009) Combined intravitreal anti-
vascular endothelial growth factor (Avastin) and photodynamic
therapy to treat retinal juxtapapillary capillary haemangioma. Acta
Ophthalmol Feb 12 [Epub ahead of print]
8. Tzekov R, Lin T, Zhang KM, Jackson B, Oyejide A, Orilla W,
Kulkarni AD, Kuppermann BD, Wheeler L, Burke J (2006)
Ocular changes after photodynamic therapy. Invest Ophthalmol
Vis Sci 47(1):377–385
9. Figueroa MS, Contreras I, Noval S (2009) Anti-angiogenic drugs
as an adjunctive therapy in the surgical treatment of diabetic
retinopathy. Curr Diabetes Rev 5(1):52–56
10. Steven P, Laqua H, Wong D, Hoerauf H (2006) Secondary
paracentral retinal holes following internal limiting membrane
removal. Br J Ophthalmol 90(3):293–295
11. Bakri SJ, Couch SM et al (2009) Same-day triple therapy with
photodynamic therapy, intravitreal dexamethasone, and bevacizumab
in wet age-related macular degeneration. Retina 29(5):573–578
Graefes Arch Clin Exp Ophthalmol (2011) 249:625–627 627


Benefits and complications of photodynamic therapy of papillary capillary hemangiomas.

ChanCC,CollinsAB,ChewEY(2007)Molecularpathologyofeyes with von Hippel-Lindau (VHL) disease: a review.

Combined intravitreal antivascular endothelial growth factor (Avastin) and photodynamic therapy to treat retinal juxtapapillary capillary haemangioma.

Murthy RK et al (2009) Normative data for macular thickness by high-definition spectral-domain optical coherence tomography (spectralis).

Ocular changes after photodynamic therapy.

Relationships between the endothelin and nitric oxide pathways.

Treatment of retinal capillary hemangioma.

VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly.

https://link.springer.com/content/pdf/10.1007%2Fs00417-010-1453-3.pdf

Intravitreal ranibizumab, photodynamic therapy, and vitreous surgery for the treatment of juxtapapillary retinal capillary hemangioma

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

Crossref

HKU Scholars Hub

Springer - Publisher Connector