- Email: [email protected]
Combined hamartoma of the retina and retinal pigment epithelium. Anti-VEGF treatment of the associated choroidal neovascular membranes
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Short communication
Combined hamartoma of the retina and retinal pigment epithelium. Anti-VEGF treatment of the associated choroidal neovascular membranes夽,夽夽 L. Echevarría ∗ , O. Villena, T. Nievas, R. Bellido FEA de UGC Oftalmología, Hospital Comarcal de la Axarquía, Málaga, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history:
Case report: A 58-year-old female was diagnosed with a juxtapapillary combined hamartoma
Received 25 June 2014
of the retina and retinal pigment epithelium (CHR–RPE) in her left eye 14 years ago. Her visual
Accepted 30 September 2014
acuity in that eye was 20/20. Recently, she came to our department with a sudden visual
Available online 10 April 2015
loss and metamorphopsia in her left eye. After performing funduscopy, angiography and OCT, she was diagnosed with choroidal neovascular membrane (CNVM) at lesion border,
Keywords:
and started on antiangiogenic therapy.
Hamartoma
Discussion: CHR–RPE, despite being a benign condition, may become complicated with severe
Choroidal neovascularization
visual impairment. Antiangiogenic therapy provides a good alternative to photodynamic
Membranes
therapy or laser photocoagulation for treatment of CNVM, avoiding adding iatrogenesis from
Anti-VEGF
these treatments to the complications associated with this pathology.
Iatrogenic
˜ © 2014 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Hamartoma combinado de retina y del epitelio pigmentario. Abordaje mediante terapia anti-VEGF de membranas neovasculares asociadas r e s u m e n Palabras clave:
˜ Caso clínico: Paciente de 58 anos diagnosticada de hamartoma combinado del epitelio pig-
Hamartoma
˜ mentario retiniano (CHRRPE) yuxtapapilar unilateral en ojo izquierdo hace 14 anos, con
Neovascularización coroidea
máxima agudeza visual. Acude con pérdida de visión brusca y metamorfopsias en dicho
Membranas
ojo. Tras funduscopia, angiografía y OCT se diagnostica membrana neovascular coroidea
Anti-VEGF
(MNVC) en el borde de la lesión, y se inicia terapia antiangiogénica.
Iatrogenia
Discusión: El CHRRPE, aunque benigno, puede complicarse produciendo gran deterioro visual. Los antiangiogénicos son buena opción frente a terapia fotodinámica o a
夽 Please cite this article as: Echevarría L, Villena O, Nievas T, Bellido R. Hamartoma combinado de retina y del epitelio pigmentario. Abordaje mediante terapia anti-VEGF de membranas neovasculares asociadas. Arch Soc Esp Oftalmol. 2015;90:87-93. 夽夽 Clinic case presented at the 90th Congress of the Ophthalmology Society of Spain, Bilbao, 2014. ∗ Corresponding author. E-mail addresses: [email protected], [email protected] (L. Echevarría). ˜ 2173-5794/© 2014 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
88
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
fotocoagulación láser para tratar las MNVC, evitando sumar la iatrogenia del tratamiento a complicaciones propias de la patología. ˜ de Oftalmología. Publicado por Elsevier España, S.L.U. Todos © 2014 Sociedad Espanola los derechos reservados.
Introduction Combined hamartoma of the retina and the retinal pigment epithelium (CHR–RPE) is an infrequent, presumably benign congenital malformation with unilateral expression. It appears in healthy individuals and occasionally in patients with type 2 neurofibromatosis and Gorlin-Goltz syndrome.1,2 It can be associated to fossa, drusen or papilla coloboma,3 in addition to being frequently juxtapapillary. Histologically, it presents membranes in the retinal pigment epithelium, neurosensory retina, retinal blood vessels and vitreous-retina in varying degrees. It is frequently diagnosed as a casual finding as it does not usually involve the eyesight.4,5 However, in 10% of cases vision deteriorates severely, with complications derived from epiretinal tractions, formation of hard exudates and occasionally choroidal neovascularization at the edges of the lesion.2,6,7
Clinic case The authors addressed the case of a female, 58, diagnosed 14 years ago with CHR–RPE in the left eye during a routine examination. Visual acuity in both eyes was 1, and the patient exhibited only a small altitudinal scotoma in the visual field of the left eye. After regular follow-up, she visited 5 months ago due to metamorphopsia in the left eye and visual acuity of only 0.08. Left eye ophthalmoscopy revealed an image compatible with juxtapapillary hamartoma together with choroidal neovascular membrane (CNVM) at the edge of the lesion (parapapillary), associated to hemorrhage and serous detachment (Fig. 1). This finding was confirmed with angiography (Fig. 2) and posterior
OCT (Fig. 3) of said eye. Right eye examinations gave normal results. As the lesion was located in the papilomacular area, intravitreal anti-VEGF injections were indicated (ranibizumab, 10 mg/ml), applied in 3 injections at one-month intervals. The first was applied on December 10, and the patient was examined with retinographs one month later (Fig. 4A), which revealed some activity of the lesion. The second intravitreal anti-VEGF injection was administered on January 14, with subsequent retinograph examination one month later (Fig. 4B). On this occasion, moderate activity reduction was observed. The last antiangiogenic application was administered February 18, with another retinographic examination one month later (Fig. 5), achieving cicatrization of the lesion, the disappearance of hemorrhages and of serous detachment. However, significant subretinal fibrosis remained. In addition, a new OCT was performed which determined the inactivation of the neovascular lesion (Fig. 6). Due to residual atrophic-degenerative changes, visual acuity only recovered up to 0.1, but anatomic improvements were achieved as well as diminished metamorphopsia and halting the progression of the lesion.
Discussion CHR–RPE is regarded as an untreatable benign tumor. However, some of its complications can be devastating and cause significant visual loss. CNVM in papilomacular and subfoveal areas associated to juxtapapillary CHR–RPE, treated in the past with photocoagulation or photodynamic therapy2,3,6,8 produced huge central iatrogenic scotoma. However, at present these can be approached with anti-VEGF therapies with the advantage that they do not produce scars over the retina.
Fig. 1 – Funduscopy showing image is compatible with juxtapapillary hamartoma associated to choroidal neovascular membrane (CNVM) at the edge of the lesion, accompanied by hemorrhages and serous detachment.
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
Fig. 2 – In early and subsequently later times, angiographs show active neovascular membrane at the edge of the hamartoma. There are 2 traction choroidal folds along the posterior pole, possibly produced by the membranes associated to the tumor.
89
90
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
Macula thickness: Macular cube 512x128
OD
OS
500 263 400 300
337 500 493 298 256 301
200 269 100 256
Fovea: 321. 64
ILM-RPE Thickness (µm)
0 µm
Overlay: ILM-RPE transparency: 50% High-definition mode
ILM-RPE
N
T ILM
Distribution of normals 99% 95% 5% 1% RPE
S
I
ILM-RPE
Central subfield thickness (µm)
Cube volume (mm3)
Cube average thickness (µm)
298
12.3
340
Clinical history (anamnesis-current disease) Referred from Axarquia hospital for macular OCT, diagnosed with LE hamartoma. Visited Emergency Service due to loss of viion. Papillary venous loop and paripapillary serous detachment and hemorrhage. FAG in referring hospita: overflowing serous detach. Supplementary tests: Macular CT: RE: reflexivity alteration in external retina with tomographic appearance of small drusen dispersed throughout the macular area. Choroidal folds in inferior macular periphery. LE: tomographic image compatible with CNVM in nasal region of macula (parapapillary) extending to subfoveal region, with exudative activity signs. Accordingly, antiangiogenic intravitreal treatment is recommended ASAP.
Málaga, Nov. 12, 2013 Fig. 3 – Left eye OCT showing CNVM in the nasal region of the macula with signs of exudative activity.
The utilization of intravitreal ranibizumab injections, extensively applied in approaches to macular degeneration and other diseases, was not broadly described in the scientific literature for CNVM associated to juxtapapillary CHR–RPE.
This treatment can counteract the progression of the lesion and avoids adding iatrogeny to the damages caused by the pathology itself. On the other hand, in some cases it is possible to combine different therapies such as vitrectomy
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
91
Fig. 4 – (A) Retinographs one month after the first intravitreal injection, showing activity of the lesion with initial cicatrization. (B) Retinographs one month after the second intravitreal injection, showing moderate reduction in the activity.
Fig. 5 – Retinographs one month after the third injection, showing lesion cicatrization, disappearance of hemorrhages and of serous detachment, with significant subregional residual fibrosis remaining.
92
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
OD
Macula thickness: Macular cube 512x128
OS
500 250 400
300
305 410
398 117 152
202
316 200 277 100 256
ILM-RPE Thickness (µm)
Fovea: fovea not found
0µm
Overlay: ILM-RPE transparency: 50% High-definition mode
ILM-RPE
N
T
ILM
Distribution of normals 99% 95% 5% 1% RPE S Central subfield Cube volume Cube average (mm3) thickness (µm) thickness (µm) I
ILM-RPE
117
9.5
264
Clinical history (anamnesis-current disease) Referred from Axarquia hospital for macular OCT, CNVM associated to LE optic nerve hamartoma, treated with 3 doses (latest Feb. 18, 2014). Supplementary tests: Macular OCT: highly arteracted with continuous blinking and inability to fix gaze, even with RE. RE: no significant changes from previous OCT. LE: Image compatible with subretinal fibrosis. Minimum amount of LSR (a lot less than previous OCT). Atrophic-degenerative changes, making it difficult to precisely determine degree of activity: although the impression is more like residuals, assess on basis of clinic and/or FAG activity. Málaga, May 19, 2014 Fig. 6 – New OCT which determined considerable deactivation of the neovascular lesion, with disappearance of liquid associated thereto. It also shows subretinal fibrosis and residual atrophic-degenerative changes.
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
or surgical approach of epiretinal membranes, when several CHR–RPE complications are associated in the same eye,9,10 even though and despite all the obstacles modest visual results can be obtained due to the severity of the sequels left by associated diseases.
Conflict of interest No conflict of interests has been declared by the authors.
5.
6.
7.
references
1. Badami A, Bianciotto CG, Shields C, Shields JA. Combined hamartoma of the retina and retinal pigment epithelium in a child with branchial cleft cysts. J Pediatr Ophthalmol Strabismus. 2012;49:e9–11. 2. Xue K, Mellington F, Gout I, Rokerya S, Olurin OI, El-Amir A. Combined hamartoma of the retina and retinal pigment epithelium. BMJ Case Rep. 2012;2012. S1757-790X. 3. Chang YC, Tsai RK. Coexistence of optic nerve head drusen and combined hamartoma of the retina and retinal pigment epithelium in a Taiwanese male. Kaohsiung J Med Sci. 2009;25:40–3. 4. Nowomiejska K, Zarnowski T, Rejdak R, Juenemann A. Combined hamartoma of the optic disc and retinal pigment
8.
9.
10.
93
epithelium – 3 years of the follow-up with semi-automated kinetic perimetry. Open J Ophthalmol. 2012;2:116–8. Nowomiejska K, Vonthein R, Patzold J, Krapp E, Rejdak R, Zarnowski T, et al. Comparison between semiautomated kinetic perimetry and conventional Goldmann manual kinetic perimetry in advanced visual field loss. Ophthalmology. 2005;112:343–54. Mateo C, Moreno JG, Lechuga M, Adán A, Corcóstegui B. Surgical removal of peripapillary choroidal neovascularization associated with optic nerve drusen. Retina. 2004;24:739–45. Pérez-Álvarez MJ, Escalada-Ferrándiz A, Hernández-García E, Moreno-López M, García Sánchez J. Hallazgos clínicos y tomográficos en el hamartoma combinado de retina y epitelio pigmentado retiniano: 2 casos. Studium Ophthalmologicum. 2009;XXVII:105–8. Cilliers H, Harper CA. Photodynamic therapy with verteporfin for vascular leakage from a combined hamartoma of the retina and retinal pigment epithelium. Clin Experiment Ophthalmol. 2006;34:186–8. Pérez-Álvarez MJ, Alejandre-Alba N, García-Sánchez J. Hamartoma combinado de retina y epitelio pigmentario retiniano. Diagnóstico mediante tomografía de coherencia óptica y angiofluoresceingrafía. Arch Soc Esp Oftalmol. 2008;83:193–6. Stallman JB. Visual improvement alter pars plana vitrectomy and membrane peeling for vitreoretinal traction associated with combined hamartoma of the retina and retinal pigment epithelium. Retina. 2002;22:101–4.
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Short communication
Combined hamartoma of the retina and retinal pigment epithelium. Anti-VEGF treatment of the associated choroidal neovascular membranes夽,夽夽 L. Echevarría ∗ , O. Villena, T. Nievas, R. Bellido FEA de UGC Oftalmología, Hospital Comarcal de la Axarquía, Málaga, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history:
Case report: A 58-year-old female was diagnosed with a juxtapapillary combined hamartoma
Received 25 June 2014
of the retina and retinal pigment epithelium (CHR–RPE) in her left eye 14 years ago. Her visual
Accepted 30 September 2014
acuity in that eye was 20/20. Recently, she came to our department with a sudden visual
Available online 10 April 2015
loss and metamorphopsia in her left eye. After performing funduscopy, angiography and OCT, she was diagnosed with choroidal neovascular membrane (CNVM) at lesion border,
Keywords:
and started on antiangiogenic therapy.
Hamartoma
Discussion: CHR–RPE, despite being a benign condition, may become complicated with severe
Choroidal neovascularization
visual impairment. Antiangiogenic therapy provides a good alternative to photodynamic
Membranes
therapy or laser photocoagulation for treatment of CNVM, avoiding adding iatrogenesis from
Anti-VEGF
these treatments to the complications associated with this pathology.
Iatrogenic
˜ © 2014 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Hamartoma combinado de retina y del epitelio pigmentario. Abordaje mediante terapia anti-VEGF de membranas neovasculares asociadas r e s u m e n Palabras clave:
˜ Caso clínico: Paciente de 58 anos diagnosticada de hamartoma combinado del epitelio pig-
Hamartoma
˜ mentario retiniano (CHRRPE) yuxtapapilar unilateral en ojo izquierdo hace 14 anos, con
Neovascularización coroidea
máxima agudeza visual. Acude con pérdida de visión brusca y metamorfopsias en dicho
Membranas
ojo. Tras funduscopia, angiografía y OCT se diagnostica membrana neovascular coroidea
Anti-VEGF
(MNVC) en el borde de la lesión, y se inicia terapia antiangiogénica.
Iatrogenia
Discusión: El CHRRPE, aunque benigno, puede complicarse produciendo gran deterioro visual. Los antiangiogénicos son buena opción frente a terapia fotodinámica o a
夽 Please cite this article as: Echevarría L, Villena O, Nievas T, Bellido R. Hamartoma combinado de retina y del epitelio pigmentario. Abordaje mediante terapia anti-VEGF de membranas neovasculares asociadas. Arch Soc Esp Oftalmol. 2015;90:87-93. 夽夽 Clinic case presented at the 90th Congress of the Ophthalmology Society of Spain, Bilbao, 2014. ∗ Corresponding author. E-mail addresses: [email protected], [email protected] (L. Echevarría). ˜ 2173-5794/© 2014 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
88
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
fotocoagulación láser para tratar las MNVC, evitando sumar la iatrogenia del tratamiento a complicaciones propias de la patología. ˜ de Oftalmología. Publicado por Elsevier España, S.L.U. Todos © 2014 Sociedad Espanola los derechos reservados.
Introduction Combined hamartoma of the retina and the retinal pigment epithelium (CHR–RPE) is an infrequent, presumably benign congenital malformation with unilateral expression. It appears in healthy individuals and occasionally in patients with type 2 neurofibromatosis and Gorlin-Goltz syndrome.1,2 It can be associated to fossa, drusen or papilla coloboma,3 in addition to being frequently juxtapapillary. Histologically, it presents membranes in the retinal pigment epithelium, neurosensory retina, retinal blood vessels and vitreous-retina in varying degrees. It is frequently diagnosed as a casual finding as it does not usually involve the eyesight.4,5 However, in 10% of cases vision deteriorates severely, with complications derived from epiretinal tractions, formation of hard exudates and occasionally choroidal neovascularization at the edges of the lesion.2,6,7
Clinic case The authors addressed the case of a female, 58, diagnosed 14 years ago with CHR–RPE in the left eye during a routine examination. Visual acuity in both eyes was 1, and the patient exhibited only a small altitudinal scotoma in the visual field of the left eye. After regular follow-up, she visited 5 months ago due to metamorphopsia in the left eye and visual acuity of only 0.08. Left eye ophthalmoscopy revealed an image compatible with juxtapapillary hamartoma together with choroidal neovascular membrane (CNVM) at the edge of the lesion (parapapillary), associated to hemorrhage and serous detachment (Fig. 1). This finding was confirmed with angiography (Fig. 2) and posterior
OCT (Fig. 3) of said eye. Right eye examinations gave normal results. As the lesion was located in the papilomacular area, intravitreal anti-VEGF injections were indicated (ranibizumab, 10 mg/ml), applied in 3 injections at one-month intervals. The first was applied on December 10, and the patient was examined with retinographs one month later (Fig. 4A), which revealed some activity of the lesion. The second intravitreal anti-VEGF injection was administered on January 14, with subsequent retinograph examination one month later (Fig. 4B). On this occasion, moderate activity reduction was observed. The last antiangiogenic application was administered February 18, with another retinographic examination one month later (Fig. 5), achieving cicatrization of the lesion, the disappearance of hemorrhages and of serous detachment. However, significant subretinal fibrosis remained. In addition, a new OCT was performed which determined the inactivation of the neovascular lesion (Fig. 6). Due to residual atrophic-degenerative changes, visual acuity only recovered up to 0.1, but anatomic improvements were achieved as well as diminished metamorphopsia and halting the progression of the lesion.
Discussion CHR–RPE is regarded as an untreatable benign tumor. However, some of its complications can be devastating and cause significant visual loss. CNVM in papilomacular and subfoveal areas associated to juxtapapillary CHR–RPE, treated in the past with photocoagulation or photodynamic therapy2,3,6,8 produced huge central iatrogenic scotoma. However, at present these can be approached with anti-VEGF therapies with the advantage that they do not produce scars over the retina.
Fig. 1 – Funduscopy showing image is compatible with juxtapapillary hamartoma associated to choroidal neovascular membrane (CNVM) at the edge of the lesion, accompanied by hemorrhages and serous detachment.
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
Fig. 2 – In early and subsequently later times, angiographs show active neovascular membrane at the edge of the hamartoma. There are 2 traction choroidal folds along the posterior pole, possibly produced by the membranes associated to the tumor.
89
90
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
Macula thickness: Macular cube 512x128
OD
OS
500 263 400 300
337 500 493 298 256 301
200 269 100 256
Fovea: 321. 64
ILM-RPE Thickness (µm)
0 µm
Overlay: ILM-RPE transparency: 50% High-definition mode
ILM-RPE
N
T ILM
Distribution of normals 99% 95% 5% 1% RPE
S
I
ILM-RPE
Central subfield thickness (µm)
Cube volume (mm3)
Cube average thickness (µm)
298
12.3
340
Clinical history (anamnesis-current disease) Referred from Axarquia hospital for macular OCT, diagnosed with LE hamartoma. Visited Emergency Service due to loss of viion. Papillary venous loop and paripapillary serous detachment and hemorrhage. FAG in referring hospita: overflowing serous detach. Supplementary tests: Macular CT: RE: reflexivity alteration in external retina with tomographic appearance of small drusen dispersed throughout the macular area. Choroidal folds in inferior macular periphery. LE: tomographic image compatible with CNVM in nasal region of macula (parapapillary) extending to subfoveal region, with exudative activity signs. Accordingly, antiangiogenic intravitreal treatment is recommended ASAP.
Málaga, Nov. 12, 2013 Fig. 3 – Left eye OCT showing CNVM in the nasal region of the macula with signs of exudative activity.
The utilization of intravitreal ranibizumab injections, extensively applied in approaches to macular degeneration and other diseases, was not broadly described in the scientific literature for CNVM associated to juxtapapillary CHR–RPE.
This treatment can counteract the progression of the lesion and avoids adding iatrogeny to the damages caused by the pathology itself. On the other hand, in some cases it is possible to combine different therapies such as vitrectomy
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
91
Fig. 4 – (A) Retinographs one month after the first intravitreal injection, showing activity of the lesion with initial cicatrization. (B) Retinographs one month after the second intravitreal injection, showing moderate reduction in the activity.
Fig. 5 – Retinographs one month after the third injection, showing lesion cicatrization, disappearance of hemorrhages and of serous detachment, with significant subregional residual fibrosis remaining.
92
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
OD
Macula thickness: Macular cube 512x128
OS
500 250 400
300
305 410
398 117 152
202
316 200 277 100 256
ILM-RPE Thickness (µm)
Fovea: fovea not found
0µm
Overlay: ILM-RPE transparency: 50% High-definition mode
ILM-RPE
N
T
ILM
Distribution of normals 99% 95% 5% 1% RPE S Central subfield Cube volume Cube average (mm3) thickness (µm) thickness (µm) I
ILM-RPE
117
9.5
264
Clinical history (anamnesis-current disease) Referred from Axarquia hospital for macular OCT, CNVM associated to LE optic nerve hamartoma, treated with 3 doses (latest Feb. 18, 2014). Supplementary tests: Macular OCT: highly arteracted with continuous blinking and inability to fix gaze, even with RE. RE: no significant changes from previous OCT. LE: Image compatible with subretinal fibrosis. Minimum amount of LSR (a lot less than previous OCT). Atrophic-degenerative changes, making it difficult to precisely determine degree of activity: although the impression is more like residuals, assess on basis of clinic and/or FAG activity. Málaga, May 19, 2014 Fig. 6 – New OCT which determined considerable deactivation of the neovascular lesion, with disappearance of liquid associated thereto. It also shows subretinal fibrosis and residual atrophic-degenerative changes.
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(2):87–93
or surgical approach of epiretinal membranes, when several CHR–RPE complications are associated in the same eye,9,10 even though and despite all the obstacles modest visual results can be obtained due to the severity of the sequels left by associated diseases.
Conflict of interest No conflict of interests has been declared by the authors.
5.
6.
7.
references
1. Badami A, Bianciotto CG, Shields C, Shields JA. Combined hamartoma of the retina and retinal pigment epithelium in a child with branchial cleft cysts. J Pediatr Ophthalmol Strabismus. 2012;49:e9–11. 2. Xue K, Mellington F, Gout I, Rokerya S, Olurin OI, El-Amir A. Combined hamartoma of the retina and retinal pigment epithelium. BMJ Case Rep. 2012;2012. S1757-790X. 3. Chang YC, Tsai RK. Coexistence of optic nerve head drusen and combined hamartoma of the retina and retinal pigment epithelium in a Taiwanese male. Kaohsiung J Med Sci. 2009;25:40–3. 4. Nowomiejska K, Zarnowski T, Rejdak R, Juenemann A. Combined hamartoma of the optic disc and retinal pigment
8.
9.
10.
93
epithelium – 3 years of the follow-up with semi-automated kinetic perimetry. Open J Ophthalmol. 2012;2:116–8. Nowomiejska K, Vonthein R, Patzold J, Krapp E, Rejdak R, Zarnowski T, et al. Comparison between semiautomated kinetic perimetry and conventional Goldmann manual kinetic perimetry in advanced visual field loss. Ophthalmology. 2005;112:343–54. Mateo C, Moreno JG, Lechuga M, Adán A, Corcóstegui B. Surgical removal of peripapillary choroidal neovascularization associated with optic nerve drusen. Retina. 2004;24:739–45. Pérez-Álvarez MJ, Escalada-Ferrándiz A, Hernández-García E, Moreno-López M, García Sánchez J. Hallazgos clínicos y tomográficos en el hamartoma combinado de retina y epitelio pigmentado retiniano: 2 casos. Studium Ophthalmologicum. 2009;XXVII:105–8. Cilliers H, Harper CA. Photodynamic therapy with verteporfin for vascular leakage from a combined hamartoma of the retina and retinal pigment epithelium. Clin Experiment Ophthalmol. 2006;34:186–8. Pérez-Álvarez MJ, Alejandre-Alba N, García-Sánchez J. Hamartoma combinado de retina y epitelio pigmentario retiniano. Diagnóstico mediante tomografía de coherencia óptica y angiofluoresceingrafía. Arch Soc Esp Oftalmol. 2008;83:193–6. Stallman JB. Visual improvement alter pars plana vitrectomy and membrane peeling for vitreoretinal traction associated with combined hamartoma of the retina and retinal pigment epithelium. Retina. 2002;22:101–4.