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NR 1-3/2009
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Atypical
peripapillary location of choroidal neovascularization – cases
report
Nietypowa przytarczowa
lokalizacja neowaskularyzacji podsiatkówkowej – opis przypadków
Figurska Małgorzata, Wierzbowska Joanna
From the Clinic of Ophthalmology of the Military Institute of
Medicine in Warsaw
Head: Professor Stankiewicz Andrzej, MD, PhD (2nd degree) |
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| Summary: |
Choroidal
neovascularization (CNV) is one of the main reasons for
sight loss in adults. CNV located at the border of the
optic disc or adherent atrophy is described as
peripapillary choroidal neovascularisation (PPCNV).
The aim of the work is to present a course of changes
and the effects of treatment with intravitreal
ranibizumab injections for peripapillary subretinal
neovascularization, its consequences and accompanying
other CNV foci in two patients. The diagnosis and
monitoring of the therapeutic effects were based on the
results of fluorescein angiography and OCT. In a
53-year-old female patient three injections of
ranibizumab at a dose of 0.05 mg were administered
according to a saturation regimen. Visual improvement of
5 lines on an ETDRS board (25 letters) was obtained, as
well as withdrawal of the subretinal fluid from the area
of the macula in OCT and limitation of the peripapillary
exudate visible in 12 months follow-up angiography. In a
70-year-old female patient bilateral development of
symmetric peripapillary CNV foci was observed
accompanied by a occult CNV focus in the left eye macula.
Spontaneous CNV limitation without macular lesions was
visible in the right eye. Intravitreal ranibizumab
injections were given into the left eye. A 12 months
follow-up revealed vision stabilisation in both eyes at
the baseline level.
Conclusions: Intravitreal injections can be used in the
treatment of atypical extramacular CNV, responsible for
secondary damage to the fovea. Ranibizumab, a
non-selective VEGF-A inhibitor, allows the elimination
of changes in the central retina, closure or significant
limitation of the exudates and vision improvement.
Spontaneous limitation of lesions may also be frequently
expected in the eyes with peripapillary CNV foci. |
| Słowa kluczowe: |
peripapillary choroidal
neovascularization, intravitreal injections, ranibizumab. |
| Key words: |
przytarczowa
odnaczyniówkowa neowaskularyzacja, iniekcje
doszklistkowe, ranibizumab. |
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Choroidal neovascularization (CNV)
is one of the main reasons for sight loss in adults. CNV located
at the border of the optic disc or adherent atrophy is described
as peripapillary choroidal neovascularization (PPCNV). Changes
of this type are usually classified as extrafoveal CNV foci.
Clinical trials have demonstrated that in the majority of cases
this is occult CNV (1). A natural history of PPCNV is various:
starting from stable, asymptomatic foci found in an
ophthalmoscopic examination to conditions of a progressive
course, where CNV is located in the papillo-macular bundle,
fovea, and is accompanied by haemorrhages and exudates as well
as progressive vision impairment (2).
The aim of the work is to present a course of changes and the
effects of treatment with intravitreal injections of ranibizumab
(Lucentis) for peripapillary subretinal neovascularization, its
consequences and other accompanying CNV foci in two patients
during 12 months follow-up.
Case 1.
A 53-year-old female patient reported herself at the Retinal
Clinic due to visual acuity impairment in the left eye lasting
for 4 months and blurring in the centre of the field of vision
and image distortion. A full ophthalmic examination was
performed, together with the visual acuity evaluation using
Snellen and ETDRS charts (Vod 0.80 sc – 82 letters), Vos 0.10 sc
– 36 letters), the evaluation of the anterior and posterior
segment using a slit lamp, retinoscopy, aplanation tonometry,
ultrasound examination, fluorescein angiography and OCT (SOCT
Copernicus). Drusen typical of dry degenerative lesions were
observed in the macula in the fundus of the right eye. In the
left eye at the superior and temporal edge of the optic disc a
greyish, elevated lesion with border exudates was visible, and a
focus of the subretinal fluid with a round border in the macula.
Fluorescein angiography (FA) of the right eye revealed retinal
pigment epithelial window defects typical of drusen. In the left
eye at the optic disc FA revealed hyperfluorescence increasing
in time, typical of CNV with fluorescein retention in later
study phases in accompanying fluid compartments in the
papillo-macular bundle and in the macula (Fig. 1). OCT of the
right eye revealed wavy distortion of the reflection line from
the pigment epithelium layer confirming the presence of drusen.
OCT of the left eye above the optic disc revealed the subretinal
fluid and retinal oedema (Fig. 2). The subretinal fluid was also
visible in foveal tomograms (Fig. 3). A decision was made to
administer ranibizumab at a dose of 0.5 mg in a saturation
regimen into the vitreous body – three doses at one month
intervals. As early as after the first injection vision
improvement in the left eye up to 56 letters – 0.25 on an
ETDRS chart was observed what correlated with a complete removal
of the subretinal fluid visible in macular tomograms and with
restoration of a foveal contour (Fig. 4). Above the optic disc
in the left eye OCT revealed the retention of the subretinal
fluid and retinal oedema (Fig. 5). FA of the left eye performed
one month after the injection of Lucentis revealed a complete
withdrawal of fluid from the macula and the papillo-macular
bundle and a significant limitation of the exudates above the
optic disc (Fig. 6). In a 12 months follow-up we do not observe
recurrence of the subretinal fluid into the foveal area and the
foveal retina is 113 µm thick (Fig. 7). The visual acuity in the
left eye is stable and maintained at the level of 0.32 (61
letter ETDRS) what constitutes the improvement of 25 letters
when compared to the baseline. Follow-up fluorescein angiography
revealed persistent but limited exudates typical of occult CNV
above the optic disc in the left eye (Fig. 8) what correlates
with the presence of persistent fluid and a distorted reflection
line from the RPE/choriocapillaries in OCT (Fig. 9). The patient
is still being monitored. The visual acuity and the OCT image
are checked every 5-6 weeks.
Case 2.
A 70-year-old female patient was referred to the Retinal Clinic
with suspected central retinal vein thrombosis in the right eye
with the aim of further diagnostics. She did not report visual
acuity impairment in her medical history. A full ophthalmic
examination was performed, together with the visual acuity
evaluation using Snellen and ETDRS charts (Vod 1.00 cc +4.0 Dsph
– 84 letters, Vos 0.80 cc +4.5 Dsph – 79 letters), the
evaluation of the anterior and posterior segment using a slit
lamp, retinoscopy, aplanation tonometry, ultrasound examination,
fluorescein angiography and OCT (SOCT Copernicus). The
ophthalmoscopic examination revealed oedema and a greyish
elevated lesion with subretinal haemorrhage at the nasal edge of
the optic disc in the right eye. Fluorescein angiography of the
right eye revealed a peripapillary focus of increasing
hyperfluorescence typical of CNV, surrounded by constant
hypofluorescence – blockage of fluorescence by blood (Fig. 10).
The right eye macula was normal on FA. Heterogeneous
hyperfluorescence was visible in the left eye macula on FA (Fig.
11). In OCT of the right eye macular tomograms did not
demonstrate abnormalities; the retinal foveal thickness was 153
µm (Fig. 12). OCT of the left eye revealed some unexpected
subfoveal fluid and a distorted reflection line from the RPE/
choriocapillaries as in occult CNV (Fig. 13). Moreover, NMR CNS
was performed in order to eliminate possible optic disc oedema
associated with increased intracranial pressure. As OCT of the
right eye macula did not reveal abnormalities and the visual
acuity was good, the decision was made to observe a
peripapillary CNV focus and blood vessel-tightening agents were
recommended. The left eye was qualified for treatment with
intravitreal ranibizumab injections at a dose of 0.5 mg.
Following two injections we observed withdrawal of the subfoveal
fluid and restoration of a foveal contour (Fig. 14). During
subsequent follow-up FA a fresh CNV focus with haemorrhages,
symmetrical to the right eye appeared at the nasal edge of the
optic disc (Fig. 15). A subsequent, third injection of
ranibizumab into the left eye was performed. Six weeks later OCT
of the left eye macula did not reveal abnormalities, a
peripapillary CNV focus stabilised and haemorrhages partly
absorbed. In addition, laser barrage on the CNV border at the
right eye optic disc was conducted. The fundus of both eyes are
monitored. We observe stabilisation of the macular areas in OCT
and visual acuity at the baseline level. The ophthalmoscopic
examination reveals scarring of the peripapillary foci.
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Discussion
Peripapillary subretinal choroidal neovascularization may
accompany different optic disc abnormalities such as drusen, pit,
slit or oedema. It can be observed in myopic eyes, with angioid
streaks, ocular histoplasmosis, following traumas, uveitis, in
evanescent white-dot syndrome, with peripapillary choroidal
naevus, with the inflammation of the intermediary part of the
vitreous body or in the course of sarcoidosis. According to
Browning et al. PPCNV most commonly occurs in the course of
age-related maculopathy (45%), as idiopathic disease (39%), in
the course of multifocal retinochoroidal inflammation (2.6%),
ocular histoplasmosis (1.7%), choroidal osteoma (0.9%) or drusen
in the optic disc (0.9%) (3). PPCNV etiopathogenesis is
suspected to be associated with peripapillary defects in the
Bruch’s membrane resulting in choroidal neoplasia. Usually the
course of PPCNV is slow, asymptomatic until secondary macular
changes develop (4). In the material discussed in our report
both cases were associated with additional AMD-like degenerative
lesions in the foveas of other eyes, and a occult CNV focus
appeared in the macula in the second case. In the other eye
peripapillary CNV occurs in 20% of patients during 2-year
follow-up (3). In our report it developed within a few months in
the second case. One of the methods to treat PPCNV is laser
ablation of an active lesion and protection of its boundaries.
Browning et al. reported CNV relapses in about 20% of patients
following laser ablation. Similar relapse rates are demonstrated
by Cialdini et al. – between 20 and 28% cases (5). Protective
laser coagulation at the border of peripapillary
neovascularization was performed in the case of the second
patient (right eye).
Another method to treat PPCNV is photodynamic therapy (PDT) with
Visudyne. Rosenblatt et al. applied PDT in the eyes with PPCNV,
with the following parameters observed: a laser focus at the
distance of at least 125 μm from the optic disc edge, duration
of a diode laser action 30 seconds, a light energy dose of 18
J/cm² (6). No defects in the nerve fibre layer were found;
vision improvement and the resolution of subretinal exudates and
haemorrhages accompanying CNV were seen.
There is also a report on surgical removal of vast PPCNV lesions
using pars plana vitrectomy with retinotomy. Kokame et al.
presented the results of such proceedings in six patients with
vast lesions with secondary foveal involvement (7). Vision
improved or stabilised in 85% of cases and in one patient a CNV
relapse occurred within one month which was effectively treated
with laser therapy, and a late relapse 3 years post-procedure
was observed in two patients. Harshivinderjit et al. do not
demonstrate such good effects in a group of 17 patients with
vast PPCNV, who underwent surgical treatment (8). Vision
stabilisation or improvement was observed in less than half of
patients.
As laser therapy, photodynamic therapy or vitreoretinal therapy
are not always associated with positive effects of PPCNV
treatment, it seems reasonable to use other methods, such as
intravitreal injections of VEGF-A inhibitors. In the reported
cases pathological processes were limited following intravitreal
injections of ranibizumab.
Conclusions
1. Therapy with intravitreal injections of ranibizumab is used
to manage atypical, extramacular CNV lesions, which cause
secondary foveal damage.
2. Ranibizumab, a non-selective VEGF-A blocker, helps to
withdraw lesions in the central retina, to close or limit
significantly a primary peripapillary exudates and allows vision
improvement.
References:
1. Kies JC, Bird AC: Juxtapapillary choroidal neovascularization
in older patients. Am J Ophthalmol 1988, 105, 11-19.
2. Lopez PF, Green WR: Peripapillary subretinal
neovascularization, a review. Retina 1992, 12, 147-171.
3. Browning DJ, Fraser CM: Oculary condition associated with
peripapillary subretinal neovascularization, their relative
frequencies and associated outcomes. Ophthalmology 2005, 112
(6), 1054-1061.
4. Curcio CA, Saunders PL, Younger PW, Malek G: Peripapillary
chorioretinal atrophy: Bruch’s membrane changes and
photoreceptor loss. Ophthalmology 2000, 107, 334-343.
5. Cialdini AP, Jalkh AE, Trempe CL: Argon green laser treatment
of peripapillary choroidal neovascular membranes. Ophthalmic
Surg 1989, 20, 93-99.
6. Rosenblatt BJ, Shah GK, Blinder K: Photodynamic therapy with
verteporfin for peripapillary choroidal neovascularization.
Retina 2005, 25(1), 33-37.
7. Kokame GT, Yamamoka S: Subretinal surgery for peripapillary
subretinal neovascular membranes. Retina 2005, 25(5), 564-569.
8. Harshivinderjit SB, Patel MR, Harinderjit S, Marcus DM:
Surgical treatment of extensive peripapillary choroidal
neovascularization in ederly patients. Retina 2003, 23(4),
469-474.
The study was originally received 9.12.2008 (1088)/
Praca wpłynęła do Redakcji 9.12.2008 r. (1088)
Accepted for publication 20.01.2009/
Zakwalifikowano do druku 20.01.2009 r.Adres do
korespondencji (Reprint requests to):
Małgorzata Figurska, MD, PhD
Clinic of Ophthalmology Military Institute of Medicine
ul. Szaserów 128
00-909 Warszawa
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Fig. 1. Case 1. Baseline fluorescein
angiography of the left eye. At the optic disc increasing in
time hyperfluorescence typical of CNV with fluorescein retention
in later study phases in accompanying fluid compartments in the
papillo-macular bundle and the macula.
Ryc. 1. Przypadek 1. Wyjściowa angiografia fluoresceinowa oka
lewego. Przy tarczy nerwu wzrokowego narastająca w czasie
hiperfluorescencja typowa dla CNV z zastojem fluoresceiny
w późnych fazach badania w towarzyszących przestrzeniach
płynowych w pęczku plamkowo-tarczowym i w plamce.
Fig. 2. Case 1. Baseline OCT of the left eye.
Above the optic disc the subretinal fluid and retinal oedema.
Ryc. 2. Przypadek 1. Wyjściowe OCT oka lewego. Powyżej tarczy
nerwu II płyn podsiatkówkowy oraz obrzęk siatkówki.
Fig. 3. Case 1. Baseline OCT of the left eye –
macular tomograms. The subretinal fluid, a distorted foveal
contour.
Ryc. 3. Przypadek 1. Wyjściowe OCT oka lewego – tomogramy
plamkowe. Płyn podsiatkówkowy, zniekształcony kontur dołka.
Fig. 4. Case 1. OCT of the left eye following
the first intravitreal ranibizumab injection. Complete removal
of the subretinal fluid visible in macular tomograms and
restoration of a foveal contour.
Ryc. 4. Przypadek 1. OCT oka lewego po pierwszej iniekcji
doszklistkowej ranibizumabu. Całkowite wycofanie się płynu
podsiatkówkowego w tomogramach plamkowych i odtworzenie konturu
dołka ze zmniejszeniem grubości siatkówki dołeczkowej do 129 µm.
Fig. 5. Case 1. OCT of the left eye following
the first intravitreal ranibizumab injection. The amount of the
subretinal fluid has decreased above the optic disc, the retinal
oedema persists.
Ryc. 5. Przypadek 1. OCT oka lewego po pierwszej iniekcji
doszklistkowej ranibizumabu. Powyżej tarczy nerwu wzrokowego
zmniejszyła się ilość płynu podsiatkówkowego, utrzymuje się
obrzęk siatkówki.
Fig. 6. Case 1. Fluorescein angiography of the
left eye one month after the first injection. Complete removal
of the fluid in the macula and the papillo-macular bundle and a
significant limitation of the exudate above the optic disc.
Ryc. 6. Przypadek 1. Angiografia fluoresceinowa oka lewego
miesiąc po pierwszej iniekcji. Całkowite wycofanie się ognisk
płynowych w plamce i w pęczku plamkowo-tarczowym oraz znaczne
ograniczenie przecieku powyżej tarzcy nerwu II.
Fig. 7. Case 1. OCT of the left eye in 12
months follow-up. The recurrence of the subretinal fluid is not
observed, a foveal contour is maintained, the retinal foveal
thickness is 113 µm.
Ryc. 7. Przypadek 1. OCT oka lewego w obserwacji 12-miesięcznej.
Nie obserwuje się nawrotu płynu podsiatkówkowego, kontur dołka
zachowany, grubość siatkówki w dołeczku – 113 µm.
Fig. 8. Case 1. Fluorescein angiography of the
left eye in 12-month follow-up. A decreased exudate typical of
occult CNV persists above the optic disc.
Ryc. 8. Przypadek 1. Angiografia fluoresceinowa oka lewego w
obserwacji 12-miesięcznej. Powyżej tarczy nerwu II utrzymuje się
zmniejszony przeciek typowy dla ukrytej CNV.
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Fig. 9. Case 1. OCT of the left eye in
12-month follow-up. The subretinal fluid, a distorted reflection
line from the RPE/ choriocapillaries, retinal oedema persist
above the optic disc.
Ryc. 9. Przypadek 1. OCT oka lewego w obserwacji 12-miesięcznej.
Powyżej tarczy nerwu II utrzymuje się płyn podsiatkówkowy,
zniekształcony prążek odbić linii RPE/ choriokapilary, obrzęk
siatkówki.
Fig. 10. Case 2. Fluorescein angiography of
the right eye. A peripapillary focus of increasing
hyperfluorescence typical of CNV, surrounded by constant
hypofluorescence – fluorescence blockage by blood.
Ryc. 10. Przypadek 2. Angiografia fluoresceinowa oka prawego.
Przytarczowe ognisko narastającej hiperfluorescencji
charakterystycznej dla CNV otoczonej stałą hipofluorescencją –
blokada fluorescencji przez krew.
Fig. 11. Case 2. Fluorescein angiography of
the left eye. Heterogenous hyperfluorescence in the macula.
Ryc. 11. Przypadek 2. Angiografia fluoresceinowa oka lewego. W
plamce niejednorodna hiperfluorescencja.
Fig. 12. Case 2. OCT of the right eye. Normal
macular tomograms, retinal foveal thickness of 153 µm.
Ryc. 12. Przypadek 2. OCT oka prawego. Tomogramy plamkowe
prawidłowe, grubość siatkówki w dołeczku – 153 µm.
Fig. 13. Case 2. OCT of the left eye. The
subfoveal fluid, a distorted reflection line from RPE/
choriocapillaries – occult CNV.
Ryc. 13. Przypadek 2. OCT oka lewego. Płyn poddołkowy,
zniekształcony prążek odbić RPE/ choriokapilary – ukryta CNV.
Fig. 14. Case 2. The left eye – withdrawal of
the subfoveal fluid and restoration of a foveal contour
following two ranibizumab injections.
Ryc. 14. Przypadek 2. Oko lewe – wycofanie się płynu
poddołkowego i odtworzenie konturu dołka po dwóch iniekcjach
ranibizumabu.
Fig. 15. Case 2. The left eye – appearance of
a new focus of peripapillary CNV.
Ryc. 15. Przypadek 2. Oko lewe – pojawienie się nowego ogniska
przytarczowej CNV.
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