Idiopathic Peripapillary Subretinal Neovascular Membrane in a Young Woman with Recurrence of the Lesion during Pregnancy after Treatment with Intravitreal Bevacizumab.

We report a 27-year-old woman who was diagnosed with idiopathic peripapillary subretinal neovascular membrane (PSRNVM) in her left eye with best-corrected visual acuity (BCVA) of 20/160. She had been treated by three monthly doses of intravitreal bevacizumab (1.25 mg/0.05 ml) at 4-week intervals, which showed a favorable response. The treatment led to regression of the choroidal neovascular membrane (CNVM) with complete resorption of subretinal fluid and improvement of BCVA to 20/25. Subsequently, recurrence of the CNVM was observed during pregnancy (28 months after treatment). To the best of our knowledge, this is the first report of recurrence of idiopathic PSRNVM during pregnancy.

INTRODUCTION

Peripapillary subretinal neovascular membrane (PSRNVM) was first described by Lopez and Green.1 It is defined as a collection of new choroidal blood vessels within one disc diameter of the optic nerve head.2 PSRNVM accounts for 10% of all choroidal neovascular membranes (CNVMs) with a female predilection.3 The natural history of this type of CNVM is variable, since they can remain stable or produce severe central visual loss if the membrane extends to the macula, or through exudation and hemorrhage.4

It has been reported to be associated with several ocular conditions including age-related macular degeneration (AMD), multifocal choroiditis, angioid streaks, presumed ocular histoplasmosis (POHS), punctate inner choroidopathy, traumatic choroidal rupture, choroidal osteoma, optic disc drusen, congenital disc anomaly, and sarcoid. However, a minority of patients may develop PSRNVM without apparent cause and are grouped as a distinct entity called idiopathic PSRNVM.5

Several treatment modalities like surgical removal of the CNVM, photocoagulation, and photodynamic therapy (PDT) have been tried with varying success. Recently, encouraging results have been reported in case reports and small case series for managing PSRNVM with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.2

In this report, we discussed our experience in treating this condition, and the possiblity of the true association between pregnancy and recurrence of CNVM.

CASE REPORT

A 27-year-old woman who was referred to our retina service at Dhahran Eye Specialist Hospital; a tertiary referral ophthalmic hospital in the Eastern province of Saudi Arabia (in February 2010) with PSRNVM in the left eye complaining of painless worsening vision over the past month. She was otherwise healthy with no history of trauma.

On initial ophthalmic examination, the patient's best-corrected visual acuity (BCVA) was 20/20 in the right eye and 20/160 in the left eye. Pupils were equal, reactive and with no afferent pupillary defect. Applanation tonometry revealed intraocular pressure of 15 mm Hg in both eyes. Slit lamp examination of the anterior segment was unremarkable. There were no signs of the anterior chamber or vitreous inflammation. Fundoscopy was notable for scarred peripapillary temporal CNVM in the right eye and active PSRNVM in the left eye without predisposing fundus findings. Fluorescein angiography and optical coherence tomography (OCT) confirmed our diagnosis.

Initial screening tests to rule out possible inflammatory and infectious etiologies were unremarkable and included complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, Mantoux test, angiotensin-converting enzyme, treponema pallidum hemagglutination test, venereal disease research laboratory test, rapid plasma reagin, and toxoplasma (IgM, IgG) antibodies.

Three monthly doses of intravitreal bevacizumab (IVB) injections (1.25 mg/0.05 ml) at 4-week intervals were given after being discussed with and accepted by the patient, which led to regression of the CNVM with complete resorption of subretinal fluid (SRF) and improvement of BCVA to 20/25. No recurrence of the CNVM could be observed, with no further treatment needed during a 28-month follow-up.

Subsequently, the patient came back in October 2012 complaining of a sudden deterioration of vision in the same eye during the first trimester of pregnancy. Her BCVA was 20/20 in the right eye and 20/40 in the left eye. Slit lamp examination of the anterior and posterior segments was unremarkable except for the previously documented peripapillary temporal scarred CNVM in the right eye and a larger yellowish-grey peripapillary subretinal scar in the left eye [Figure 1a and b]. OCT revealed SRF within the papillomacular bundle extending to the macula of the left eye [Figure 2]. Fluorescein angiography showed an early hyperfluorescence in the peripapillary area of the right eye that stained in the late photos, but leakage was appreciated in the left eye [Figure 3a and b]. These findings found to be consistent with recurrence of the PSRNVM in the left eye. As the patient BCVA was minimally decreased, no intervention and frequent follow-ups were recommended.

Figure 1

Color fundus photograph taken when the patient came with recurrence of the peripapillary subretinal neovascular membrane showing: (a) Peripapillary temporal subretinal fibrous scarring in the right eye. (b) A larger peripapillary subretinal scar with active choroidal neovascular membrane in the left eye

Figure 2

Optical coherence tomography of the left eye showing: Recurrence of the peripapillary subretinal neovascular membrane with subretinal fluid and retinal thickening

Figure 3

Fluorescein angiography (late phase) taken when the patient came with recurrence of the peripapillary subretinal neovascular membrane (PSRNVM) demonstrates: (a) Hyperfluorescence due to staining of peripapillary subretinal fibrous scar in the right eye. (b) Leakage suggestive of recurrence of the PSRNVM in the left eye

Three months after an uneventful labor, the patient BCVA and OCT findings showed no improvement. Therefore, three injections of IVB (1.25 mg/0.05 ml) 4 weeks apart were given. One month after the third injection, the BCVA improved to 20/25 and the SRF resorbed [Figure 4] with no further recurrence observed till the last visit (a 6-month follow-up).

Figure 4

Optical coherence tomography of the left eye showing: Regression of the membrane and resorption of the subretinal fluid after three injections of intravitreal bevacizumab

DISCUSSION

Numerous ocular conditions can be influenced by pregnancy. The possible association of the development or recurrence of CNVM with pregnancy has not been confirmed. The significant hormonal changes, physiological alterations in cardiac output and hemodynamic parameters, and the increase in blood volume with excess angiogenic factors such as VEGF and placental growth factor (PGF) in normal pregnancy may affect the retinal pigment epithelium and choriocapillaris and potentially increase the risk of developing choroidal neovascularization.6

Peripapillary subretinal neovascular membrane represents an uncommon type of neovascularization that can be associated with several ocular diseases or may develop without an apparent cause and called (idiopathic).5 The diagnosis of PSRNVM in our case was classified as idiopathic in view of absence of a choroidal or retinal pigment epithelial disease process that may be associated with a CNVM in a young woman with no significant past medical history. Fluorescein angiography and OCT confirmed our clinical diagnosis. Indocyanine green (ICG) angiography may be a useful adjunct for the distinction of PSRNVM from other diagnoses having a similar clinical presentation, particularly polypoidal choroidal vasculopathy. Furthermore, it can provide images of CNVM through blood or serous fluid with better delineation of occult CNVM. However, the role of ICG in the evaluation of the clinical characteristics of CNVM is now much less important since the introduction of anti-VEGF treatment.7 Although there are two reports of idiopathic PSRNVM developing initially during pregnancy,68 recurrences in pregnancy have not been reported. This is the first report of idiopathic PSRNVM recurrence during pregnancy.

In some instances, this type of CNVM can be watched because of the asymptomatic nature, and treatment should be considered when the macula is threatened2 as in our case. Treatment options have included laser photocoagulation,9 subretinal surgery,10 and PDT.11 More recently, the use of anti-VEGF therapy has emerged as the optimal treatment for macular CNVM due to AMD, POHS, myopia, angioid streaks, and traumatic choroidal rupture.15 However, the information regarding the efficacy of anti-VEGF on PSRNVM is based on case reports and small case series that used either bevacizumab or ranibizumab for PSRNVM of various etiologies (high myopia,12 inflammatory,13 AMD,141516 angioid streaks,1416 idiopathic,1416 and sarcoidosis17). Overall the results suggest a possible beneficial effect of anti-VEGF on PSRNVM, but the long-term effect of the treatment is still uncertain.

In our patient, CNVM had already scarred in one eye and was active in the other eye when she presented to us. She was given a series of three injections of IVB (1.25 mg/0.05 ml) at 4-week intervals. The treatment led to regression of the CNVM with improvement of BCVA from 20/160 to 20/25. No further therapy was needed during a 28-month follow-up. Subsequently, recurrence of the CNVM in the left eye was observed during pregnancy and the BCVA declined to 20/40. As the patient BCVA was minimally decreased, the decision of observation with frequent follow-ups was made due to the possible theoretical teratogenic and fetotoxic effects of the limited therapeutic options. Three months after an uneventful labor, the patient was given the same regimen of treatment and responded favorably with no recurrences observed till the last visit (a 6-month follow-up).

CONCLUSIONS

It is possible that increased VEGF and PGF levels during pregnancy may play a role in the development or recurrence of CNVM. However, this association could be coincidental, and need to be investigated experimentally.

The results of our report and the previous published reports suggest a possible beneficial effect of anti-VEGF on PSRNVM. Further randomized or large studies are needed in order to determine the true usefulness and the long-term effect of anti-VEGF in the treatment of PSRNVM and to compare the established treatments in a controlled and standardized setting.