Long-term Resolution of Blinding Polypoidal Choroidal Vasculopathy with Recurrent Bilateral Central Involvement by Low-dose Oral Eplerenone Treatment.

A 55-year-old male presented with serous retinal detachment over 3 months in his right eye. His left eye was blind due to retinal pigment epithelium detachment since 1997 with atrophy of the neurosensory retina. Fluorescein angiography had previously shown bilateral polypoidal choroidal vasculopathy (PCV). Optical coherence tomography (OCT) confirmed PCV with central involvement. The patient underwent intravitreal injections of 6x Lucentis, 4x Avastin and one injection of aflibercept. PCV recurred from 1 to 4 months after each treatment. The patient had history of stroke, hypertension, and atrial fibrillation and was started on oral eplerenone 25 mg/day in October 2014, which resulted in a long-term ongoing complete retinal reattachment. OCT ganglion cell and inner plexiform layers showed full recovery of the fovea in the right eye and irreversible in the left eye. Low-dose eplerenone may resolve recalcitrant PCV with central involvement. The duration of treatment remains uncertain.

INTRODUCTION

The natural history of polypoidal choroidal vasculopathy (PCV) is variable and may be benign or result in permanent visual morbidity.1 Treatment of PCV is indicated if their central involvement, particularly if one eye has lost perception of color vision. Current treatment modalities include vascular endothelial growth factor (VEGF) blockers and photodynamic therapy, which may result in temporary or long-term cure of polyps and subretinal fluid accumulation but also have moderate to high rate of recurrences.2 Surgery with vitrectomy and r-tPA has been implicated in submacular hemorrhage, which is uncommon.3

Recently, eplerenone has been reported as a successful medical treatment including long-term prevention of recurrence of PCV.4 Experimental data lend a scientific basis to this approach.56 We report a patient with PCV with central involvement who was successfully treated with eplerenone.

CASE REPORT

A 55-year-old male patient working as an offshore engineer presented in November 2012 with a history of recent metamorphopsias and reduced vision in his previously unaffected right eye. The left eye had a persistent central serous retinopathy since 1997, which had been treated with laser and photodynamic therapy repeatedly without success. Fluorescein angiography indicated later PCV. However, he experienced a serious allergic reaction to fluorescein angiography.

At presentation on November 2012, best spectacle-corrected visual acuity (BSCVA) was 0.8 (decimal notation) with −0.25 D in the right eye with a relative central scotoma. BSCVA in the left eye was 0.1 (decimal notation) with +1.25-1.25 × 75°. Color vision was normal in the right eye but almost completely lost in the left eye (Ishihara charts 1/38).

Slit lamp examination indicated incipient cortical cataracts, posterior vitreous detachments, and normal optic discs with cup-to-disk ratios of 0.3 bilaterally. The central retinal thickness was increased bilaterally. The macula was not well demarcated in both eyes. The left eye showed atrophy of the retinal pigment epithelium and subretinal lipid deposits. Pachymetry-corrected intraocular pressure was 12 mmHg in both eyes.

Optical coherence tomography (OCT) showed extensive central detachments of the neurosensory retina and grossly enlarged “polypoid” subretinal vessels, OS > OD. One polypoidal vessel in the right eye was very close to the papillomacular nerve fiber bundle. Average retinal ganglion cell layer (GCL) and macular inner plexiform layer (IPL) thickness were markedly decreased in the acutely affected right eye and mildly decreased in the left eye [Figure 1a–c]. OCT papillometry showed normal anatomical results bilaterally. Fluorescein angiography was contraindicated due to the previous allergic reaction.

Figure 1

(a) Optical coherence tomography of the macula shows an acute serous retinal detachment (retinal thickness 529 my) in the previously healthy right eye of a 55-year-old male prediagnosed with bilateral polypoidal choroidal vasculopathy. In the retinal pigment epithelium slice, four paramacular elevations reveal subretinal polypoidal vessels. Visual acuity: OD 1.0 (decimal notation) OS 0.16 (decimal notation). (b) The left eye of the patient from a showing residual paramacular serous retinal detachment of the neurosensory retina after multiple laser and photodynamic treatment. In the retinal pigment epithelium slice, a large paramacular sacculated subretinal polypoidal vessel close to the fovea and many smaller juxta macular subretinal polyps can be identified. (c) Optical coherence tomography with ganglion cell and inner plexiform layer analysis shows reduction in both eyes indicating ischemic changes in the foveal avascular zone. (d) Three weeks after injection of aflibercept (6 weeks after recurrence of central serous retinal detachment) in the right eye residual submacular fluid is still present. Aflibercept did not seem effective in this case compared to ranibizumab or bevacizumab. (e) Three weeks after injection of aflibercept in the right eye submacular fluid is still present in the left eye. Aflibercept did not seem effective in this case compared to ranibizumab or bevacizumab. (f) In the optical coherence tomography with ganglion cell and inner plexiform layer analysis, no significant resolution of the ischemic foveolar avascular zone can be visualized neither in the injected nor the left fellow eye

Systemic history included a stroke in 2007 due to untreated hypertension and atrial fibrillation. Systemic medications at presentation were simvastatin 20 mg/day for a mixed hyperlipidemia and dabigatran etexilate 220 mg/day for prevention of thromboembolism. As the patient was free from atrial fibrillation since 2008 (Holter negative), he was advised to discontinue dabigatran and continue low-dose aspirin (100 mg/day). His blood pressure at presentation was 140/70 mmHg, pulse rate 70/s. The blood pressure measurements were unstable as repeat measurements showed values up to 175/95 mmHg. ECG was abnormal with ventricular premature complexes (short R-R, aberrant QRS), and echocardiography showed Grade I left ventricular diastolic dysfunction [Figure 2f].

Figure 2

(a) An acute recurrence <5 weeks after the injection of aflibercept can be seen in the right eye (macular thickness 518 μm). At this time, oral eplerenone 25 mg/day was initiated and resulted in a significant decrease of retinal thickness of − 28 μm after 1 week. (b) The trend from a continued over the next week (498 μm = −20 μm), and 1 month after starting the patient on eplerenone, the subretinal fluid in the right eye was almost completely absorbed (macular thickness 301 μm = −217 μm) except for a paracentral residual (353 μm). (c) The trend from Figures 2a and b continued until all subretinal fluid was absorbed (central macular thickness 226 μm, paracentral retinal thickness 325 μm), a finding, which is continuing. (d) Parallel to the resolution of subretinal fluid accumulation in the right eye the left eye shows complete absorption of the subretinal fluid and a reduction of macular thickness from 205 to 182 μm. (e) The optical coherence tomography ganglion cell and inner plexiform layer analysis show a significant increase in the right eye demonstrating the recovery of the ischemic fovea. In the left eye, no significant resolution of the ischemic foveolar avascular zone can be visualized. The intermittent short-lived improvements since 1997 did not prevent the damage of the foveolar avascular zone. (f) The electrocardiogram of the patient with a history of stroke in 2007 due to untreated hypertension and atrial fibrillation shows ventricular premature complexes (short R-R, aberrant QRS), and echocardiography showed Grade I left ventricular diastolic dysfunction

This functionally monocular patient with polyps in the papillomacular bundle received 0.5 mg injections of intravitreal ranibizumab (on an “as needed” schedule) in his right eye on November 28, 2012, and March 25, 2013, with complete reattachment. At the next visit on March 11, 2014, he reported recurrences necessitating four injections of intravitreal bevacizumab in the right eye in his country of residence with even shorter symptom-free intervals. He received another four ranibizumab injections on March 19, 2014; April 16, 2014; May 28, 2014; and August 27, 2014, along with focal laser treatment. Following every injection, the retina in the right eye was completely reattached after a maximum of 2 weeks. Despite complete reattachments of the retina, recurrences appeared within 1-4 months. After the first and fourth injections, the left retina was reattached. While the GCL + IPL values recovered completely in the right eye, the left eye had permanent loss despite complete retinal reattachment. When the retina was reattached, the BSCVA in the left eye did not increase beyond 0.16.

To achieve longer recurrence-free intervals, the patient received intravitreal aflibercept (2 mg) October 5, 2014. Up to 3 weeks after injection, aflibercept did not result in retinal reattachment of both eyes [Figure 1d and e]. At this time, the macular GCL and IPLs (GCL + IPL) were markedly decreased in both eyes [Figure 1f]. A phase of fast increase of subretinal fluid [Figure 2a] necessitated a decision on how to proceed further. The patient was reluctant to undergo photodynamic therapy that had resulted in visual impairment of the left eye.

Eplerenone, which has been reported to be effective in central serous retinopathy, was indicated from both ophthalmological and cardiological standpoints. Standard initial low-dosage oral eplerenone at 25 mg/day was started. After 2 weeks, the retina was completely reattached in both eyes [Figure 2b–d]. The macular GCL and IPL (GCL + IPL) recovered to normal thickness, but in the left eye, the reduction persisted in accordance with long-standing damage to the foveal avascular zone [Figure 2e]. To date, the patient has not experienced any further recurrences and remains on the low-dose regimen of eplerenone. BSCVA in the right eye was 1.0 with −0.25 D and 0.16 with +1.25-1.25 × 75° in the left eye. There was no relative scotoma in the right eye, and the color vision was normal in the right eye (Ishihara 38).

DISCUSSION

In this case report, we presented a functionally monocular patient with atrial fibrillation and bilateral PCV recalcitrant to VEGF blocker and laser treatment. PCV had central involvement, and oral eplerenone treatment was a successful alternate treatment for this patient.

Currently, the preferred treatment for PCV with central involvement is invasive and/or destructive using intravitreal VEGF blockers,78 surgery,3 and thermodestructive methods (laser, photodynamic treatment).9 As PCV is frequent in the Middle East and on the Indian subcontinent, noninvasive medical treatments may be preferable.

In our case, the patient suffered from hypertension and previous atrial fibrillation, a condition which facilitated the decision for the potassium sparing aldosterone-antagonist eplerenone treatment. Future studies should investigate the risk profile (incidence of symptomatic hyperkalemia) of low-dose eplerenone for PCV with central retinal involvement before routine applications by ophthalmologists in both hypertensive and nonhypertensive patients can be recommended. Classical central serous retinopathy has been shown to be responsive to this treatment,4 but the recurrence rate of this condition without PCV is generally much lower. In the current case, we cannot determine if discontinuation of eplerenone will result in a recurrence. As the treated eye is the only seeing eye, we opted for a long-term treatment.

Macular GCL and IPL (GCL + IPL) measurements were a helpful multimodal imaging addition in showing ischemic damage to the fovea and indicating treatment for reattachment of the central retina. It also showed that the intermittent short-lived improvements over the years since 1997 did not prevent the permanent damage of the foveolar avascular zone in the left eye.

PCV is a bilateral, common condition. Although central involvement is mostly unilateral, there is a potential risk of bilateral blindness.1 In our case report, color blindness and low vision were complications of long-standing PCV with central retinal involvement and emerging nondestructive treatment options with systemic mineralocorticoid antagonists seem to be more effective than the treatment with VEGF blockers alone.

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Conflicts of interest

There are no conflicts of interest.