Case of the Month

Edited by Robert N. Johnson, MD

March, 2017

A 63-year-old female presents with decreased vision in both eyes.

Presented by Judy Chen, MD

Figure 1: Color photograph of the right eye showing a submacular hemorrhage with associated subretinal fluid, and hard exudates extending inferiorly.

Figure 2: Color photograph of the left eye showing orange-red discoloration of the macula with associated subretinal fluid.

Case History

A 63-year-old Asian female presents with a 1-month history of decreased vision in both eyes, right more than left.  Her past medical history was significant for a distant concussion with persistent hand tremors. Past ocular history, family history and review of systems were noncontributory.

On examination, her best-corrected visual acuity was 20/250 in the right eye and 20/40 in the left eye. Ocular motility, pupillary examination, intraocular pressure, and anterior segment examinations were normal in both eyes.  The posterior segment examination of the right eye revealed submacular hemorrhage and fluid with hard exudates extending inferiorly (Figure 1).  Dilated fundus examination of the left eye showed an orange-red discoloration of the macula with associated subretinal fluid (Figure 2).

Fluorescein angiography of the right eye demonstrated blockage from submacular hemorrhage and multiple areas of hyperfluorescence and leakage throughout the macula (Figure 3). Hyperfluorescence inferonasally in the macula of the left eye (Figure 4) was noted.  These areas of hyperfluorescence and leakage were most consistent with choroidal neovascularization.  Optical coherence tomography (OCT) scans of the right eye revealed significant subretinal hemorrhage with obliteration of the normal foveal contour and associated subretinal fluid in the right eye (Figure 5). OCT scans of the left macula exhibited a small subfoveal area of subretinal fluid with associated small pigment epithelial detachments (Figure 6).

Figure 3: Fluorescein angiogram of the right eye showing several areas of leakage as well as some blocked fluorescence due to the subretinal hemorrhage.

Figure 4: Fluorescein angiogram of the left eye showing sugfoveal dye leakage

Figure 5: Spectral domain OCT of the right eye showing a pigment epithelial detachment with subretinal hemorrhage and some macular edema. The chroidal vessels appear to be enlarged.

Figure 6: Spectral domain OCT of the left eye showing a serous detachment, and some RPE irregularity. Note the enlarged choroidal vessels in the macula.

What is your Diagnosis?

Differential Diagnosis

Neovascular age-related macular degeneration, central serous chorioretinopathy, pachychoroid neovasculopathy, pathologic myopia with neovascularization, polypoidal choroidal vasculopathy

 

Additional Case History

The patient has subsequently received over twenty intravitreal injections of bevacizumab in both eyes, with improvement of visual acuity to 20/32 in the right eye and 20/25 in the left.  Indocyanine green angiography performed on follow-up showed a branching network of inner choroidal vessels with nodular polypoidal aneurysms in both eyes, as well as a single focal area of hyperfluorescence in late frames in the left eye (Figures 7 and 8).  OCT angiography revealed persistently perfused choroidal neovascular membranes in both eyes (Figures 9 and 10), justifying continued anti-vascular endothelial growth factor (VEGF) treatment.

Figure 7: Indocyanine green angiography of the right eye reveals a branching network of inner choroidal vessels with nodular polypoidal aneurysms in the right eye

Figure 8: : Indocyanine green angiography of the left eye shows similar branching network of choroidal vessels as well as a single focal area of hyperfluorescence in late frames.

Figure 9: OCT angiography of the right macula shows perfused choroidal neovascularization.

Figure 10: OCT angiography of the left macula shows perfused choroidal neovascularization.

Discussion

Polypoidal choroidal vasculopathy (PCV) is a bilateral, exudative, hemorrhagic maculopathy, which is a variant of type 1 neovascularization and a subtype of age-related macular degeneration.  First reported by Yannuzzi et al in 1982 at the American Academy of Ophthalmology Annual Meeting, it was described as a peculiar hemorrhagic disorder involving the macula characterized by recurrent subretinal pigment epithelial bleeding.1 The prevalence of PCV in the United States is 7.8%,2 and while the average age of diagnosis is 68.4 years, it has been reported in patients from 21-93 years of age.3 PCV is also significantly more common in non-Caucasian populations, particularly Asian, Hispanic, and African-American patients.2

The pathogenesis is still incompletely understood, but is believed to stem from a primary abnormality of the choroidal circulation.  The disease is characterized by the presence of a network of inner choroidal vessels with aneurysmal, polyp-like, bulb-shaped endings.2 Histopathologic examination has revealed dilation and degeneration of the wall of large venules, degeneration of small arterioles, and capillaries with thickened basement membranes.4 Systemic hypertension, elevated C-reactive protein, atherosclerosis, cigarette smoking, and a history of central serous chorioretinopathy have all been reported as risk factors for the development of PCV.2.3 More recently, polymorphisms in the HTRA1 gene and complement factor H variants rs3753394 and rs800292 have been found to be significantly associated with PCV.5

 Polypoidal choroidal vasculopathy is characterized by orange-red elevated lesions of the posterior segment, associated with variably sized serous and serosanguineous detachments of the retina and retinal pigment epithelium.3,5 The lesions are most commonly located in the posterior pole but can extend to the peripheral fundus and may be associated with vitreous hemorrhage, subretinal fibrinous material, hard exudates, drusen, pigment epithelial hyperplasia, and atrophy. Patients with acute lesions typically present with widespread subretinal hemorrhage with minimal macular edema and relatively good vision.5 Indocyanine green angiography (ICGA) is the study of choice for imaging choroidal vascular abnormalities since its increased transmittance allows for better resolution of the choroid and its longer wavelength increases its penetrance, which is particularly useful in the presence of hemorrhage.  Fluorescein angiography is of limited use in these cases due to blockage from pigment and hemorrhage in the fundus.  Ocular coherence tomography (OCT) imaging will show dilated Haller layer vessels, known as pachyvessels, under the site of neovascular growth, with associated attenuation of the choriocapillaris and Sattler layers.6 OCT angiography allows for direct visualization of anomalous choroidal vasculature, which may be useful in monitoring the efficacy of treatments.

The mainstays of treatment for PCV include laser photocoagulation, photodynamic therapy (PDT), anti-VEGF injections, or a combination of these.  Resistance to anti-VEGF treatment is common in patients with PCV. Laser photocoagulation can be an effective choice in extrafoveal lesions.   Photodynamic therapy is the preferred treatment, with 80% of patients with preservation or improvement of vision at one year.5 PDT is also theoretically advantageous due to direct targeting of choroidal lesions rather than incurring retinal damage as thermal laser does.  However, while PDT has been shown to reduce the size of polypoidal vessels, it may not eliminate them completely and can be complicated by massive subretinal hemorrhage.  OCTA imaging of a patient with PCV treated with PDT shows occlusion of choroidal vessels on post-procedure day 7 (Figure 11B), but with partial reperfusion at month 5 (Figure 11C).  Intravitreal injections of anti-VEGF agents have been attempted with mixed success.  The EVEREST study found that while patients treated with ranibizumab alone achieved similar gains in visual acuity and similar reductions in central retinal thickness, the PDT and PDT + ranibizumab groups had a statistically significantly higher proportion of patients (75%) with complete regression of polyps at Month 6, compared to ranibizumab alone (33%).7 Sub-tenons injections of triamcinolone acetonide and pars plana vitrectomy have also been reported in the treatment of PCV.

Figures 11A-C: OCT angiography of the left eye of another patient before photodynamic therapy (A), 1 week post-PDT (B) showing occlusion of choroidal vessels, and 5 months post-PDT (C) showing re-perfusion of previously occluded choroidal vessels.

Take Home Points

  • Indocyanine green angiography is the study of choice for imaging choroidal vascular abnormalities in polypoidal choroidal vasculopathy.
  • Ocular coherence tomography angiography (OCTA) allows for direct visualization of anomalous choroidal vasculature, and may be a useful tool in monitoring efficacy of treatments over time.
  • Photodynamic therapy and photodynamic therapy + anti-VEGF has a statistically significantly higher chance of inducing complete regression of choroidal polyps, compared to anti-VEGF alone

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References

  1. Yannuzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina. 1990;10(1):1-8.
  2. Ryan S. Polypoidal choroidal vasculopathy. Retina, 5th ed.  2013:1285-1290.
  3. Honda S, Matsumiya W, Negi A. Polypoidal choroidal vasculopathy: clinical features and genetic predisposition. Ophthalmologica. 2014;231:59-74.
  4. Okubo A, Sameshima M, Uemura A, Kanda S, Ohba N. Clinicopathological correlation of polypoidal choroidal vasculopathy revealed by ultrastructural study. Br J Ophthalmol. 2002;86(10):1093-8.
  5. Imamura Y, Engelbert M, Iida T, Freund KB, Yannuzzi YA. Polypoidal choroidal vasculopathy: a review. Surv Ophthalmol. 2010;55(6):501-515.
  6. Lee WK, Baek J, Dansingani KK, Lee JH, Freund KB. Choroidal morphology in eyes with polypoidal choroidal vasculopathy and normal or subnormal subfoveal choroidal thickness. Retina. 2016;36(Supp 1):S73-S82.
  7. Koh A, Lee WK, Chen L-J, Chen S-J, Hashad Y, Kim H, Lai TY, Pilz S, Ruamviboonsuk P, Tokaji E, Weisberger A, Lim TH. EVEREST STUDY: Efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with ymptomatic macular polypoidal choroidal vasculopathy. Retina. 2012;32:1453-1464.

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