SUBRETINAL PERIPAPILLARY NEOVASCULARIZATION ASSOCIATED WITH PERSISTENT FETAL VASCULATURE Albert Y. Cheung, MD,* Amir H. Kashani, MD, PhD,† Kimberly A. Drenser, MD, PhD†
Purpose: The purpose of this study was to report a unique case of persistent fetal vasculature presenting as peripapillary choroidal neovascularization. Methods: Ophthalmologic examination, examination under anesthesia, fluorescein angiogram, chart review, review of relevant literature. A 2-year 4-month-old white girl was referred for decreased vision and suspicious retinal findings. Results: Fundus examination of the right eye demonstrated a peripapillary macular scar with old subretinal hemorrhage, subretinal fluid consistent with peripapillary neovascular net, a persistent fetal vascular stalk, and a central posterior lenticular opacity. Fluorescein angiogram of the right eye showed normal arterial filling in the early phase, normal arteriovenous transit, and late staining with mild leakage. Conclusion: This is a unique case of persistent fetal vasculature presenting with the findings of subretinal exudates and choroidal neovascularization that has not been described before. Although the etiology of the choroidal neovascularization is unclear, we postulate it may be a result of the traction from the persistent fetal vasculature stalk in the peripapillary region. These findings may also be secondary to an optic disk anomaly that was not detected on examination. RETINAL CASES & BRIEF REPORTS 8:83–86, 2014
vasculature is usually found in healthy full-term infants.1–3 Familial cases have been reported which suggest that autosomal dominant and recessive inheritance is possible.4 In the developing fetal eye, vascularization begins within 3 weeks of fertilization with the future hyaloid artery entering the eye through the fetal fissure and extending from the posterior to the anterior pole of the eye in an anastomotic network.1,4 In 2 months to 3 months, this vessel network has maximally developed from the hyaloid artery and consists of 1) the vasa hyaloidea propria that branches out to the peripheral vitreous; 2) the posterior tunica vasculosa lentis that covers the posterior pole of the future lens; 3) the iridohyaloid vessels that connect posterior tunica vasculosa lentis with the annular vessel along the equatorial region of the lens; 4) the anterior ciliary vessels that supply the iris and lens; and 5) the anterior tunica vasculosa lentis that grows into the pupillary
From the *Department of Ophthalmology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; and †Department of Vitreoretinal Surgery, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan.
P
ersistent fetal vasculature (PFV) describes an idiopathic syndrome in which the intraocular fetal blood vessels of the primary vitreous remain abnormally after birth instead of regressing.1 It is typically unilateral, sporadic, and not associated with systemic findings; however, bilateral PFV may occur and can be found with systemic syndromes.1–3 Persistent fetal None of the authors have any financial/conflicting interests to disclose. Reprint requests: Kimberly Drenser, MD, PhD, Associated Retinal Consultants, PC, 3535 West, 13 Mile Road, Suite 344, William Beaumont Hospital, Royal Oak, MI 48073; e-mail: [email protected]
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Fig. 1. A. Right eye RetCam (Clarity Medical Systems; Pleasanton, CA) image of the posterior pole demonstrated a hazy view, peripapillary macular scar with subretinal hemorrhage, and possible subretinal fluid consistent with a peripapillary neovascular net inferotemporal to the optic disk. A fibrogliotic stalk is seen emanating from the disk (red arrow). B. Pericentral view through the lens is clear and illustrates the central polar cataract temporally. C. Left eye RetCam image of the posterior pole was unremarkable.
space.1,4 The fetal vasculature begins involuting by the fourth month and has mostly disappeared by birth. Abnormal vessel persistence results in variable manifestations depending on the degree of incomplete regression. This may be associated with relatively normal ocular function or a spectrum of abnormalities that can affect both eye physiology and visual acuity.1,4 Although PFV may present with only anterior or posterior findings, it most commonly presents with a combination of both findings. Anterior segment pathology includes pupillary membranes, centrallydragged ciliary processes, secondary glaucoma, cataract, and retrolenticular opacity. Posterior findings include retinal folds or dysplasia, vitreal membrane or stalk, macular or optic nerve head abnormalities, as well as secondary retinal detachment and intraocular hemorrhages. Management is based on the extent of anterior and posterior segment involvement, with the anterior form having a better visual prognosis than the posterior and combined presentations.4,5 Patients with PFV will often be referred for leukocoria, microphthalmia, decreased vision, and strabismus.3 We describe a case referred for decreased vision with unique findings in the posterior pole associated with peripapillary choroidal neovascularization.
right eye. Examination under anesthesia showed both eyes to have normal pressures and normal size. The anterior segment was grossly normal in both eyes with clear corneas and deep chambers. Dilated fundus examination of the right eye under anesthesia demonstrated a peripapillary macular scar with a persistent fetal vascular stalk, subretinal hemorrhage, and subretinal fluid consistent with a peripapillary neovascular net inferotemporal to the optic disk (Figure 1, A and B). The view of the macula/fovea was slightly obscured when viewed centrally secondary to a central posterior lenticular opacity (Figure 1A compared with Figure 1B). The view through the pericentral aspect of the lens and periphery of the lens was clear (Figure 1B). Close examination revealed a posterior polar opacity that was continuous with a fine stalk emanating from the disk. This was consistent with a partially regressed persistent fetal vascular stalk (Figure 2). Fundus examination of the left eye was normal (Figure 1C). Fluorescein angiogram of the right eye revealed normal arterial filling in the early phase (Figure 3A), showed normal arteriovenous transit (Figure 3B), and revealed late staining and possible mild leakage (Figure 3C). The right eye peripheral examination confirmed avascular loops with a small area of avascular retina in a temporal wedge formation but no signs of other
Case Report A 2-year 4-month-old white girl was referred to our institution for decreased vision and suspicious retinal findings by a local ophthalmologist. The patient was the product of a 37-week pregnancy complicated by hydronephrosis. Delivery was uncomplicated, and she required no neonatal oxygen therapy. She was the first live born child of a nonconsanguineous couple. Family history was significant for a paternal grandfather with keratoconus and muscular dystrophy on the father’s side. The patient’s right eye was noted to have been “lazy” since birth. The rest of the history and review of systems was otherwise unremarkable. On ophthalmologic examination, the patient displayed a right esotropia. The infant objected to covering of the left eye but not the
Fig. 2. Color photograph of the right eye demonstrates the posterior polar opacity (red arrow).
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Fig. 3. A. Fluorescein angiogram of the right eye showed normal arterial filling in the early phase. B. Mid-phase fluorescein angiogram demonstrates increasing staining with otherwise normal arteriovenous transit. C. Late phase fluorescein angiogram demonstrates late staining and possible mild leakage at the lesion site.
neovascularization. Fluorescein angiogram of the left eye was normal in late phase. Although the left eye was grossly normal at the posterior pole, there was an anomalous vascular loop in the temporal periphery. There were no signs of neovascularization in the periphery. A follow-up examination under anesthesia accompanied by fluorescein angiogram at 6 months revealed no additional symptoms and no changes in the anatomy or size of the lesion.
Discussion This is a unique case of PFV presenting with the findings of subretinal exudates and choroidal neovascularization that has not been described before. The clinicopathologic correlations published to date have not demonstrated any signs of choroidal or retinal neovascularization in the natural course of PFV. Choroidal neovascularization has been described postoperatively after a plasmin-assisted vitrectomy in a patient with PFV.6 Previous reports have described retinal dysplasia,3 optic disk coloboma,7 traction retinal detachment,5,8,9 optic nerve hypoplasia or dysplasia,5,8 and exudates associated with PFV and chorioretinitis but not in PFV alone.10 The etiology of choroidal neovascularization in this patient is unclear. We postulate that the choroidal neovascularization demonstrated in this case may be a result of the traction from the PFV stalk in the peripapillary region, although it may also be secondary to an optic disk anomaly that was not evident on examination. Despite careful examination, we could not find any evidence of optic disk anomaly in addition to the neovascularization and associated leakage, exudates, and heme. Treatment options would likely include anti-vascular endothelial growth factor agents, thermal laser, photodynamic therapy, and/or vitrectomy. The aim of treatment would be to prevent progression of vision loss. It is unlikely that any visual recovery would be possible because of the chronicity and location of the lesion. We elected to observe the patient since there was no interval change in symptoms or lesion
characteristics over 6 months. In addition, all treatment options had theoretical risks of worsening an otherwise stable lesion. Intravitreal injection of an anti-vascular endothelial growth factor agent may help decrease any exudative component of the lesion; however, we felt this procedure would also have an unpredictable affect on the persistent fetal vascular stalk. An intravitreal injection may theoretically worsen any tractional component of the lesion, and we believed this was an unwarranted risk. Both thermal laser and photodynamic therapy treatment of a peripapillary lesion pose a serious risk of nerve damage and further vision loss. We believed that a surgical intervention was not warranted for an otherwise stable lesion without a clearly progressive course. Although optical coherence tomography was not obtained, it would potentially be useful to guide management if the lesion was thought to be evolving. Key words: neovascularization, persistent fetal vasculature, persistent hyperplastic primary vitreous, retina, subretinal. References 1. Goldberg MF. Persistent fetal vasculature (PFV): an integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson Memorial Lecture. Am J Ophthalmol 1997;124: 587–626. 2. Reese AB. Persistent hyperplastic primary vitreous. Trans Am Acad Ophthalmol Otolaryngol 1955;59:271–295. 3. Haddad R, Font RL, Reeser F. Persistent hyperplastic primary vitreous. A clinicopathologic study of 62 cases and review of the literature. Surv Ophthalmol 1978;23: 123–134. 4. Silbert M, Gurwood AS. Persistent hyperplastic primary vitreous. Clin Eye Vis Care 2000;12:131–137. 5. Dass AB, Trese MT. Surgical results of persistent hyperplastic primary vitreous. Ophthalmology 1999;106:280–284. 6. Vinekar A, Sund N, Quiram P, Capone A Jr. Choroidal neovascular membrane in persistent fetal vasculature syndrome managed with intravitreal pegaptanib sodium in an infant. Retina 2010;30:S41–S44.
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7. Jensen OA. Persistent hyperplastic primary vitreous. Cases in Denmark 1942-1966. A mainly histopathological study. Acta Ophthalmol (Copenh) 1968;46:418–429. 8. Alexandrakis G, Scott IU, Flynn HW Jr, et al. Visual acuity outcomes with and without surgery in patients with persistent fetal vasculature. Ophthalmology 2000;107:1068–1072.
9. Walsh MK, Drenser KA, Capone A Jr, Trese MT. Early vitrectomy effective for bilateral combined anterior and posterior persistent fetal vasculature syndrome. Retina 2010;30:S2–S8. 10. Corey RP, Flynn JT. Maternal intrauterine herpes simplex virus infection leading to persistent fetal vasculature. Arch Ophthalmol 2000;118:837–840.
Purpose: The purpose of this study was to report a unique case of persistent fetal vasculature presenting as peripapillary choroidal neovascularization. Methods: Ophthalmologic examination, examination under anesthesia, fluorescein angiogram, chart review, review of relevant literature. A 2-year 4-month-old white girl was referred for decreased vision and suspicious retinal findings. Results: Fundus examination of the right eye demonstrated a peripapillary macular scar with old subretinal hemorrhage, subretinal fluid consistent with peripapillary neovascular net, a persistent fetal vascular stalk, and a central posterior lenticular opacity. Fluorescein angiogram of the right eye showed normal arterial filling in the early phase, normal arteriovenous transit, and late staining with mild leakage. Conclusion: This is a unique case of persistent fetal vasculature presenting with the findings of subretinal exudates and choroidal neovascularization that has not been described before. Although the etiology of the choroidal neovascularization is unclear, we postulate it may be a result of the traction from the persistent fetal vasculature stalk in the peripapillary region. These findings may also be secondary to an optic disk anomaly that was not detected on examination. RETINAL CASES & BRIEF REPORTS 8:83–86, 2014
vasculature is usually found in healthy full-term infants.1–3 Familial cases have been reported which suggest that autosomal dominant and recessive inheritance is possible.4 In the developing fetal eye, vascularization begins within 3 weeks of fertilization with the future hyaloid artery entering the eye through the fetal fissure and extending from the posterior to the anterior pole of the eye in an anastomotic network.1,4 In 2 months to 3 months, this vessel network has maximally developed from the hyaloid artery and consists of 1) the vasa hyaloidea propria that branches out to the peripheral vitreous; 2) the posterior tunica vasculosa lentis that covers the posterior pole of the future lens; 3) the iridohyaloid vessels that connect posterior tunica vasculosa lentis with the annular vessel along the equatorial region of the lens; 4) the anterior ciliary vessels that supply the iris and lens; and 5) the anterior tunica vasculosa lentis that grows into the pupillary
From the *Department of Ophthalmology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; and †Department of Vitreoretinal Surgery, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan.
P
ersistent fetal vasculature (PFV) describes an idiopathic syndrome in which the intraocular fetal blood vessels of the primary vitreous remain abnormally after birth instead of regressing.1 It is typically unilateral, sporadic, and not associated with systemic findings; however, bilateral PFV may occur and can be found with systemic syndromes.1–3 Persistent fetal None of the authors have any financial/conflicting interests to disclose. Reprint requests: Kimberly Drenser, MD, PhD, Associated Retinal Consultants, PC, 3535 West, 13 Mile Road, Suite 344, William Beaumont Hospital, Royal Oak, MI 48073; e-mail: [email protected]
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Fig. 1. A. Right eye RetCam (Clarity Medical Systems; Pleasanton, CA) image of the posterior pole demonstrated a hazy view, peripapillary macular scar with subretinal hemorrhage, and possible subretinal fluid consistent with a peripapillary neovascular net inferotemporal to the optic disk. A fibrogliotic stalk is seen emanating from the disk (red arrow). B. Pericentral view through the lens is clear and illustrates the central polar cataract temporally. C. Left eye RetCam image of the posterior pole was unremarkable.
space.1,4 The fetal vasculature begins involuting by the fourth month and has mostly disappeared by birth. Abnormal vessel persistence results in variable manifestations depending on the degree of incomplete regression. This may be associated with relatively normal ocular function or a spectrum of abnormalities that can affect both eye physiology and visual acuity.1,4 Although PFV may present with only anterior or posterior findings, it most commonly presents with a combination of both findings. Anterior segment pathology includes pupillary membranes, centrallydragged ciliary processes, secondary glaucoma, cataract, and retrolenticular opacity. Posterior findings include retinal folds or dysplasia, vitreal membrane or stalk, macular or optic nerve head abnormalities, as well as secondary retinal detachment and intraocular hemorrhages. Management is based on the extent of anterior and posterior segment involvement, with the anterior form having a better visual prognosis than the posterior and combined presentations.4,5 Patients with PFV will often be referred for leukocoria, microphthalmia, decreased vision, and strabismus.3 We describe a case referred for decreased vision with unique findings in the posterior pole associated with peripapillary choroidal neovascularization.
right eye. Examination under anesthesia showed both eyes to have normal pressures and normal size. The anterior segment was grossly normal in both eyes with clear corneas and deep chambers. Dilated fundus examination of the right eye under anesthesia demonstrated a peripapillary macular scar with a persistent fetal vascular stalk, subretinal hemorrhage, and subretinal fluid consistent with a peripapillary neovascular net inferotemporal to the optic disk (Figure 1, A and B). The view of the macula/fovea was slightly obscured when viewed centrally secondary to a central posterior lenticular opacity (Figure 1A compared with Figure 1B). The view through the pericentral aspect of the lens and periphery of the lens was clear (Figure 1B). Close examination revealed a posterior polar opacity that was continuous with a fine stalk emanating from the disk. This was consistent with a partially regressed persistent fetal vascular stalk (Figure 2). Fundus examination of the left eye was normal (Figure 1C). Fluorescein angiogram of the right eye revealed normal arterial filling in the early phase (Figure 3A), showed normal arteriovenous transit (Figure 3B), and revealed late staining and possible mild leakage (Figure 3C). The right eye peripheral examination confirmed avascular loops with a small area of avascular retina in a temporal wedge formation but no signs of other
Case Report A 2-year 4-month-old white girl was referred to our institution for decreased vision and suspicious retinal findings by a local ophthalmologist. The patient was the product of a 37-week pregnancy complicated by hydronephrosis. Delivery was uncomplicated, and she required no neonatal oxygen therapy. She was the first live born child of a nonconsanguineous couple. Family history was significant for a paternal grandfather with keratoconus and muscular dystrophy on the father’s side. The patient’s right eye was noted to have been “lazy” since birth. The rest of the history and review of systems was otherwise unremarkable. On ophthalmologic examination, the patient displayed a right esotropia. The infant objected to covering of the left eye but not the
Fig. 2. Color photograph of the right eye demonstrates the posterior polar opacity (red arrow).
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Fig. 3. A. Fluorescein angiogram of the right eye showed normal arterial filling in the early phase. B. Mid-phase fluorescein angiogram demonstrates increasing staining with otherwise normal arteriovenous transit. C. Late phase fluorescein angiogram demonstrates late staining and possible mild leakage at the lesion site.
neovascularization. Fluorescein angiogram of the left eye was normal in late phase. Although the left eye was grossly normal at the posterior pole, there was an anomalous vascular loop in the temporal periphery. There were no signs of neovascularization in the periphery. A follow-up examination under anesthesia accompanied by fluorescein angiogram at 6 months revealed no additional symptoms and no changes in the anatomy or size of the lesion.
Discussion This is a unique case of PFV presenting with the findings of subretinal exudates and choroidal neovascularization that has not been described before. The clinicopathologic correlations published to date have not demonstrated any signs of choroidal or retinal neovascularization in the natural course of PFV. Choroidal neovascularization has been described postoperatively after a plasmin-assisted vitrectomy in a patient with PFV.6 Previous reports have described retinal dysplasia,3 optic disk coloboma,7 traction retinal detachment,5,8,9 optic nerve hypoplasia or dysplasia,5,8 and exudates associated with PFV and chorioretinitis but not in PFV alone.10 The etiology of choroidal neovascularization in this patient is unclear. We postulate that the choroidal neovascularization demonstrated in this case may be a result of the traction from the PFV stalk in the peripapillary region, although it may also be secondary to an optic disk anomaly that was not evident on examination. Despite careful examination, we could not find any evidence of optic disk anomaly in addition to the neovascularization and associated leakage, exudates, and heme. Treatment options would likely include anti-vascular endothelial growth factor agents, thermal laser, photodynamic therapy, and/or vitrectomy. The aim of treatment would be to prevent progression of vision loss. It is unlikely that any visual recovery would be possible because of the chronicity and location of the lesion. We elected to observe the patient since there was no interval change in symptoms or lesion
characteristics over 6 months. In addition, all treatment options had theoretical risks of worsening an otherwise stable lesion. Intravitreal injection of an anti-vascular endothelial growth factor agent may help decrease any exudative component of the lesion; however, we felt this procedure would also have an unpredictable affect on the persistent fetal vascular stalk. An intravitreal injection may theoretically worsen any tractional component of the lesion, and we believed this was an unwarranted risk. Both thermal laser and photodynamic therapy treatment of a peripapillary lesion pose a serious risk of nerve damage and further vision loss. We believed that a surgical intervention was not warranted for an otherwise stable lesion without a clearly progressive course. Although optical coherence tomography was not obtained, it would potentially be useful to guide management if the lesion was thought to be evolving. Key words: neovascularization, persistent fetal vasculature, persistent hyperplastic primary vitreous, retina, subretinal. References 1. Goldberg MF. Persistent fetal vasculature (PFV): an integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson Memorial Lecture. Am J Ophthalmol 1997;124: 587–626. 2. Reese AB. Persistent hyperplastic primary vitreous. Trans Am Acad Ophthalmol Otolaryngol 1955;59:271–295. 3. Haddad R, Font RL, Reeser F. Persistent hyperplastic primary vitreous. A clinicopathologic study of 62 cases and review of the literature. Surv Ophthalmol 1978;23: 123–134. 4. Silbert M, Gurwood AS. Persistent hyperplastic primary vitreous. Clin Eye Vis Care 2000;12:131–137. 5. Dass AB, Trese MT. Surgical results of persistent hyperplastic primary vitreous. Ophthalmology 1999;106:280–284. 6. Vinekar A, Sund N, Quiram P, Capone A Jr. Choroidal neovascular membrane in persistent fetal vasculature syndrome managed with intravitreal pegaptanib sodium in an infant. Retina 2010;30:S41–S44.
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7. Jensen OA. Persistent hyperplastic primary vitreous. Cases in Denmark 1942-1966. A mainly histopathological study. Acta Ophthalmol (Copenh) 1968;46:418–429. 8. Alexandrakis G, Scott IU, Flynn HW Jr, et al. Visual acuity outcomes with and without surgery in patients with persistent fetal vasculature. Ophthalmology 2000;107:1068–1072.
9. Walsh MK, Drenser KA, Capone A Jr, Trese MT. Early vitrectomy effective for bilateral combined anterior and posterior persistent fetal vasculature syndrome. Retina 2010;30:S2–S8. 10. Corey RP, Flynn JT. Maternal intrauterine herpes simplex virus infection leading to persistent fetal vasculature. Arch Ophthalmol 2000;118:837–840.
