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Retinal Physician

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Fluorescein Angiography Pearls for Common Pediatric Retinal Disorders

Five pearls for five diseases.

By: Prashanth G. Iyer, MD, MPH, Anne L. Kunkler, MD, Nimesh A. Patel, MD, Audina M. Berrocal, MD
Retinal Physician March 1, 2021 Vol 18, Issue March 2021 Page(s): 40-42, 44, 46

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Widefield fundus photography with fluorescein angiography (FA) is an essential tool in pediatric retina for diagnosing, guiding treatment, and monitoring retinal vascular conditions. Imaging can either be performed during examination under anesthesia using a contact-based Retcam imaging system (Clarity Medical Systems, Inc.), contact-based Phoenix ICON wide-angle imaging platform (Phoenix Technology Group) or can be performed easily in select cooperative patients in the office setting using noncontact Optos ultrawidefield fundus photography (Optos California; Optos PLC) with or without FA. We highlight 5 pearls using FA for 5 common pediatric retinal conditions.

COATS DISEASE

Coats disease is a unilateral condition predominantly affecting young males due to progressive vascular abnormalities in the retina (Figure 1).1,2 While a genetic component is still being studied, Coats disease can be found in association with a number of syndromes and can have a Coats-like response to many conditions.3 Elevated vascular endothelial growth factor (VEGF) plays an important role in Coats disease.4,5 Presenting signs and symptoms include decreased visual acuity, strabismus, and leukocoria.4

Figure 1. A 21-month-old African American male with Coats disease. Contact fundus photography and fluorescein angiogram of the right eye demonstrating normal retina (A, B). Contact fundus photography of the left eye reveals multiple areas of dense exudation parafoveally (blue arrow), with dilated tortuous vessels (yellow arrow) (C, E). These exudations at times end up concentrated in the fovea. Fluorescein angiogram of the left eye demonstrates tortuous, telangiectatic vessels (yellow arrow) and areas of peripheral nonperfusion and capillary dropout (red arrows) (D). There are aneurysms (green arrow) and peripheral leakage (blue arrow) (F).
Figure 1. A 21-month-old African American male with Coats disease. Contact fundus photography and fluorescein angiogram of the right eye demonstrating normal retina (A, B). Contact fundus photography of the left eye reveals multiple areas of dense exudation parafoveally (blue arrow), with dilated tortuous vessels (yellow arrow) (C, E). These exudations at times end up concentrated in the fovea. Fluorescein angiogram of the left eye demonstrates tortuous, telangiectatic vessels (yellow arrow) and areas of peripheral nonperfusion and capillary dropout (red arrows) (D). There are aneurysms (green arrow) and peripheral leakage (blue arrow) (F).

Fluorescein Angiography Pearls

  1. Peripheral capillary dropout and nonperfusion4
  2. Aneurysms in a “lightbulb” appearance4
  3. Telangiectatic and tortuous vessels especially in the periphery4
  4. Progressive vascular leakage4
  5. Exudation in the macula or in the inferior and temporal quadrants4

RETINOPATHY OF PREMATURITY

Retinopathy of prematurity (ROP) is one of the leading causes of blindness in children secondary to VEGF overexpression (Figure 2). It occurs primary in infants of low birth weight and low gestational age at birth.6 FA has been shown in studies to help improve diagnosis and staging of ROP by identifying vascular anomalies that may not be evident on fundus examination.7 Fluorescein angiography may allow detection and follow-up of these vascular changes and disease progression, allowing for appropriate FA-guided treatment with laser photocoagulation and anti-VEGF therapy.8,9

Figure 2. A 6-month-old African American male born prematurely at 24 weeks with high oxygen demand, diagnosed with retinopathy of prematurity. Contact fundus photography of the right eye reveals vascular tortuosity in the peripheral retina (A, B). Fluorescein angiogram of the right eye demonstrates branching of the terminal vessels (yellow arrow), circumferential vessels (red arrow) and lacey, feathery capillary bed in the periphery (green arrow) (C). Contact fundus photography of the left eye reveals vessels encroaching into the macula (dark blue arrow) and circumferential vessels in the periphery (red arrow) (D, E). Fluorescein angiogram of the right eye demonstrates branching of the terminal vessels (yellow arrow) and a classic homogenous leakage pattern present at the ridge (light blue arrow) (F).
Figure 2. A 6-month-old African American male born prematurely at 24 weeks with high oxygen demand, diagnosed with retinopathy of prematurity. Contact fundus photography of the right eye reveals vascular tortuosity in the peripheral retina (A, B). Fluorescein angiogram of the right eye demonstrates branching of the terminal vessels (yellow arrow), circumferential vessels (red arrow) and lacey, feathery capillary bed in the periphery (green arrow) (C). Contact fundus photography of the left eye reveals vessels encroaching into the macula (dark blue arrow) and circumferential vessels in the periphery (red arrow) (D, E). Fluorescein angiogram of the right eye demonstrates branching of the terminal vessels (yellow arrow) and a classic homogenous leakage pattern present at the ridge (light blue arrow) (F).

Fluorescein Angiography Pearls

  1. Shunt vessels along the vascular-avascular junction10
  2. Vessels encroaching onto the fovea11
  3. Branching patterns such as tangles or circumferential vessels10
  4. Lacy, feathery capillary bed11
  5. Neovascularization lesions with “popcorn” tufts, and leakage at the ridge10

PERSISTENT FETAL VASCULATURE

Persistent fetal vasculature arises from failure of the hyaloid vasculature to undergo normal involution (Figure 3). It is believed this is a sporadic, nonheritable congenital disorder with a variety of clinical presentations.12,13 Persistent fetal vasculature can be differentiated from other similar, inherited conditions by its unilateral presentation.14 Recent work shows that there are peripheral retinal changes in the fellow eye of these patients.15

Figure 3. An 8-month-old male with persistent fetal vasculature. Contact fundus photography of the right eye reveals elevation of the optic disc with a fibrovascular stalk extending to the lens (red arrow) (A). Focus on the anterior portion of the stalk shows its vascular nature (B). Elongated ciliary processes are seen (C). Fluorescein angiogram of the right eye demonstrates increased leakage of the fibrovascular stalk (red arrow), staining of the juxtapapillary tissue (blue arrow), and disorganized retinal vessels (orange arrow) (D, G). Fluorescein angiogram reveals the fine vessels in the fibrovascular stalk (red arrow) (E). Elongated ciliary processes with vascular connections to the lens can be visualized with fluorescein (green arrow) (F).
Figure 3. An 8-month-old male with persistent fetal vasculature. Contact fundus photography of the right eye reveals elevation of the optic disc with a fibrovascular stalk extending to the lens (red arrow) (A). Focus on the anterior portion of the stalk shows its vascular nature (B). Elongated ciliary processes are seen (C). Fluorescein angiogram of the right eye demonstrates increased leakage of the fibrovascular stalk (red arrow), staining of the juxtapapillary tissue (blue arrow), and disorganized retinal vessels (orange arrow) (D, G). Fluorescein angiogram reveals the fine vessels in the fibrovascular stalk (red arrow) (E). Elongated ciliary processes with vascular connections to the lens can be visualized with fluorescein (green arrow) (F).

Fluorescein Angiography Pearls

  1. Brittle star configuration and leakage from the fibrovascular stalk16
  2. Leakage extending to the iris margin — “hairpin loop”17
  3. Retinal disorganization18
  4. Peripheral capillary nonperfusion in the involved eye and in the fellow eye15,18
  5. Staining of the juxtapapillary tissue18

FAMILIAL EXUDATIVE VITREORETINOPATHY

Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disease characterized by incomplete vascularization of the peripheral retina and retinal ischemia, leading to abnormal angiogenesis (Figure 4).19 It is associated with multiple gene mutations about 50% of the time.20 It is seen in infants with full-term birth and normal birth weight, and it is progressive over many years.20 In babies born prematurely, FA helps us to differentiate it from ROP. We described these cases as ROPER (ROP vs FEVR).10

Figure 4. An 8-month-old female with familial exudative vitreoretinopathy. Contact fundus photography of the right eye shows an unremarkable fundus (A). Fluorescein angiogram of the right eye reveals subtle peripheral nonperfusion (red arrow) (B). Fluorescein angiogram at the periphery demonstrates pruning of the vessels (yellow) and straightening of the arcade (green arrow) (C). Fundus photography of the left eye demonstrates retinal fold (orange arrow) (D). Fluorescein angiogram of the left eye demonstrates retinal fold (orange arrow), changes and dragging of the retinal vasculature (green arrow), peripheral nonperfusion (red arrow) and peripheral leakage (blue arrow) (E). Fluorescein angiogram at the periphery demonstrates pruning and subtle sprouting of the vessels (yellow arrow) and the retinal fold (orange arrow) (F).
Figure 4. An 8-month-old female with familial exudative vitreoretinopathy. Contact fundus photography of the right eye shows an unremarkable fundus (A). Fluorescein angiogram of the right eye reveals subtle peripheral nonperfusion (red arrow) (B). Fluorescein angiogram at the periphery demonstrates pruning of the vessels (yellow) and straightening of the arcade (green arrow) (C). Fundus photography of the left eye demonstrates retinal fold (orange arrow) (D). Fluorescein angiogram of the left eye demonstrates retinal fold (orange arrow), changes and dragging of the retinal vasculature (green arrow), peripheral nonperfusion (red arrow) and peripheral leakage (blue arrow) (E). Fluorescein angiogram at the periphery demonstrates pruning and subtle sprouting of the vessels (yellow arrow) and the retinal fold (orange arrow) (F).

Fluorescein Angiography Pearls

  1. Venous–venous shunting10
  2. Irregular sprouting vascularization10
  3. Retinal folds20
  4. Straightening of the arcades/vessels20
  5. Pruning of peripheral vessels10

INCONTINENTIA PIGMENTI

Incontinentia pigmenti (IP) is a rare X-linked dominant syndrome characterized by progressive vascular occlusive events leading to skin lesions, dental abnormalities, neurological findings, and retinal disease (Figure 5). It is thought to be caused by mutations in the IKBKG gene on the X-chromosome, thus primarily affecting females.21 Other ocular abnormalities can be seen in IP, including cataracts, strabismus, corneal opacities, uveitis, optic atrophy, and pthisis.22,23 Fluorescein angiography is essential in the staging of this disease as soon as the diagnosis is suspected or confirmed to avoid retinal detachments and blindness.24

Figure 5. A 16-month-old female with incontinentia pigmenti. Contact fundus photography of the right eye shows nonspecific vascular changes and a blunted foveal reflex (A). Fluorescein angiogram of the right eye reveals vessel bending (yellow arrow), peripheral leakage (blue arrow), enlarged foveal avascular zone (green arrow), and peripheral nonperfusion (red arrow) (B, C). Fundus photography and FA of the left eye are unremarkable (D, E). External photography of the chest in this child reveals hyperpigmented, brown linear skin lesions (blue arrow) (F).
Figure 5. A 16-month-old female with incontinentia pigmenti. Contact fundus photography of the right eye shows nonspecific vascular changes and a blunted foveal reflex (A). Fluorescein angiogram of the right eye reveals vessel bending (yellow arrow), peripheral leakage (blue arrow), enlarged foveal avascular zone (green arrow), and peripheral nonperfusion (red arrow) (B, C). Fundus photography and FA of the left eye are unremarkable (D, E). External photography of the chest in this child reveals hyperpigmented, brown linear skin lesions (blue arrow) (F).

Fluorescein Angiography Pearls

  1. Abnormal vascular loops and bending of vessels25
  2. Foveal blunting and enlarged foveal avascular zone26
  3. Arteriovenous shunting25
  4. Peripheral avascularity and leakage25
  5. Retinal arterial occlusions27 RP

Prashanth G. Iyer, MD, MPH, is a vitreoretinal fellow in the department of ophthalmology at the Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine in Miami, Florida. Nimesh A. Patel, MD, is a vitreoretinal surgeon in the department of ophthalmology at Massachusetts Eye and Ear Infirmary of Harvard Medical School in Boston, Massachusetts. Anne L. Kunkler, MD, is a second-year resident with the department of ophthalmology at the Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida. Audina M. Berrocal, MD, is a professor of clinical ophthalmology, medical director of pediatric retina and retinopathy of prematurity, and vitreoretinal fellowship director at the Bascom Palmer Eye Institute in Miami, Florida. The authors report no related disclosures. The authors would like to acknowledge Alexander Rodriguez and the Bascom Palmer Eye Institute department of photography for their assistance with the images in this article. Reach Dr. Berrocal at aberrocal@med.miami.edu.

REFERENCES

  1. Ghorbanian S, Jaulim A, Chatziralli IP. Diagnosis and treatment of Coats’ disease: a review of the literature. Ophthalmologica. 2012;227(4):175-182. doi:10.1159/000336906
  2. Villegas VM, Gold AS, Berrocal AM, Murray TG. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation. Clin Ophthalmol. 2014;8:973-976. Published 2014 May 16. doi:10.2147/OPTH.S62816
  3. Black GC, Perveen R, Bonshek R, et al. Coats’ disease of the retina (unilateral retinal telangiectasis) caused by somatic mutation in the NDP gene: a role for norrin in retinal angiogenesis. Hum Mol Genet. 1999;8(11):2031-2035. doi:10.1093/hmg/8.11.2031
  4. Shields JA, Shields CL, Honavar SG, Demirci H. Clinical variations and complications of Coats disease in 150 cases: the 2000 Sanford Gifford Memorial Lecture. Am J Ophthalmol. 2001;131(5):561-571. doi:10.1016/s0002-9394(00)00883-7
  5. Sigler EJ, Randolph JC, Calzada JI, Wilson MW, Haik BG. Current management of Coats disease. Surv Ophthalmol. 2014;59(1):30-46. doi:10.1016/j.survophthal.2013.03.007
  6. Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med. 2012;367(26):2515-2526. doi:10.1056/NEJMra1208129
  7. Ng EY, Lanigan B, O’Keefe M. Fundus fluorescein angiography in the screening for and management of retinopathy of prematurity. J Pediatr Ophthalmol Strabismus. 2006;43(2):85-90.
  8. Temkar S, Azad SV, Chawla R, et al. Ultra-widefield fundus fluorescein angiography in pediatric retinal vascular diseases. Indian J Ophthalmol. 2019;67(6):788-794. doi:10.4103/ijo.IJO_1688_18
  9. Early Treatment For Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol. 2003;121(12):1684-1694. doi:10.1001/archopht.121.12.1684
  10. John VJ, McClintic JI, Hess DJ, Berrocal AM. Retinopathy of prematurity versus familial exudative vitreoretinopathy: report on clinical and angiographic findings. Ophthalmic Surg Lasers Imaging Retina. 2016;47(1):14-19. doi:10.3928/23258160-20151214-02
  11. Mansukhani SA, Hutchinson AK, Neustein R, Schertzer J, Allen JC, Hubbard GB. Fluorescein angiography in retinopathy of prematurity: comparison of infants treated with bevacizumab to those with spontaneous regression. Ophthalmol Retina. 2019;3(5):436-443. doi:10.1016/j.oret.2019.01.016
  12. Hunt A, Rowe N, Lam A, Martin F. Outcomes in persistent hyperplastic primary vitreous. Br J Ophthalmol. 2005;89(7):859-863. doi:10.1136/bjo.2004.053595
  13. Yusuf IH, Patel CK, Salmon JF. Unilateral persistent hyperplastic primary vitreous: intensive management approach with excellent outcome beyond visual maturation. BMJ Case Rep. Published January 6, 2015. doi:10.1136/bcr-2014-206525
  14. Shaikh S, Trese MT. Lens-sparing vitrectomy in predominantly posterior persistent fetal vasculature syndrome in eyes with nonaxial lens opacification. Retina. 2003;23(3):330-334. doi:10.1097/00006982-200306000-00007
  15. Laura DM, Staropoli PC, Patel NA, et al. Widefield fluorescein angiography in the fellow eyes of patients with presumed unilateral persistent fetal vasculature. Ophthalmol Retina. Published online ahead of print July 25, 2020. doi:10.1016/j.oret.2020.07.020
  16. Pellegrini M, Shields CL, Arepalli S, Shields JA. Posterior tunica vasculosa lentis and “brittle star” of persistent fetal vasculature. J Pediatr Ophthalmol Strabismus. 2014;51 Online:e69-e71. Published 2014 Nov 19. doi:10.3928/01913913-20141111-01
  17. Pollard ZF. Persistent hyperplastic primary vitreous: diagnosis, treatment and results. Trans Am Ophthalmol Soc. 1997;95:487-549.
  18. Gulati N, Eagle RC Jr, Tasman W. Unoperated eyes with persistent fetal vasculature. Trans Am Ophthalmol Soc. 2003;101:59-65.
  19. Miyakubo H, Hashimoto K, Miyakubo S. Retinal vascular pattern in familial exudative vitreoretinopathy. Ophthalmology. 1984;91(12):1524-1530. doi:10.1016/s0161-6420(84)34119-7
  20. Ranchod TM, Ho LY, Drenser KA, Capone A Jr, Trese MT. Clinical presentation of familial exudative vitreoretinopathy. Ophthalmology. 2011;118(10):2070-2075. doi:10.1016/j.ophtha.2011.06.020
  21. Swinney CC, Han DP, Karth PA. Incontinentia pigmenti: a comprehensive review and update. Ophthalmic Surg Lasers Imaging Retina. 2015;46(6):650-657. doi:10.3928/23258160-20150610-09
  22. Minic S, Obradovic M, Kovacevic I, Trpinac D. Ocular anomalies in incontinentia pigmenti: literature review and meta-analysis. Srp Arh Celok Lek. 2010;138(7-8):408-413. doi:10.2298/sarh1008408m
  23. Goldberg MF. The blinding mechanisms of incontinentia pigmenti. Trans Am Ophthalmol Soc. 1994;92:167-179.
  24. Huang NT, Summers CG, McCafferty BK, Areaux RG, Koozekanani DD, Montezuma SR. Management of retinopathy in incontinentia pigmenti: a systematic review and update. J Vitreoret Dis. 2018;2:39-47.
  25. Liu TYA, Han IC, Goldberg MF, Linz MO, Chen CJ, Scott AW. Multimodal retinal imaging in incontinentia pigmenti including optical coherence tomography angiography: findings from an older cohort with mild phenotype. JAMA Ophthalmol. 2018;136(5):467-472. doi:10.1001/jamaophthalmol.2018.0475
  26. Goldberg MF. Macular vasculopathy and its evolution in incontinentia pigmenti. Trans Am Ophthalmol Soc. 1998;96:55-72.
  27. Cernichiaro-Espinosa LA, Patel NA, Bauer MS, et al. Revascularization after intravitreal bevacizumab and laser therapy of bilateral retinal vascular occlusions in incontinentia pigmenti (Bloch-Sulzberger syndrome). Ophthalmic Surg Lasers Imaging Retina. 2019;50(2):e33-e37. doi:10.3928/23258160-20190129-16

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