Choroidal coloboma and persistent fetal vasculature (PFV) are independent pediatric ocular disorders, both having serious visual consequences.1,2 Although coloboma develops because of anomalous closure of the fetal cleft, failure of involution of the embryonic vessels results in PFV. Both of these disorders have heterogenous clinical presentations, each with its own set of complications. We present three cases where PFV and choroidal coloboma occurred simultaneously. We discuss the possibility of a cause-effect relationship between these two disorders.
A 1-year-old boy presented at Dr. Rajendra Prasad Centre for Ophthalmic Sciences with a small eye noted by the parents. The child did not follow light in the right eye and resisted occlusion in the left eye. The anterior segments of both eyes were grossly normal on clinical evaluation. On indirect ophthalmoscopy of the right eye, a fibrovascular stalk was noted arising from an anomalous optic disc and attaching to the inferior lens border and adjacent ciliary body (Figure 1A). Additionally, there was an inferior choroidal coloboma involving the optic disc and macula, partially obscured by the large fibrovascular stalk along with surrounding hypopigmented patches. The axial length was 17.5 mm in the right eye and 19.9 mm in the left eye. B-scan ultrasonography revealed a large cyst (8.2 × 5.3 mm) behind the globe (Figure 1B) along with a duct connecting it to the vitreous cavity (Figure 1C). The child was therefore diagnosed as having microphthalmos with orbital cyst and PFV with type 2 choroidal coloboma in the right eye (Ida Mann's classification system).1
(A) Retcam (Clarity Medical Systems, Inc., Pleasanton, CA) fundus photograph of case 1 showing the large fibrovascular stalk arising from the anomalous optic disc in the right eye. Additionally, an inferior choroidal coloboma obscured can also be noted (arrow) along with scattered pigmentary anomalies. There is a large shadow caused by the stalk that obscures the posterior fundus details. (B) Longitudnal ultrasound scan of case 1 depicting a large orbital cyst behind the globe in the right eye (arrow). The choroidal coloboma can also be seen (arrow head). (C) Longitudinal ultrasound scan of case 1 showing the connection between the cyst and the globe in the right eye (arrow) and the vascular stalk (arrowheads).
A 5-year-old boy presented with white reflex in the left eye noticed by the parents at 1 year of age. The child followed light in the left eye but resisted occlusion of the right eye. He had a partially absorbed membranous cataract and esotropia in the left eye, whereas the fellow eye was grossly normal on clinical examination. On ultrasonography of the left eye, a membrane attached to the optic disc and extending to the posterior part of the lens suggestive of PFV was noted. Additionally, there was an excavation of the posterior pole raising suspicion of a coloboma. The axial length was 26.5 mm in the left eye and 22.4 mm in the right eye. The child underwent lens aspiration and posterior capsulorhexis, following which cautery and fracture of the fibrovascular stalk was performed along with anterior vitrectomy. Intraoperatively, the stalk was seen to emanate from the optic disc, which was involved within a type 1 choroidal coloboma (Figure 2A).
(A) Intraoperative fundus photograph of case 2 showing a stalk emanating from the optic disc in the left eye (arrow). (B) Postoperative fundus photograph showing the optic disc with the excised stalk and the choroidal coloboma (arrow).
The details and images of this case have already been published.2 This 8-year-old boy had type 1 iridofundal coloboma with rhegmatogenous retinal detachment in both eyes and PFV in the right eye. Examination additionally revealed an inferior lenticular subluxation in the right eye, with the lens being dragged inferiorly by the pull of the attached PFV (Figure 3). The axial length was 18.8 mm in the right eye and 22.3 mm in the left eye.
Intraoperative photograph of case 3 during vitrectomy depicting a choroidal coloboma, a dysplastic disc, and a fibrovascular stalk with an actively bleeding vessel (white arrow). Reprinted from Journal of American Association for Pediatric Ophthalmology and Strabismus, Volume: 20, Authors: Brijesh Takkar, Parijat Chandra, Vinod Kumar, Renu Agrawal, Title: A case of iridofundal coloboma with persistent fetal vasculature and lens subluxation, Pages: 180–182, Copyright 2016, with permission from Elsevier.
None of these cases had any family history of childhood eye disease and were born of nonconsanguineous marriages. The mothers did not give any history of antenatal or peripartum events, even with specific leading questions for the first trimester. All of these children were evaluated by pediatricians on referral, although only case 2 was found to have a systemic anomaly (ie, gross developmental delay including speech impairment and corpus callosum agenesis as noted on a computed tomography scan). Unfortunately, no genetic tests could be done due to lack of availability. Case 1 was advised to have regular follow-up for complications because laser delimitation was not possible due to the fibrovascular stalk. Case 2 was left aphakic and the condition was stable at 2 months of follow-up with a corrected visual acuity of counting fingers close to the face (Figure 2B). Case 3 underwent vitrectomy with silicone oil for retinal detachment and gained a final visual acuity of 3/60 after 3 months of follow-up.
We have described three cases with association of coloboma and PFV. This occurrence was unilateral, and the coloboma involved both the optic disc and macula in all 3 eyes. These cases had individual combinations with other ocular comorbidities (lens subluxation, cataract, and posterior orbital cyst). Two eyes had microphthalmia. Prior to this report, the combination of PFV and coloboma has been associated with megalolenticonus and morning glory syndrome.2 PFV has also been reported in an eye with optic nerve coloboma and a colobomatous iris defect in a patient with PHACE (posterior fossa malformations–hemangiomas–arterial anomalies– cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe) syndrome.2
Whether this association is causative or coincidental is difficult to prove given the rarity and heterogenous nature of the primary diseases themselves.3,4 It is possible in some cases that PFV may be responsible for development of the coloboma. The mesoblastic theory of coloboma development states that longer persistence of elements of the primary vitreous entering through the fetal cleft into the invaginating optic vesicle from the mesenchyma below the cleft may physically separate the lips of the cleft long enough to allow proliferation of neuroectodermal cells resulting in a coloboma.5,6 Presence of PFV in cases of coloboma has also been suggested by Duke-Elder.5 The above discussed hypothesis explains the findings in all three cases. For case 3, we previously noted that the fetal cleft or the embryonic choroidal fissure started closing in the second month of gestation, which is also the time for development of primary vitreous, followed by its involution in the next month.2,7 Hence a gestational event at or before that stage may be responsible for this anomalous combination, also explaining the lack of family history in these cases. Five cases of uveal coloboma with PFV have been reported previously as part of a large case series of PFV.8 It is best to label this combination of diseases, along with the similar cases discussed previously,2 as a broader posterior segment dysgenesis. This coexistence is much like the one seen in anterior segment dysgenesis syndrome, where multiple morbidities exist together with different severity.
Eyes with PFV are known to be smaller than the fellow eye in unilateral cases. This was found to be consistent in two of our patients (cases 1 and 3). However, in case 2 the eye with dysgenesis had a longer axial length. This is perhaps due to the presence of choroidal coloboma. In a large series of colobomatous eyes where axial length was measured with ultrasound while avoiding the excavated area, the axial length was noted to range from 10 to 31 mm.9 Furthermore, even eyes with PFV can be long and myopia has been shown to be linked to better prognoses.10
Lack of genetic testing is a shortcoming of this report because a genetic or molecular interaction could have explained the simultaneous extraneous (PFV) and missing (coloboma) ocular structures. However, a literature search did not reveal factors common to causation of PFV and coloboma. The commonly implicated factors involved in failure of involution of the PFV include angiopoetin, p53, IE180, and Arf,11 whereas those for coloboma include PAX, SHH, and BMP.12 It is possible that this dysgenesis is a consequence of multiple molecular factors and not a singular one.
Association of PFV and coloboma may lead to profound visual loss despite best efforts. The delicate nature of the structural and molecular interactions involved in the development of the eye allows for coexistence of different ocular morbidities.
- Wadhwa N, Venkatesh P, Sampangi R, Garg S. Rhegmatogenous retinal detachments in children in India: clinical characteristics, risk factors, and surgical outcomes. J AAPOS. 2008;12:551–554. doi:10.1016/j.jaapos.2008.05.002 [CrossRef]
- Takkar B, Chandra P, Kumar V, Agrawal R. A case of iridofundal coloboma with persistent fetal vasculature and lens subluxation. J AAPOS. 2016;20:180–182. doi:10.1016/j.jaapos.2015.12.004 [CrossRef]
- Khokhar S, Gupta S, Gogia V, Nayak B. Salmon pink patch sign: diagnosing persistent fetal vasculature. Oman J Ophthalmol. 2016;9:68–69. doi:10.4103/0974-620X.176128 [CrossRef]
- Khokhar S, Agarwal T, Kumar G, Kushmesh R, Tejwani LK. Lenticular abnormalities in children. J Pediatr Ophthalmol Strabismus. 2012;49:32–37. doi:10.3928/01913913-20110614-01 [CrossRef]
- Duke-Elder S. Congenital and developmental anomalies. In: Duke-Elder S, ed. Textbook of Ophthalmology. London: Henry Kimpton; 1946:1237–1416.
- Bypareddy R, Takkar B, Azad SV, Chawla R. Triple fundal coloboma: irregular closure of the embryonic cleft in the optic cup. BMJ Case Rep. 2016Sep27;2016.
- Bron AJ, Tripathi RC, Tripathi BJ. Development of the human eye. In: Bron AJ, Tripathi RC, Tripathi BJ. Wolff's Anatomy of the Eye and Orbit. London: Chapman and Hall; 1997:620–664.
- 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. doi:10.1016/0039-6257(78)90091-7 [CrossRef]
- Venincasa VD, Modi YS, Aziz HA, et al. Clinical and echographic features of retinochoroidal and optic nerve colobomas. Invest Ophthalmol Vis Sci. 2015;56:3615–3620. doi:10.1167/iovs.15-16596 [CrossRef]
- Cheung JC, Summers CG, Young TL. Myopia predicts better outcome in persistent hyperplastic primary vitreous. J Pediatr Ophthalmol Strabismus. 1997;34:170–176.
- Thornton JD, Swanson DJ, Mary MN, et al. Persistent hyperplastic primary vitreous due to somatic mosaic deletion of the arf tumor suppressor. Invest Ophthalmol Vis Sci. 2007;48:491–499. doi:10.1167/iovs.06-0765 [CrossRef]
- Gregory-Evans C, Williams M, Halford S, Gregory-Evans K. Ocular coloboma: a reassessment in the age of molecular neuroscience. J Med Genet. 2004;41:881–891. doi:10.1136/jmg.2004.025494 [CrossRef]