Transparency at Risk

Neovascularization of the Lens

by Olawale Salami

Family history can be an important diagnostic tool.

The human lens and cornea are transparent tissues. In intrauterine life, the lens is nourished by a generous network of fetal capillaries which regress completely by the late fetal period, before birth. The avascular nature of the human lens is an important anatomical feature needed to maintain its optimal transparency.

The invasion of the lens by abnormal or leaky vessels — or neovascularization — may occur in response to several types of insult and is a significant cause of opacity and/or blindness.

Blood vessels that just won’t go away

Persistent hyperplastic primary vitreous (PHPV) is a failure of the regression of a component of fetal blood vessels within the eye. It remains an important cause of amblyopia and visual disabilities in children 1 and should be suspected in any child with leukocoria.

Affected eyes may develop complications including glaucoma, cataracts, intraocular hemorrhages, retinal detachments and/or phthisis, that will further affect the child’s vision. 2 Although the majority of cases are both unilateral and non-hereditary, the occurrence of some familial clinical patterns points to genetic factors and can be inherited as an autosomal dominant or recessive trait. 3

Neovascularization of cornea, iris, optic disc and retina is well-documented. However, the adult human lens and its capsule are avascular and resistant to neovascularization. Latest research findings in the field suggest that the underlying mechanisms that drive neovascularization in the intraocular lens after cataract extraction may be related to diabetes and ischemic central retinal vein occlusion (CRVO), leading to chronic hypoxia and high levels of vascular endothelial growth factors (VEGF) in anterior chamber. 4

Furthermore, anatomical proximity of the intraocular lens (IOL) with pupillary margin and loss of vitreous and its antiangiogenic factors, like opticin have been implicated. 5

A family-centered approach to diagnosis

According to Dr. Manoharan Shunmugam, director of clinical services at the flagship branch of OasisEye Specialists in Kuala Lumpur, during the diagnostic work-up of a patient, it would be helpful to examine parents and siblings, as many genetic conditions — though they may have variable penetrance and expressivity — may have some detectable clinical manifestations.

“For patients with hereditary conditions, it is imperative that the parents receive genetic counseling so that they are aware of the possibilities of these conditions affecting any other children,” Dr. Shunmugam emphasized. “It would also be prudent to ensure that siblings or extended family have a routine eye examination.”

In addition, he advised that “a thorough social and dietary history is necessary, as some modern dietary restrictions have been shown to have an impact on even normal individuals, let alone those with an underlying genetic condition.”

Look out for leukocoria

Early PHPV typically presents with leukocoria in the smaller eye of an infant within one to two weeks of birth.

The classical presentation is that of leukocoria, micro-ophthalmia and a cataract.

However, it’s important to rule out other differential diagnoses of leukocoria, such as retinoblastoma, congenital cataract, Coats’ disease, astrocytic hamartomas (related to tuberous sclerosis), uveitis, toxocariasis, retinopathy of prematurity, Norrie’s disease, Trisomy 13, and WalkerWarburg syndrome.

Spanning from anterior to posterior segment

Anterior PHPV has milder features compared to the posterior phenotype and results in better surgical outcomes and visual results. The anterior subtype has been defined as the presence of a retrolental opacity, elongated ciliary process, or cataract. But it can also include a membranous transformation of the anterior vitreous face causing traction on the peripheral retina, a shallow anterior chamber, poor pupil dilation and microphthalmos.

The posterior subtype has been defined by a stalk of tissue extending from the optic nerve to the retrolental area, causing an elevation of the vitreous membrane from the optic nerve, retinal folds, dysplasia or detachment.

Diagnosing PHPV

By careful clinical examination, PHPV is readily diagnosed by direct visualization of any component of the persistent fetal vasculature. In patients with poor visualization of the fundus, ultrasonography is preferred. In general, ultrasound, computed tomography scanning, magnetic resonance imaging, and fluorescence angiography are all reasonable options for establishing a diagnosis.

Fluorescein angiography, with either a slit-lamp camera or fundus camera, can detect abnormal vasculature in various locations and can be used to visualize the brittle-star configuration. However, peripheral retinal capillary nonperfusion in PHPV should not be confused with those seen patients with retinopathy of prematurity, familial exudative vitreoretinopathy, Norrie disease and incontinentia pigmenti.

Is this a pediatric cataract?

Surgical treatment remains central to the management of PHPV. According to Dr. Shunmugam: “It is essential to double-check that this isn’t a pediatric cataract as there have been reported cases of patients being taken in for cataract surgery then finding a retinal detachment due to the PHPV. There should be a very low threshold for performing B-mode ultrasound in these patients as it is non-invasive, requires no sedation, and reveals much more than can be discerned via ophthalmoscopy in a moving or crying child.”

In cases in which cataract is associated with PHPV, intraoperative bleeding is a potential complication during cataract surgery. 6 The pars plana approach along with endocoagulation has been used successfully by some surgeons, while others have also described an alternative approach using a Fugo plasma blade via an anterior route, which provides better control over the posterior capsulotomy along with minimal traction over the retina and, most important, hemostasis during surgery. 7

In a recent paper 8 , Zhao et al. described a surgical strategy in which anterior PHPV was treated using phacoemulsification with underwater electric coagulation on posterior capsule neovascularization, posterior capsulotomy, anterior vitrectomy, and IOL implantation; while posterior PHPV was treated with lensectomy, posterior vitrectomy, retinal photocoagulation, and IOL implantation or silicone oil tamponade. Postoperatively, visual acuity significantly improved in 25 of 33 eyes (75%) following operations and 3 to 48 months of amblyopia treatment.

These encouraging results demonstrate that early surgical intervention and amblyopia therapy can result in positive treatment outcomes.

Contributing Doctor

Dr. Manoharan Shunmugam is a consultant ophthalmologist, adult and pediatric vitreoretinal surgeon who trained in the United Kingdom. Based in Malaysia since 2013, Dr. Shunmugam has a keen interest in research with publications in a wide range of high-impact journals and has been invited to many international conferences as a speaker. He is also a contributing author of two book chapters in vitreoretinal reference textbooks. He graduated in Scotland and subsequently undertook his ophthalmic specialist training and VR Fellowship in London. En route, he further honed his skills with a pediatric VR fellowship at the prestigious L.V. Prasad Eye Institute, Hyderabad, India – making him one of the few pediatric VR surgeons serving in the Asia-Pacific region. He is currently the director of clinical services at the flagship branch of OasisEye Specialists in Kuala Lumpur, a multi-subspeciality ambulatory eye centre in Malaysia. He continues to serve probono at Hospital Kuala Lumpur and is the honorary secretary of the Malaysian Society of Ophthalmology and is a member of the Asia-Pacific Vitreoretinal Society.

mano.shun@oasiseye.my

REFERENCES:

1 Buerk BM, Sharma MC, Shapiro MJ. Persistent hyperplastic primary vitreous (PHPV). Pediatric Retina. 2011. doi:10.1007/978-3-642-12041-1_8

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8 Pollard ZF. Persistent hyperplastic primary vitreous: Diagnosis, treatment and results. Trans Am Ophthalmol Soc. 1997;95:487-549. Shastry BS. Persistent hyperplastic primary vitreous: Congenital malformation of the eye. Clin Exp Ophthalmol. 2009;37(9):884-990. Kuzmin A, Lipatov D, Chistyakov T, et al. Vascular Endothelial Growth Factor in Anterior Chamber Liquid Patients with Diabetic Retinopathy, Cataract and Neovascular Glaucoma. Ophthalmol Ther. 2013;2(1):41-51. Le Goff MM, Lu H, Ugarte M, et al. The vitreous glycoprotein opticin inhibits preretinal neovascularization. Invest Ophthalmol Vis Sci. 2012;25;53(1):228-34. Dass AB, Trese MT. Surgical results of persistent hyperplastic primary vitreous. Ophthalmology. 1999;106(2):280-284. Khokhar S, Tejwani LK, Kumar G, Kushmesh R. Approach to cataract with persistent hyperplastic primary vitreous. J Cataract Refract Surg. 2011;37(8):1382-1385. Li L, Fan DB, Zhao YT, Li Y, Cai FF, Zheng GY. Surgical treatment and visual outcomes of cataract with persistent hyperplastic primary vitreous. Int J Ophthalmol. 2017;8;10(3):391-399.