Ciliary body: Ciliary processes are typically elongated and drawn centrally. This can occur in isolation but more commonly occurs when the ciliary processes are incorporated into a RLM. These processes may also drag peripheral retina into the RLM.

Glaucoma: Many eyes with PFV develop secondary angle closure glaucoma. The trabecular meshwork in PFV is of the fetal type in 56% and often incompletely cleaved [4, 18]. Additionally, some eyes with PFV have extension of Descemet’s membrane onto the trabecular meshwork surface [18]. Peripheral anterior synechiae have been reported in 26% of eyes enucleated for PFV [12, 18] and the anterior chamber often shallows as the lens becomes cataractous, occluding the angle. Reese felt that the abnormalities of the angle itself did not play the primary role in the development of glaucoma and that secondary changes were primarily responsible [2, 18]. Intractable glaucoma is a common reason for enucleation in older patients with PFV, often in their teenage years [18].

Uveitis: A phacoanaphylactoid reaction may deve­lop,­ leading to an erroneous diagnosis of uveitis [20]. Of all cases of PFV, 6.5% are initially diagnosed as uveitis [18].

Strabismus: Boniuk and Freedman reported strabismus as the presenting sign in 8% of patients presenting with PFV [18].

Hyphema: 6.5% of patients with PFV present with this finding [18]. The hyphema is likely due to persistence of the fine vessels of the anterior TVL [4].

Vitreous hemorrhage: Patients with PFV can develop vitreous hemorrhages. These hemorrhages can contribute to the glaucoma seen in patients with PFV [21].

including dilated indirect ophthalmoscopy. The patients with RB or in whom the possibility of RB cannot be excluded require prompt referral to a tertiary referral center for further management.

A definitive diagnosis is crucial in determining the appropriate treatment for patients with leukocoria. Most importantly, RB must be excluded with certainty since the treatments for PFV, ROP, or Coats’ disease include intraocular surgery which may have grave consequences in patients with RB. On the other hand, enucleation continues to be a widely employed form of treatment for the eyes with RB but is used sparingly in patients with other forms of leukocoria.

The following diseases are most commonly included in the differential diagnosis of leukocoria:

•Retinoblastoma

•Retinopathy of prematurity (ROP) – stage 5 with total retinal detachment and fibrous membranes

•PFV

•Coats disease

•Toxocariasis

•Vitreous hemorrhage

Other diseases that may present as leukocoria are:

•Posterior cataract

•Choroidal coloboma

•Uveitis

•Retinal detachment

•Congenital retinal folds

•Retinal dysplasia

•Incontenentia pigmenti

•Other tumors (Hemartomas, choroidal hemangioma, and meduloepithelioma)

Table 8.1 presents the major differentiating features of the important disease entities that may be confused with end stage PFV.

8.3.3  Differential Diagnosis

The advanced stage of PFV results in “leukocoria” a word that translates as white pupil from Greek. Among all causes of leukocoria, delayed diagnosis and treatment of retinoblastoma (RB) results in the greatest therapeutic and prognostic consequences. Therefore, all ophthalmologists must act from a very high index of suspicion of RB in all patients with leukocoria. Minimally, all pediatric patients who present with leukocoria of recent onset should undergo a thorough ophthalmologic examination

8.3.3.1  Ancillary Tests

Several ancillary tests can be performed to either confirm the diagnosis of PFV or more importantly to differentiate PFV from other diseases such as RB and ROP. The majority of ancillary tests are particularly useful when media opacity precludes a clear view of posterior segment of the eye. USG, CT scan, and MRI are the major diagnostic modalities used in the investigation of patients with leukocoria.

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.al et Buerk .M.B

ROP retinopathy of prematurity; RB retinoblastoma; NVI neovascularization of iris; TRD tractional retinal detachment; RD retinal detachment; USG ultrasonography; CT scan computed tomography scan; MRI magnetic resonance imaging; EBR external beam radiation; TTT transpupillary thermotherapy

(PHPV) Vitreous Primary Hyperplastic Persistent  8

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•Ultrasonography (USG) – The echographic findings in patients with PFV depend on the location and severity of disease. Usually, USG in PFV shows a small globe although the severity may vary. The lens is often thinner than normal with irregularity of the posterior capsule. The persistent hyaloid artery may be seen as a vitreous band that extends from the posterior surface of the lens to the optic disc and may result in tractional RD in the peripapillary area. Occasionally total RD may be observed in severe cases. USG may identify RB by showing an intraocular mass and calcification. However, the tumor and calcification can be demonstrated accurately by ultrasonographically only in 80% of patients [22]. Tumor extension into the lateral and medial aspect of the orbit and extraocular extension are difficult to diagnose by ultrasonographically [23].

•Computed tomographic scans (CT scan) – Goldberg and associates [24] and Mafee and Goldberg [25]. first described several CT scan features in eyes with PFV that may help to characterize and detect the presence of disease. They recommended the use of intravenous contrast agent and to repeat the scan in lateral decubitus position to derive maximum information. The following CT scan features were described. (1) Microphthalmos which at times may be subtle, is usually observed. (2) Unlike many cases of RB, calcification within and around the globe is absent. (3) Vitreous may show an increased density.

(4) Abnormal intravitreal tissues may enhance following intravenous administration of contrast. (5) The persistence of fetal tissue in the Cloquet’s canal or a congenital nonattachment of the retina may result in tubular, cylindrical, triangular or other forms of discrete intravitreal densities. (6) The serosanguineous fluid in the subhyaloid space or subretinal space may show shifting fluid levels within the vitreous cavity in the decubitus position. (7) The lens may be small and irregular in shape and the anterior chamber may be shallow. (8) Either normal or slightly smaller intraorbital segment of the optic nerve may be observed. These authors also underlined the ease with which the affected eye can be compared with the fellow normal eye by using CT scans in comparison to USG. The CT scan is particularly important in confirming the presence of intraocular calcification which is a hallmark of RB. A possible drawback of CT scan may be its potential for radiation toxicity on the susceptible ocular tissues such as lens.

•Magnetic resonance imaging (MRI) – MRI is more sensitive and specific in differentiating the full range of conditions causing leukocoria. In patients with PFV, T1-weighted MRI images show hyperintensity of the vitreous cavity and/or subretinal space due probably to the presence of proteinaceous fluid or old blood [25]. In contrast, RB is isointense or slightly hyperintense compared with vitreous on T1-weighted and hypointense to vitreous on T2-weighted images [25]. However, the CT scan is superior to MRI for evaluation of patients with RB as the detection of calcification by MRI is not as specific as CT scan.

•Fluorescein angiography – The fluorescein angiography may provide supporting clues for the diagnosis of PFV by revealing the presence of anterior TVL, persistent pupillary membrane vasculature, or a complete or partial brittle star in the retrolental space [26]. Fluorescein angiography is particularly helpful for the diagnosis of Coats’ disease where telengiectatic retinal vessels clearly stand out as hyperfluorescent “light bulb-like” lesions.

8.3.3.2  Prognosis

The visual prognosis for patients with PFV is highly variable. Minimal disease may not have any significant visual consequences and, therefore, may not even require treatment. Mild disease involving either the posterior or anterior segment may require surgery and result in normal vision. Patients with a combination of anterior and posterior PFV with minimal posterior segment involvement may even retain some useful central vision if early surgical intervention is followed by aggressive amblyopia therapy. Advanced anterior PFV may result in severe vision loss.

8.3.3.3  Treatment

A multidisciplinary approach where retinal and pediatric ophthalmologists are involved in the treatment and follow-up of patients with PFV offers the best chance of anatomic or functional success. The location and severity of PFV dictates the treatment strategies. In severe cases surgical intervention may not restore vision, but surgery may help to limit the consequences of angle closure glaucoma by removing the retrolental

tissue and associated cataract. Patients with very severe PFV resulting in end stage glaucoma or severely disorganized globe may require enucleation. Cosmetically acceptable appearance in this group of patients may be achieved by fitting an appropriate prosthesis.

Some historical prognostic indicators for favorable visual results include a young patient, a normal posterior segment, and PFV that has not progressed to flat anterior chamber, extensive synechiae, or intractable glaucoma [3, 27, 28].

Historically, the most frequent surgical indications in eyes with PFV included shallowing of anterior chamber, progressive cataract formation, progressive traction of the ciliary body, intractable glaucoma, and RD. The suggested surgical approaches for the management of PFV include excision of the retrolental tissue and removal of cataract by utilizing a variety of vitrectomy instruments via a limbal or pars plana/pars plicata approach.

Historically, the anatomic and visual success has been linked to the degree of posterior segment involvement and the severity of disease. In the past, a twostage surgical approach was utilized with an intent to preserve the globe and clear the pupillary axis. A vision of 20/400 or better was rarely obtained [29]. In 1986, Karr and Scott [27] reported that 8 of 18 patients with PFV in their series achieved 20/200 or better vision after surgical treatment. They recommended early surgical intervention followed by aggressive amblyopia therapy, but observed the poor outcome in eyes with posteriorsegmentinvolvement.Outcomeshaveimproved with advances in microsurgical techniques, new developments in pediatric aphakic contact lenses, and an early and aggressive amblyopia therapy. Stark et al. [30] reported on the 7 eyes of 7 patients that were operated on by closed-eye vitrectomy techniques through a limbal approach. Six of 7 eyes were treated by amblyopia therapy, out of which, one eye achieved a vision of 20/60 and another one 20/200. The remaining 5 of 7 eyes had count fingers to hand motion vision. However, in 3 of these 5 eyes, reduced vision was attributed to the preexisting macular or optic nerve abnormality. All seven operated eyes were considered surgical/anatomic successes by the authors.

In 1998, Mittra and associates [31], in a retrospective chart review described 14 patients who underwent surgical treatment of combined anterior and posterior PFV via pars plana or limbal approach and were followed for 22 months postoperatively. Twelve out of a

total 14 patients were thought to have visual potential and therefore were treated with aggressive amblyopia therapy. Ten of these 12 patients (83%) achieved a visual acuity of 20/300 or better and 8 (66%) obtained a final vision of 20/100 or better. More importantly, not a single patient had a vision of less than 5/200. By historic comparison, these authors found their results closely approximated those achieved after surgery for unilateral congenital cataract without PFV [32, 33]. They concluded that the presence of PFV alone does not necessarily confer a poor prognosis. The authors recommended that the patients with PFV be evaluated for possible surgical treatment if light perception vision exists. The two patients who did not undergo amblyopia treatment did not progress to phthisis or enucleation within the follow-up period.

In 1999, Dass and Trese [34] described their experience in the management of 35 eyes of 27 patients with PFV. Twenty nine of 35 eyes were managed surgically. Two of these 29 eyes (6.8%) had strictly anterior PFV, and were treated with lensectomy and anterior vitrectomy. Of the remaining 27 eyes, 24 eyes underwent primary lensectomy and vitrectomy via a limbus approach as they had only posterior PFV or a combined anterior and posterior PFV. Two eyes underwent scleral buckling as their primary procedure and one eye underwent enucleation for presumed RB. In this series, 6 of 29 eyes that were managed surgically, achieved 20/60 to 20/800 vision. Two additional patients obtained fix-and-follow vision. All of these 8 eyes had posterior PFV. The authors concluded that surgical treatment of PFV can result in favorable functional and visual outcome despite posterior segment involvement.

In 2002, Anteby et al [35] reported the visual and cosmetic outcomes of 89 eyes of 89 patients with unilateral PFV accompanied by cataract. The mean age on presentation was 0.83 + 1.87 years (range, immediately after birth to 9 years) and the mean follow-up was 6.3 ± 5.7 years. Clinically and ultrasonographically, 29 patients (32.5%) had anterior PFV, 28 patients (31.4%) had posterior PFV, and the remaining 30 patients (33.7%) had combined anterior and posterior disease. Sixty-one of 89 (68.5%) eyes underwent surgery (lensectomy, anterior vitrectomy and removal of persistent hyaloid system) either via a pars plana or limbal approach, while the remaining 28 of 89 eyes (31.4%) were observed without surgery. The decision not to operate was based on the judgment of the investigators due to potential for good visual outcome without