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Bilateral Persistent Fetal Vascular Syndrome (PFVS) aka PHPV

Bilateral Persistent Fetal Vascular Syndrome (PFVS) is very uncommon in my experience.  Moreover, the diagnosis is very suspect because there are other conditions that really look quite similar.

I will make a bit of a fine distinction.   The fetal vessels feed the developing fetal eye but when it matures to near the final form these vessels are no longer needed and the fetal vascular involution or atrophy is part of normal retinal vascular development.  In fact, many conditions that disrupt the vascular development also disrupt the involution of the fetal vascular system.  In distinction PFVS is a non-involution of the fetal vasculature in the face of otherwise normal vascularization.  It is a local disease of the eye and not of the person.

These other disease are often bilateral therefore the bilateral persistent fetal vasculature is mostly a secondary result of another disease of vascular development.  Most common would be Retinopathy of Prematurity (ROP), Familial Exudative Vitreoretinopathy (FEVR) and Norrie Disease.  I have also seen it in bilateral combined optic nerve and retinal coloboma.  These cases are not PFVS but FEVR (for example) with persistent fetal vasculature.

The diagnosis can be differentiated in many cases with the peripheral angiogram or sometimes from genetic testing (however, the diagnosis rate of the blood test is still pretty low and is not much evidence against the presence of the clinical diagnosis)

Stickler Syndrome-Part 3 (Photographic Collection)

Figure 1: A Slit Lamp Photo of a Patient with COL11A mutation and classic Type 2 Vitreous  Anomaly characterized by strands with spheres of condensation. Also described as a "beaded" fibrillar vitreous.

Figure 2:  Large sheets of vitreous floating in the posterior segment of the eye

Figure 3:  Child with stickler disease and the vitreous anomaly includes  prominent vitreous bands as well as anterior scant vitreous.

Figure 4; Perivascular Lattice described in Stickler Syndrome

Figure 5 This is a picture of a giant retinal tear discovered early before development of scarring

Figure 6: A Photograph of a 12 year old boy with total retinal detachment and proliferative vitreoretinopathy.  This eye had  extensive abnormal vitreous adherent to the surface.

Figure 7: a wide angle picture of Figure 6.

Stickler Syndrome-part 2

I think that I would like to explore the indications for referral to the retina specialist or geneticist for a child as a pediatric stickler suspect.  This is a work in progress.  The specialist to whom the patent is sent needs to have a good background in Stickler Disease diagnosis otherwise the consultation will be wasted.  The child in the retinal photograph had seen a Physician with the father asking about Stickler Disease and was told that it was not Stickler disease despite the presence of a number of elements: high myopia, vitreous anomaly, cleft, hearing disorder and double jointedness. (I will check my medical record tomorrow to confirm this memory)

I would recommend that Ophthalmologists refer the following patients for evaluation by a Stickler Involved Physician:

1. Kids with a known Stickler parent 
2. Kids with pedigree showing retinal detachment in a parent especially if there is a second person, sibling or aunt or uncle that also increases the risk.  
3. Kids with the Pierre-Robin Sequence
4. Kids with cleft palate. 
5. Kids with Kneist Syndrome, Marshall Syndrome, and Spondyloepiphyseal Dysplasia Congenita.
6. Children with wedge shaped cataracts. 
7. Finally, the 3-years-old child with more than -3.00 diopter refractive correction.

After the pedigree exploration the clinical diagnosis of Stickler is moved along by recognition of the findings
Major Craniofacial Abnormalities:

• Midfacial Hypoplasia
• Cleft Palate
• Pierre-Robin Series

Hyperflexibilty
Hearing disorder

Eye Findings

• Vitreous Anomaly
• Wedge Shaped Cataract
• Atypical Lattice Degeneration of the Retina
• High Myopia

Finally, the blood tests are quite satisfactory except for the price.

The variability in severity of presentations is quite interesting, even within families one can find different elements.  I hope to gather photos to illustrate the different features above from my collection. 

Stickler Syndrome -Part 1

Left: Gunnar Stickler, MD; Right: Michael Shapiro, MD.

This post is dedicated to Gunnar B. Stickler

Dr Stickler was born June 13, 1925 and died on November 4, 2010. Stickler syndrome remains an important cause of pediatric (and adult) blindness that can be largely prevented. His landmark paper was HEREDITARY PROGRESSIVE ARTHRO-OPHTHALMOPATHY. STICKLER GB, BELAU PG, FARRELL FJ, JONES JD, PUGH DG, STEINBERG AG, WARD LE. Mayo Clin Proc. 1965 Jun;40:433-55.  
I had the pleasure to meet him in 2006. In this photograph I am sitting with Dr Stickler. 
I want to extend a special thank you to Stickler Involved People (SIP) for inviting me to their conference.

A RetCam photograph of a Stickler Disease eye in a young boy at presentation.  It shows a long-standing Giant Retinal Tear with a scrolled edge is seen on the left side and fixed folds around a funnel detachment with a hazy view.  This Giant Retinal Tear is complicated by Proliferative Vireoretinopathy.

Two weeks ago I repaired the retina of a child with clinical stickler disease who had a long standing Giant Retinal Tear and severe PVR. He is pretty typical for about 25% of the cases in children under 12 years of age and probably a larger percentage in even younger kids. They loose their vision but do not really know that it is something to report because it is painless and they can use the other eye. At some point the blind eye will come to the parents attention. In some cases, a minor injury may raise the question about the vision or cause pain that leads to an examination. In other cases, the detached retina cases the eye to degenerate with a cataract, redness and irritation or reduction in size with a drooping lid. Any of these late complications may also bring parental attention to the eye. Late complications usually indicate a poor prognosis for visual recovery.

I did the surgery and the retina has attached, but the vision is very poor because of the long period of detachment. The retina had a retinal cyst which is bad. I hope for improvement, but the general prognosis for this eye is quite guarded.

Fixing a retinal detachment of this sort is challenging and there are some technical issues of interest to retinal surgeons. However, the two major issues regarding Stickler Disease are first, diagnosis and second, prevention.

The biggest worry is the second eye. It has a risk of retinal detachment in the range of 50-70% which is astronomical when compared with the .01% risk in the general population. I prescribed a treatment with laser for prophylaxis.

I perform the prophylactic laser treatment from the ora serrata in a near confluent manner for about 8-12 rows. I will also treat through and around lattice. However, in truth the manner of the prophylaxis remains unresolved. Martin Snead has argued for the superiority of cryotherapy in his important paper on Prophylaxis. Unfortunately, I found his argument unpersuasive. I believe that regardless of the modality that produces the chorioretinal adhesion the key element is treatment to the full circumference from the ora serrata extending posterior and not to areas of lattice alone. Since there is a high rate of giant retinal tears and these are generally not associated with the lattice pathology, it is no surprise that the lattice treatment approach would fail using either cryotherapy or laser. In the past I have also used scleral buckle with good success. Bottom line, A randomized trial would be helpful, but while we would like strong evidence (rather than strong opinion) to determine the best approach, prophylaxis is indicated and Dr Stickler agreed with this in my short conversation with him.

I do not think that treatment is without risk or that it prevents detachment in all cases, rather the risk of 7% bad outcome is better that 70%. Nontheless there remains a large group of ophthalmologists who do not treat preventatively. In adults, they can monitor the eyes for symptoms and perhaps they can get in quickly often before the visual potential is lost. I think regardless of the personal position that the physician must present the opportunity for treatment and ideally a copy of the Snead Paper (Alan Ang, Arabella V. Poulson, Sandy F. Goodburn, Allan J. Richards, John D. Scott, Martin P. Snead, Retinal Detachment and Prophylaxis in Type 1 Stickler Syndrome, Ophthalmology, Volume 115, Issue 1, January 2008, Pages 164-168) After prophylaxis, I still monitor the patient on a 3-4 month basis.

Even more important than the controversy about prophylaxis is the sad situation in which some Ophthalmologist have never heard of this condition and even some Pediatric Ophthalmologists and Retina Specialists remain confused about Stickler Disease. Their patients go undiagnosed and untreated. Pediatric Ophthalmologists and Geneticists need to identify these patients and send them to experienced retinal specialists. My favorite summary about Stickler Disease is in the NIH GeneReviews.  Also another useful resource is Genetics Home Reference.  I will need to write more later about this very important topic, so I will call this part 1.

The Current List of Publications for 2010 (MJ Shapiro)

These are papers that have been published or accepted for publication:
It has been an honor to participate in these papers and a real opportunity to review the literature and think about the topics. I would like to thank all the authors that worked with me.

1. Treating uveitis-associated hypotony with pars plana vitrectomy and silicone oil injection.Kapur R, Birnbaum AD, Goldstein DA, Tessler HH, Shapiro MJ, Ulanski LJ, Blair MP. Retina. 2010 Jan;30(1):140-5.

2. Torpedo maculopathy at the site of the fetal "bulge". Shields CL, Guzman JM, Shapiro MJ, Fogel LE, Shields JA. Arch Ophthalmol. 2010 Apr;128(4):499-501.

3. Progression of type 2 to type 1 retinopathy of prematurity in the Early Treatment for Retinopathy of Prematurity Study. Christiansen SP, Dobson V, Quinn GE, Good WV, Tung B, Hardy RJ, Baker JD, Hoffman RO, Reynolds JD, Rychwalski PJ, Shapiro MJ; Early Treatment for Retinopathy of Prematurity Cooperative Group.
Arch Ophthalmol. 2010 Apr;128(4):461-5.

4 Final Visual Acuity Results in the Early Treatment for Retinopathy of Prematurity Study. The Early Treatment for Retinopathy of Prematurity Cooperative Group*
Arch Ophthalmol. 2010;128(6):(doi:10.1001/archophthalmol.2010.72). Available On-Line

5. Optical Coherence Tomography of Nasal Sliding of the Retina and Temporal Arcades in Retinopathy of Prematurity Hoang, Quan V.; Chau, Felix Y.; Blair, Michael P.; Shapiro, Michael J. Retinal Cases and Brief Reports., doi: 10.1097/ICB.0b013e3181d4271b

6. Anomalous Retinal Vasculature in A Patient With A History of Aortic CoarctationHoang, Quan V.; Blair, Michael P.; Shapiro, Michael J.Retinal Cases and Brief Reports., POST AUTHOR CORRECTIONS, 17 February 2010doi: 10.1097/ICB.0b013e3181cc211e

7. Fluorescein Angiography of Recurrent Retinopathy of Prematurity after Initial Intravitreal Bevacizumab Hoang, QV, Kiernan, DF, Chau, FY, Shapiro, MJ, Blair MP. Archives of Ophthalmology, 2010;128(8):1080-1081. doi:10.1001/archophthalmol.2010.145

8. Laser Photocoagulation at Birth Prevents Blindness in Norrie Disease Diagnosed Using Amniocentesis Chow CC, Kiernan DF, Chau FY, Blair MP, Ticho BH, Galasso JM, Shapiro MJ Ophthalmology. 2010 Jul 8. 

9. Peripheral Retinal Nonperfusion in Septo-Optic Dysplasia (De Morsier Syndrome): Daniel F. Kiernan, MD1,Omar Al-Heeti, BS1Jeremy Keenan, MD, MPH3Steven J. Lichtenstein, MD4Michael P. Blair, MD1,2Ekaterini T. Tsilou, MD5, Michael J. Shapiro, MD1,2Archives of Ophthalmology (Accepted)

10. Effects of Green Diode Laser in the Treatment of Pediatric Coats DiseaseMichael J. Shapiro, M.D.1,2Clement C. Chow, M.D.1Peter A. Karth, M.D.3Daniel F. Kiernan, M.D.1Michael P. BlairAmerican Journal Of Ophthalmology (in press)

11. Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation, Bunin GR, Felice MA, Davidson W, Friedman DL, Shields CL, Maidment A, O’Shea M, Nichols KE, Leahey A, Dunkel IJ, Jubran R, Rodriguez-Galindo C, Schmidt M, Weinstein JL, Goldman S, Abramson DH, Wilson MW, Gallie BL, Chan HSL, Shapiro M, Cnaan A, Ganguly A, Meadows AT. Int J Cancer,

12. Neovascularization after Nonaccidental Trauma. DF Kiernan, MP Blair, MJ Shapiro, Ophthalmology (accepted)

13. In utero diagnosis of Norrie disease and early laser preserves visual acuity. Kiernan DF, Blair MP, Shapiro MJ. Arch Ophthalmol. 2010 Oct;128(10):1382. No abstract available.
PMID: 20938020 [PubMed - indexed for MEDLINE] Letter October 2010

14.Acquired Vasoproliferative Retinal Tumor: A Late Sequela of Retinopathy of Prematurity.  CC Chow, MP Blair, MJ Shapiro.  Archives of Ophthalmology. (Accepted )

15. Multiple Retinal Holes and Peripheral Nonperfusion in Muscle-Eye-Brain Disease. Hoang, Blair, Ramani, Galasso, Shapiro. Accepted to Arch Ophthal. May 2010.

Recent Presentation on APROP

This is perhaps the most difficult form of ROP. This is a movie from my presentation at the EURETINA meeting in Paris over labor day.