Best Description of Retinopathy of Prematurity (ROP)

The NIH website has a wonderful download of an animation showing the stages of Retinopathy of prematurity. This is the Link: http://www.nei.nih.gov/rop/photos.asp.  It is described as Premature infants are at high risk for developing retinopathy of prematurity (ROP).  I have edited with iVideo and used it to explain the disease in recent lectures. At the moment I cannot seem to find the edited version.

Surgery for Retinopathy of Prematurity (ROP)

I have a very nice you tube video that shows creation of the PVD and the removal of the tractional elements.  The PVD was created only partially and then was extended using the shaking and jiggling of the  vitreous with the vitrectomy probe.  As the vitreous separated from the retina surface the tractional elements also separated.  The eye looks great with no cicatrix. This is much better in full size, I advise you goto youtube to view.  Hit the link below.



Link to:  Video of PVD and removal of tractional elements with vitrectomy

Norrie Disease Treatment

This month we reported a case of Norrie Disease that we treated at the first day of birth and was measured to have 20/100 at 2 years.  The retina remains attached.  This is the best visual results reported for Norrie Disease.  While enthusiastic I would like an opportunity to help another child and also learn if this success is repeatable.

For the details please check this months edition of Ophthalmology:  Here is the abstract.

Ophthalmology. 2010 Dec;117(12):2402-6.

Laser photocoagulation at birth prevents blindness in Norrie's disease diagnosed using amniocentesis.

Chow CC, Kiernan DF, Chau FY, Blair MP, Ticho BH, Galasso JM, Shapiro MJ.

Illinois Eye and Ear Infirmary, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.

Abstract

OBJECTIVE: To report the first case of prophylactic laser treatment to prevent blindness in a patient who was diagnosed with Norrie's disease by genetic testing with amniocentesis.

DESIGN: Case report.

PARTICIPANTS: A 2-year-old white boy with Norrie's disease.

METHODS: A 37-week gestational age male with a family history of Norrie's disease was born via Cesarean section after the mother had undergone prenatal amniocentesis fetal-genetic testing at 23 weeks of gestation. A C520T (nonsense) mutation was found in the Norrie's disease gene. After examination under anesthesia confirmed the diagnosis on the first day of life, laser photocoagulation was applied to the avascular retina bilaterally. The patient was followed closely by ophthalmology, pediatrics, and occupational therapy departments.

MAIN OUTCOME MEASURES: Functional outcome, as documented by Teller visual acuity and formal occupational therapy testing, and anatomic outcome, as documented by Retcam photography and fluorescein angiography.

RESULTS: Complete regression of extraretinal fibrovascular proliferation was observed 1 month after laser treatment. No retinal detachment had occurred to date at 24 months. Teller visual acuity at 23 months of life was 20/100 in both eyes. The patient's vision and developmental milestones were age appropriate.

CONCLUSIONS: Pre-term genetic diagnosis with immediate laser treatment after birth may preserve vision in individuals affected with Norrie's disease.

Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

PMID: 20619898 [PubMed - in process]


I am trying to link a pdf. for more details.  The photos may be poor quality, the Ophthalmology website is better.
 Laser for Norrie Disease PDF file

Genetic Testing for Unilateral Persistent Hyperplastic Primary Vitreous (PHPV)

Really, I love your comment.  However, I need to know is the condition mild or severe. How is the retina and macula ?

Now, to answer your question about testing for a unilateral case of Persistent Hyperplastic Primary Vitreous (PHPV) also called Persistent Fetal Vasculature Syndrome (PFVS)

This is a great question for two reasons:
1. I have found that about 20% of cases diagnosed with unilateral PHPV really have asymmetric bilateral disease.  Typically it was Familial Exudative Vitreoretinopathy (FEVR).  Therefore, I like to see a fluorescein angiogram of the periphery in both eyes.  That requires an exam asleep.  Often if the contralateral eye has significant ischemia I will treat it with laser.  this is especially an important exercise if the PHPV (PFVS) is severe and the vision is reduced. This is an example of a unilateral PHPV diagnosis. A lovely photograph that shows truncated vessel growth quire characteristic of FEVR

Figure shows the findings of FEVR in the second eye of a child diagnosed with unilateral PHPV (PFVS)

2. There are cases of FEVR that are unilateral, I would say not really that uncommon (about 10% of FEVR).  However, among FEVR appearance cases only 10% could be confused with PHPV (PFVS).  So the combination is pretty rare.  Unfortunately the genetic testing is helpful only if positive, the confidence in a negative test is not there.  Again, I like a fluorescein angiogram, but here my differentiation between unilateral PFVS (PHPV) and unilateral FEVR is still in the range of a hypothesis.

Of course the parents could get angiograms with good peripheral shots (not an easy task with typical fundus cameras) If there is a positive finding in the parents then the diagnosis is easy.  

Avastin Fever: Part 2

In follow-up, Dr Mintz-Hittner responded to an email I sent yesterday reporting that the report should come out in NEJM in January or February.
I will be checking the journal site daily now.

Avastin Fever

In the last days I had two inquiries from Neonatologists at different level 3 Intensive Care Units enthusiastic about starting to use Avastin instead of laser for primary treatment of ROP.  This is a major topic and I will not adequately treat the controversy tonight, however, I do want to lay out the central question in m mind.  They both attended the Hot Topics in Neonatology conference December 6 - 8 2010 where Dr H. Mintz-Hittner gave a presentation on What's new in ROP.

Background: 1. Laser for ROP is a proven treatment with a 90% success as defined by structural outcome.  It was a prospective randomized trial with 6 years of follow-up and visual outcomes.
2. Avastin is a new molecule created to bind and counteract VEGF (vascular endothelial growth factor).  It is approved by the FDA for colon cancer in order to prevent the growth of blood vessels that nourish the cancer cells, this limits its growth.  In the eye the VEGF is the key player in the development of advanced ROP.

Avastin has a significant effect on ROP and is very promising.  I have used it mainly in cases that were failing standard treatment or had unusual risk factors that made failure likely.  I believe it has helped many of my patients.  However,  I have limited experience with use in primary cases.  I have used it only when laser was impossible.

The BEAT-ROP study was done to compare primary avastin with laser, but the results have not been published and data has not met public scrutiny.  The principle investigator was Dr. Mintz-Hittner and she is pleased with the findings and I gather gave a rather persuasive presentation at the recent meeting.  Still I cannot imagine abandoning a proven effective treatment for Avastin without reading the fine print of the clinical trial.  I must also mention that some Ophthalmologist feel that the anti-VEGF molecule may have a negative effect on development and this remains to be seen.  I suspect mild effects on development since the dose is small and transient, however, it will be difficult to detect this effect among the infants.

October 19 and 20, 2010 I hosted a conference and we discussed the use of Avastin for about 4 hours.  Dr. Mintz-Hittner was a participant and could not present the data because it was embargoed.  I think that the use should start after the report is published.  I hope Dr. Hittner will publish it ASAP.  The amount of effort that she dedicated to this study is an inspiration to me and I feel a little guilty about pushing her to publish.  Nonetheless, I need to see the numbers and fine print and we all need the evidence to replace a scientifically well-established successful treatment.

Consider a Comment or a Question

This Blog has had almost 2000 visits and I want to encourage Comments or Questions.

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.

ETROP

The 6 year follow-up report on the early treatment of ROP came out it is quite interesting. One of the conclusion was that the data supported treatment of type 1 disease and not type 2 disease. This study requires a slow read to appreciate.

link to article: http://archopht.ama-assn.org/cgi/content/full/2010.72v1

Treatment for Norrie Disease

We treated a child with Norrie disease on the first day of life and now 2 years later he has near normal vision. around 20/120. Measurement at this age is not exact. It was accepted for publication by the AAO Journal Ophthalmology. There are a lot of details that I will not put out until after it is published.

We are enthusiastic and hope that it can be duplicated. We would like to duplicate it ourselves because you always wonder if it is just a fluke. Nonetheless it is the most promising report yet by far.