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Volume 10, Number 3 |
December
2014 |
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Inside
This Issue
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This e-newsletter is provided free to doctors through industry support from |
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FROM
THE DESK OF THE EDITOR
I recently came back from the American Academy of Optometry
meeting in Denver. Great meeting, but it was COLD! Real COLD! Not sure why people would choose to subject
themselves to that by choice! Nice city, but COLD! Anyway, while there, I participated in the first ever Retina
Special Interest Group (SIG) Symposium on Saturday. I had a panel of 4 experts speaking about their area of
interest: a PhD on dark adaptometry and its role in early AMD detection; an MD/PhD on the Genetics of AMD; a PhD
from Tufts discussing lutein and its role in both eye and brain health; and a retinal specialist discussing some
new drugs and delivery systems for AMD in the pipeline.
LIVE
POLL |
There is growing evidence that blue light may be damaging to the retina, as well as other ocular tissues. With that in mind, do you find it important to recommend blue blockers:
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It was very well received by most people I talked to.
But what I liked was how such a diverse group happily participated in this discussion at an Optometry meeting.
In fact, the retinal specialist was so impressed with the meeting, he has asked me if he can come to
another meeting, and how he can become a fellow in the Academy! Later I had dinner with three of the panelists,
and had lively conversation on a variety of topics, some eye related and some not. My point is that once we
get together with other specialists, either ophthalmologists, retinal specialists or research PhDs, with
common interests, I think we find we have much more in common than we think, and less different than we expect.
I also want to acknowledge the new ORS board coming in: Brad Sutton as President; yours truly (Steve Ferrucci, in case
you are not paying attention) as Vice President; Jeff Austin as Secretary; and Chris Suhr as Treasurer. I look forward
to working with you all to make the ORS even better. I also want to thank the outgoing board: Joe Pizzimenti
(President); Mark Dunbar (Vice President); Brad Sutton (Secretary); and Sherrol Reynolds (Treasurer). You all did
a fantastic job, and just hope we can fill your shoes admirably!
Lastly, we are starting to plan for an ORS meeting for 2015, so look out for more information in the near future!
Steven Ferrucci, O.D., F.A.A.O.
Editor in Chief
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PRESIDENT'S MESSAGE
Joseph J. Pizzimenti, O.D., F.A.A.O.
'Tis the Season to Nourish Your Retina
Now begins the annual whirlwind of Holiday parties, large family meals, and celebration. With so many opportunities to over-indulge, I am trying a new strategy this year. The retina strategy. That is, steering my consumption toward those foods that benefit the most important of ocular tissues.
AUGUST 2014
POLL RESULTS
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Certain nuts and seeds supply the retina with Vitamin E, the body's most powerful lipid soluble antioxidant,
shown to provide significant protection against AMD. So, at the start of a cocktail party, enjoy a healthy mix
of unsalted (or lightly salted) peanuts, almonds, walnuts, cashews, sunflower seeds, and hazelnuts/filberts.
We all know that spinach, kale, and collards are rich in protective xanthophylls (zeaxanthin and lutein). These leafy
greens may accompany any lean protein or serve as a featured dish for those on plant-based diets. My protein of choice
is fish, which is consistent with the Italian tradition known as the "Feast of the Fishes". On la vigilia (Christmas
Eve) Italians serve as many as 7, 10, or even 13 fish dishes. Wild salmon oreganata—baked with garlic and bread
crumbs—can be served over a bed of spinach, providing macular pigments as well as omega-3 long chain fatty
acids. Omega-3 FA is plentiful in ocular tissues, may reduce risk of AMD, and is also important in general health owing
to its inflammatory modulation.
These festive times call for a glass of wine to accompany our meal. A glass or two of red wine will supply ocular
tissues with resveratrol, the polyphenols found in high concentrations in the grape skins. Polyphenols are powerhouses
that may help kill cancer cells, reduce blood pressure, and lower cholesterol. Cannonau grapes from Sardinia, Malbec
from Argentina, and Nebbiolo grapes from northern Italy are wonderful options.
The bright orange color of pumpkin is a dead giveaway that this food is loaded with an important antioxidant,
beta-carotene. Beta-carotene is converted to vitamin A in the body to perform many important functions in overall health.
A diet rich in foods containing beta-carotene may reduce the risk of developing certain types of cancer and offers
protect against heart disease and AMD. A reasonable size slice of pumpkin bread or crustless pumpkin pie (my favorite) is
a staple in our home.
Top off the meal with some fresh fruit (berries and cherries are powerful antioxidants and cancer fighters) and
dark chocolate (at least 70% cacao). Packed with healthy chemicals like antioxidant flavonoids, a square of two
of chocolate goes nicely with the last few sips of red wine.
Happy holidays to you and yours, and best of success to the incoming ORS President, Brad Sutton, and new officers.
See you in 2015!
Joe
ORS President
YOU
MAKE THE DIAGNOSIS
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Figure 1: Fundus Photos OS |
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Figure 2: Left eye reveals foveal hypoplasia, shallow foveal contour,
and displaced foveal position towards the optic nerve. |
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Figure 3: SD-OCT of the temporal retina where regressed neovascularization
is present. A retinoschisis and neurosensory retinal detachment can be seen in the top two images.
The bottom image reveals a blood vessel intruding into the vitreal space and blocking the transmittance
to the retinal layers beneath. |
Answer appears later in newsletter.
CLINICAL
PEARLS
Tilted Discs
By Andrew Gurwood, O.D., F.A.A.O., Diplomate
ORS Founding Fellow
Ophthalmoscopically, tilted optic discs often appear to be longer horizontally than vertically.
They are usually accompanied by an inferonasal crescent. The tilted disc may be associated with
an outpouching of the globe (staphyloma) in the quadrant where the crescent is located (referred to
as nasal fundus ectasia). Fuchs' coloboma is another name that has been applied to the entity.
Visual acuity in eyes with tilted discs often may be mildly decreased or normal. In those with
fundus ectasia, a relative temporal field defect may be uncovered. In bilateral cases,
these abnormalities have the potential to produce bitemporal hemianopia. The treatment is
patient education and full time polycarbonate protection.
References
1. Alexander, L.T. Congenital and acquired anomalies of the optic nerve head. In: Alexander, L.S. Primary Care
of The Posterior Segment. Appleton & Lange, Norwalk, CN 1994: 89–170.
Blue Light and AMD
By Diana Shechtman, O.D., F.A.A.O.
ORS Fellow
High energy visible light may be both beneficial and dangerous. Blue
light is an essential component of vision: it is required for color
perception, it is linked to pupil size and it affects sleep/wake cycles,
as well as mood and memory. Yet, cumulative effects may induce
accelerated retinal cell apoptosis, linked to degenerative changes, such as AMD.
Cumulative exposure to blue light may be associated with retinal damage.
Given the increase use of LED (digital devices)/CFL (energy efficient
bulbs) and knowing that most blue light is not filtered out by the
anterior segment ocular tissue, many companies are starting to incorporate these lenses into their lines.
Perhaps it is time to start utilizing theses lenses for patients with AMD, at risk for AMD, or those
exposed to above average levels of blue light.
Documenting Retinal Lesions
By William J. Denton, O.D., F.A.A.O., F.S.L.S.
ORS Fellow
When you come across a retinal lesion that is atypical and you are unaware of what it is, it is important
to describe as best as possible (or take a picture) in the chart. Dimensions in disc diameters (DD),
color, texture description, landmarks nearby, elevation and retinal layer should be included. Furthermore,
if there are any exudates, pigment, lipofuscin, drusen, atrophy or sclera, they should also be mentioned.
After a detailed description, a list of differential diagnoses should be included. There are many books that
you can purchase to assist with differentials. Ocular Differential Diagnoses by F.H.Roy is one example and
is available online. Once you make your list, your top choice should be your working diagnosis. If you
cannot narrow down your list, you always have the option to provide a broad diagnosis code like
chorioretinal scar (313.30), unspecified retinal disorder (362.9) or other retinal disorder (362.89). If you
are too broad the patient's insurance company may not recognize or reimburse for it. The goal is to have
a diagnosis that is as specific as possible, but only if you have confidence in it.
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JOURNAL
ABSTRACTS
The Risk of Toxic Retinopathy in Patients on Long-term Hydroxychloroquine Therapy.
The purpose of this study was to reassess the prevalence and risk factors for hydroxychloroquine toxicity and
to determine optimal safe dosage levels that will minimize toxicity. It is believed the risk of retinal toxicity
is higher then originally believed because many cases are often advanced when finally detected and with
advanced imaging technologies retinopathy can be detected earlier.
The study was a retrospective case-control study in an integrated health organization of approximately 3.4 million
members among 2361 patients who had used hydroxychloroquine continuously for at least 5 years and who were evaluated
with visual field testing or SDOCT.
The authors determined that real body weight predicted risk better than ideal body weight and was used for
all calculations. The overall prevalence of hydroxychloroquine retinopathy was 7.5% but varied with daily
consumption and with duration of use. For daily consumption of 4.0 to 5.0 mg/kg, the prevalence of retinal
toxicity remained less than 2% within the first 10 years of use but rose to almost 20% after 20 years of use.
Other major risk factors include kidney disease and concurrent tamoxifen citrate therapy.
These data suggest that hydroxychloroquine retinopathy is more common than previously recogniretzed, especially at
high dosages and long duration of use. While no completely safe dosage is identified from this study, daily consumption
of 5.0 mg/kg of real body weight or less is associated with a low risk for up to 10 years.
Melles RB, Marmor, M. JAMA Ophthalmology. Published online October 2, 2014.
Effects of Disease Stage on Progression of Hydroxychloroquine (Plaquenil) Retinopathy.
The study showed that the effects of Plaquenil retinopathy progressed even after the drug stopped. The study
also evaluated clinical findings in patients with Plaquenil retinopathy. They were monitored with repeated
anatomical and functional examination for 13 to 40 months after the drug was stopped in a referral practice at
a university medical center. Eleven patients participated with the severity of toxic effects categorized as
early (patchy parafoveal damage shown on field or objective testing), moderate (a 50%-100% parafoveal ring
of OCT thinning but intact RPE), and severe (visible bulls'-eye damage). The results of the study were that the
visual acuity and visual fields showed no consistent change. The fundus autofluorescence showed little to no
change except in severe cases, which the bull's-eye damage expanded progressively. OCT cross sections showed
little visible change in early and moderate stage cases but progressive foveal thinning (7 µms/year) and loss
of ellipsoid zone (100 µms/year) in severe cases. The measurements also showed some foveal thinning
(4 µms/year) and deepening of parafoveal loss in moderate cases. The outcome of the study showed that
patients with Plaquenil retinopathy involving the RPE demonstrated progressive damage on OCT for at least three
years after the drug was discontinued, which included loss of foveal thickness and cone structure. Thus, the
early recognition of Plaquenil toxicity before fundus changes are visible will significantly minimize late
progression and the risk of visual loss.
Marmor M, Hu J. JAMA Ophthalmology 2014 June; 132(9): 1105-1112.
Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results
of the Phase 3 GALILEO Study.
This randomized, double-masked, phase 3 study evaluates intravitreal aflibercept for treatment of macular edema secondary
to central retinal vein occlusion (CRVO).
A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept
(n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks;
the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to
76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The proportion
of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week
24 and 57.3% vs 29.4% at week 76. Mean µm change from baseline central retinal thickness was –448.6
vs –169.3 at week 24 and –389.4 vs –306.4 at week 76.
The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when
treatment intervals were extended. Therefore, patients with macular edema following CRVO benefited from early
treatment with intravitreal aflibercept.
Ogura Y, Roider J, Korobelnik J, et al. American Journal of Ophthalmology Volume 158, Issue 5, Pages
1032–1038.e2, November 2014.
Supplementation with Three Different Macular Carotenoid Formulations in Patients with Early Age-Related
Macular Degeneration.
The purpose of this study was to investigate the impact of three different macular carotenoid formulations on
macular pigment optical density and visual performance in subjects with early age-related macular degeneration.
Fifty-two subjects were supplemented and followed for 12 months, 17 of them were in intervention Group 1 (20 mg/day lutein
and 2 mg/day zeaxanthin); 21 in Group 2 (10 mg/day meso-zeaxanthin, 10 mg/day lutein, and 2 mg/day zeaxanthin); and 14
in Group 3 (17 mg/day meso-zeaxanthin, 3 mg/day lutein, and 2 mg/day zeaxanthin). The macular pigment optical density
was measured using customized heterochromatic flicker photometry, and visual function was assessed using
corrected distance visual acuity and by letter contrast sensitivity.
There was a statistically significant increase in the macular pigment optical density was observed at all
measured eccentricities in Group 2 (P ≤ 0.005) and in Group 3 (P < 0.05, for all), but only at
1.75° in Group 1 (P = 0.018). Statistically significant (P < 0.05) improvements in letter
contrast sensitivity were seen at all spatial frequencies (except 1.2 cycles per degree) in Group 3, and at low
spatial frequencies in Groups 1 and 2.
The authors concluded that augmentation of the macular pigment optical density across its spatial profile and
enhancements in contrast sensitivity were best achieved after supplementation with a formulation containing high doses
of meso-zeaxanthin in combination with lutein and zeaxanthin.
Sabour-Pickett S, Beatty S, Connolly E, et al. Retina. September 2014, Vol 34, Issure 9, P 1757-1766.
Acute Retinal Necrosis Associated With The Epstein-Barr Virus: Immunohistopathologic Confirmation.
The importance of this study was discovering histopathologic documentation that the Epstein-Barr Virus (EBV) has
been implicated as a cause of Acute Retinal Necrosis (ARN). ARN is a syndrome characterized by progressive,
intraretinal inflammation and necrosis. The most common causes for ARN are Varicella-Zoster Virus (VZV), Type 1 and
Type 2 Herpes Simplex Virus (HSV), and Cytomegalovirus. EBV, a double-stranded DNA virus transmitted by oral
secretion, infects more than 90% of humans. The primary infection is characterized most commonly by
clinical syndromes: fever, pharyngitis, lympohadenopathy, palatal petechiae, hepatomegaly, and splenomegaly. The role
of EBV in ARN is unclear because its seroprevalance in the United States is greater than 90% and PCR detects EBV
in 20% of normal cadaveric eyes. In this case report, the PCR results yielded positive from the vitreous
without detection of DNA from other herpes viruses. Additionally, this is the first case in which EBV was detected
by molecular pathology within retinal cells. Since there was a presence of EBV in the retinal cells, this eliminates
the possibilities that infiltrating lymphocytes were responsible for the positive data.
Schaal S, Kagan A, Wang Y, et al. JAMA Ophthalmology 2014 July; 132(7): 881-882.
Acute Zonal Occult Outer Retinopathy: A Classification Based on Multimodal Imaging.
The importance of this study was to describe the multimodal imaging in a group of patients while showing a distinct
clinical entity that best represented acute zonal occult outer retinopathy (AZOOR). This was a retrospective review of
patients diagnosed with AZOOR at two centers. Forty-eight eyes were assessed and twenty of the patients were female. The
median age of the diagnosis was 47 years old and the mean of the follow-up period was 39 months. AZOOR should be
considered when young patients, mostly females, develop the onset of photopsia in a localized area of the visual field.
The clinical appearance of the AZOOR lesion varied depending on their duration and location. Some characteristics that
the patients presented with throughout the study were demarcating lines of progression at the level of the outer retina
and trizonal patterns of sequential involvement of the outer retina (zone 1), retinal pigment epithelium (zone 2), and
choroid (zone 3). By using spectral-domain OCT, there was significant loss of the ellipsoid line outside of the foveal
region. When using the SD-OCT on these patients, the results also showed thickening of the outer plexiform layer and loss
of the outer nuclear layer temporal to the nerve. Another clinical sign discovery was peripapillary atrophy associated with
the pigmented demarcating line in association with scattered intra-retinal bone spicule pigment clumping and retinal
artery narrowing. Fundus autofluorescence was used which displayed a speckled autofluorescent pattern within the AZOOR
lesion in combination with a hyperfluorescent (demarcation line) continuous around the lesion. The best way to highlight
the trizonal pattern was using the ICG. When using ICG, the outside (zone 1) of the AZOOR lesion was normal, while the
inside (zone 2) showed minimal late extrachoroidal leakage. Hypofluorescence was observed with the absence of leakage of
the ICG molecule into the choroid corresponding to choriocapillaris atrophy (zone 3). Visual fields can only be useful if
the retina is the first thing involved. The disease may be unilateral but throughout the study the second eye was
involved during the follow-up period.
Mrejen S, Khan S, Gallego-Pinazo R, et al. JAMA Ophthalmol 2014 June; 132(9): 1089-1098.
Outer Retinal Corrugations in Age-Related Macular Degeneration.
The Objective of this investigation was to describe a new outer retinal finding of AMD using spectral-domain (SD) OCT
and suggest histopathologic correlates. The study included 25 eye of 16 patients with AMD with severe atrophy due to either
CNV or geographic atrophy and 53 donor eyes of 53 patients with late AMD. Findings in the outer retina were evaluated in
SD-OCT images in eyes with atrophy of the retinal pigment epithelium (RPE) and compared with histopathologic findings in
eyes with GA or CNV that also showed loss of the RPE.
A curvilinear hyper-reflective density was identified above the Bruch's membrane line within the atrophic area in
the SD-OCT images. At the internal border, the material was contiguous with the outer portion of the RPE band. Below
the material was a relatively hyporeflective space. The material was thrown into folds in cases with atrophy following
CNV or was seen as a sheet with numerous bumps in eyes with GA. Review of histopathologic findings of eyes with advanced
GA and CNV revealed a rippled layer of basal laminar deposits in an area of RPE atrophy that was located in the same
level as the curvilinear line seen in the OCT images.
This study described a new entity, termed outer retinal corrugations, which may correspond to histological findings
of basal laminar deposits, extracellular deposits that persist in eyes with late AMD. Observation of this undulating
band does not necessarily mean there is exudation or leakage; as a consequence, these patients do not need treatment
based on this solitary finding.
Ooto, Sotaro; Vongkulsiri, Sritatath; Sato, Taku et. al. JAMA Ophthalmology 2014 Jul; 132 (7): 806-813.
Prevalence of and Risk Factors for Diabetic Macular Edema in the United States.
The objective of this study was to estimate the prevalence of DME in the US population and to identify associated risk factors.
This study conducted a cross-sectional analysis of 1038 participants aged 40 years or older with diabetes and
reviewed valid fundus photographs included in the 2005 to 2008 National Health and Nutrition Examination Survey.
The main goal is to identify the overall prevalence of DME and its prevalence according to age, race/ethnicity, and sex.
Of the 1038 persons with diabetes analyzed for this study, 55 had DME, for an overall weighted prevalence of
3.8% (95% CI) or approximately 746,000 persons in the US 2010 population aged 40 years or older. This
study identified no differences in the prevalence of DME by age or sex. Multivariable logistic regression analysis
showed that the odds of having DME were higher for non-Hispanic blacks than for non-Hispanic whites. Elevated levels
of glycosylated hemoglobin A1c and longer duration of diabetes were also associated with DME prevalence.
The results suggest a greater burden of DME among non-Hispanic blacks, individuals with high levels of hemoglobin A1c,
and those with longer duration of diabetes. Given recent treatment advances in reducing vision loss and preserving
vision in persons with DME, it is imperative that all persons with diabetes receive early screening; this recommendation
is even more important for those at higher risk for DME.
Varma, Rohit; Bressler, Neil; Noan, Doan et al. JAMA Ophthalmol. 2014;132(11):1334-1340.
doi:10.1001/jamaophthalmol.2014.2854.
Sensitivity and Specificity of Spectral-Domain Optical Coherence Tomography in Detecting Idiopathic
Polypoidal Choroidal Vasculopathy.
This retrospective observational case-control study evaluates the efficacy of spectral-domain optical
coherence tomography (SD OCT) compared to indocyanine green angiography (ICGA) in detecting idiopathic
polypoidal choroidal vasculopathy (PCV) and in differentiating between PCV and occult choroidal
neovascularization (CNV).
A masked grader reviewed SD OCTs of 51 eyes of 44 patients who presented with at least 1 pigment epithelial detachments
(PEDs) attributable to either PCV or occult CNV. Qualitative analysis of the SD OCT was done and separated into
three distinguishable appearances: sharp PED peak, PED notch, hyporeflective lumen within hyperreflective lesions adherent
to retinal pigment epithelium. Next, the diagnosis based on SD OCT was compared with the diagnosis made using ICGA
and fluorescein angiography. SD OCT based on the features above detected 35 of 37 true-positive PCV lesions but missed
2 ICGA-confirmed lesions (false negatives). SD OCT correctly excluded 13 of 14 non-PCV lesions but misidentified 1 PCV
lesion (false positive). These data showed a sensitivity of 94.6% and a specificity of 92.9% for the above SD
OCT features in identifying PCV lesions.
Therefore, SD OCT allows for good detection of PCV and differentiation between PCV and occult CNV. This may decrease the
need for ICGA and the risks related to this procedure.
Salvo G, Vaz-Pereira S, Keane P. American Journal of Ophthalmology Volume 158, Issue 6, Pages 1228–1238.e1, December 2014.
Concentric Macular Rings Sign in Patients With Foveal Hypoplasia.
This study describes concentric macular rings sign found on infrared reflectance (IRR) images in patients with
foveal hypoplasia. Investigators studied 13 patients with foveal hypoplasia (7 with ocular albinism [OA],
5 with oculocutaneous albinism [OCA], and 1 with aniridia) at a tertiary ophthalmology center from February 2009,
through April 2013. All patients and an age-matched control participant underwent a complete clinical
examination, electroretinography (full field and pattern), visual evoked potentials, fundus autofluorescence
IRR, and OCT.
Thirteen patients (6 girls and 7 boys), with a mean age of 5.8 years (range, 3-11 years), were included in the study.
Seven patients were diagnosed as having OA and had minimal clinical signs (fine nystagmus in 2 patients and subtle
iris transillumination in 5 patients). Five patients with OCA and 1 with aniridia were also included. In 12 patients,
OA and OCA were confirmed with 5-channel visual evoked potentials (optic nerve misrouting). Whenever OCT was
performed, foveal hypoplasia was indicated by the lack of foveal dip. The macula lacked the foveal attenuation
normally seen with fundus autofluorescence, and a concentric macular rings reflex was seen with IRR in all 13 patients
and with GDx VCC in 1 patient. A normal bowtie reflex was seen with IRR and GDx VCC in the age-matched control participant.
Findings suggest that concentric macular rings seen on IRR or GDx VCC can occur in patients with foveal hypoplasia and
can therefore aid in the diagnosis, especially in patients with minimal clinical signs (mild OA) or in cases in which
OCT cannot be performed (young patients or patients with high-amplitude nystagmus).
Cornish, K, Reddy, A, McBain,V. JAMA Ophthalmol. 2014;132(9):1084-1088. doi:10.1001/jamaophthalmol.2014.1715.
ANSWER
TO "YOU MAKE THE DIAGNOSIS"
This patient presented with optic nerve atrophy, foveal hypoplasia sclerotic vessels, inactive retinal
neovascularization, retinal detachment and retinoschisis associated with incontinentia pigmenti.
This condition, which has a variety of dermatological, dental, ocular and neurological abnormalities,
is also known as Bloch-Sulzberger Syndrome. Incontinentia pigmenti is a rare, congenital,
multi-system varied disease affecting the ectodermal structures which presents shortly after birth.
Our patient's visual acuity was hand motion at 5 feet in the affected left eye with a 3+ afferent
pupillary defect. Differentials of this condition should include retinopathy of prematurity,
familial exudative vitreoretinopathy, sickle-cell disease and X-linked retinoschisis.
The genetics of this condition have been reported as both X-linked dominant trait and spontaneous
mutation. Our patient was genetically tested in infancy and found to have a spontaneous mutation.
Roughly 80% of IP cases are caused by a deletion of exons 4-10 on the nuclear factor (NF)-κB
essential modulator (NEMO) gene.This gene is involved in the regulation of inflammation and
apoptosis. Female infants survive due to a skewed X-inactivation, whereas it is lethal in males
in utero. Four dermatological stages exist following the lines of Blaschko. The stages do not all
have to occur and several may overlap simultaneously. Diagnosis is made by skin biopsy.
The stages are listed as the following:
Stage 1: erythema and vesicular lesions (90-95%)
Stage 2: plaques and papules (70%)
Stage 3: linear or whorl hyperpigmentation (90-98%)
Stage 4: hypopigmentation and scarring (30-75%)
Other ectodermal structures that may be involved include the following: Hair 38%, nails 7%, dental
65%, neurological 30% and ocular 35%. Upon further questioning and evaluation, our patient revealed a
small area of alopecia on right side of head, hypopigmentation and scarring of the skin on all four limbs and
dental implants to cosmetically correct her dental abnormalities associated with the condition.
Ocular manifestations are often unilateral, and asymmetrical if bilateral. Documented ocular pathology include:
temporal retina avascularity, neovascularization, vitreal hemorrhage, total hyphema, RPE mottling, preretinal
gliosis, retinal detachment, foveal hypoplasia, dragged fovea, and optic nerve atrophy. Laser coagulation or cryotherapy
of the avascular retina can help prevent progression of vasculopathy and retinal detachment but with mixed results.
Lin et al. reports while limited trials of Anti-VEGF therapy show promise in the treatment of pediatric vitreoretinopathies,
more controlled trials are required to establish safety and efficacy standards as well as dosing regimen.
REFERENCES
1. Agarwal A. 2012. Gass' atlast of macular disease. 5th ed. Nashville, TN. Elsevier Inc. pp. 578-583
2. Poziomczyk CS, et al. Incontinentia pigmenti. An Bras Dermatol 2014:89(1):26-36
3. Carney RG. Incontinentia pigmenti, a world statistical analysis. Arch Dermatol 1976 112:535-42
4. Holmstrom G, Thoren K. Ocular manifestations of incontinentia pigmenti. Acta Ophthalmol Scand 2000:78:348-353
5. Wong G, Willoughby CE, Parslew R, Kaye SB. The importance of screening for sight-threatening retinopathy in incontinentia pigmenti. Pediatr Dermatol 2004:21(3)242-245
6. Lin KL, Hirose T, Kroll AJ, Lou PL, Ryan EA. Prospects for treatment of pediatric vitreoretinal diseases with vascular endothelial growth factor inhibition. Semin Ophthalmol 2009:24(2):70-6
Jane Ann Grogg, O.D., ORS Fellow, and
Hin Cheung, O.D., Ocular Disease Resident, Indiana University School of Optometry
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IN THE
NEWS
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Actavis Acquires Allergan For Approximately $66 Billion
The healthcare community has been watching the Valeant Pharmaceuticals-Allergan deal closely over
the last few months, but that has come to an end with Irish pharmaceutical company Actavis
acquiring Allergan for approximately $66 billion, or $219 per Allergan share.
The companies entered into a definitive agreement under which Actavis will acquire Allergan for a combination
of $129.22 in cash and 0.3683 Actavis shares for each share of Allergan common stock. According to the
companies, the deal will create one of the top 10 global pharmaceutical companies by sales revenue, with
combined annual pro forma revenues of more than $23 billion anticipated in 2015. The transaction has been
unanimously approved by the Boards of Directors of Actavis and Allergan and is supported by the management
teams of both companies.
"Today's transaction provides Allergan stockholders with substantial and immediate value, as well as
the opportunity to participate in the significant upside potential of the combined company," says Allergan
CEO David E. I. Pyott. "We are combining with a partner that is ideally suited to realize the full
potential inherent in our franchise. Together with Actavis, we are poised to extend the Allergan growth story
as part of a larger organization with a broad and balanced portfolio, a meaningful commitment to research
and development, a strong pipeline, and an unwavering focus on exceeding the expectations of patients and
the medical specialists who treat them."
Following the completion of the acquisition, the combined company will be led by Brent Saunders, CEO and
president of Actavis, and Paul Bisaro will remain executive chairman of the board. The integration of the
two companies will be led by the senior management teams of both companies, with integration planning to
begin immediately in order to transition rapidly to a single company. Additionally, two members of the
Allergan Board of Directors will be invited to join the Actavis Board of Directors following the completion of
the transaction.
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Valeant Acquires Nicox Inc. For Up To $20 Million In Cash, Future Payments
Valeant Pharmaceuticals has acquired Nicox's U.S. diagnostics subsidiary Nicox Inc. in a deal totaling up to
$20 million, Nicox announced in a press release.
Under the terms of the agreement, Valeant acquired Nicox Inc. for $10 million in cash, plus additional
cash payments of up to $10 million based on Valeant achieving sales benchmarks with transferred products.
The deal is effective immediately.
Nicox's operations outside the U.S. and the company's recent purchase of Aciex Therapeutics will not be affected
by the acquisition, the release said. Nicox acquired Aciex in October.
Valeant has acquired most of Nicox's commercial infrastructure in the U.S. associated with diagnostics; Nicox
has retained a cadre of U.S.-based employees focused on therapeutics.
"The decision to focus on therapeutics is due to several recent and short- to mid-term opportunities under
advanced discussions. This strategic move with our long-standing partner Valeant will enable us to
leverage resources for our growing pipeline of advanced drug candidates," Michele Garufi, CEO of Nicox,
said in the release.
AC-170 for allergic conjunctivitis, the first product from the Aciex pipeline, is scheduled for launch in the
U.S. in 2016, contingent on U.S. Food and Drug Administration approval.
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Ophthotec Reports $39.6 Million Revenue In Third Quarter
Ophthotec reported $39.6 million in revenue in the third quarter, as well as a 9-month net loss of $62.3
million, according to a company press release.
The revenue was attributed to a $50 million enrollment-based milestone reached in September through an
agreement with Novartis to research Fovista anti-PDGF therapy for wet age-related macular degeneration in
a phase 3 clinical trial program. The milestone payment was recorded as deferred revenue.
At the end of the third quarter, Ophthotec reported having $408.8 million in cash, cash equivalents and
marketable securities.
Research and development expenses were $17.1 million in the third quarter, compared with $11.1 million in the
third quarter of 2013. This increase is also attributable to the Fovista phase 3 clinical program, according
to the release.
As of September 30, the company reported a 3-month net income of $10.9 million, or $0.31 per diluted
share, compared with a net loss of $18.4 million, or $10.26 per diluted share for the same quarter in 2013.
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ONL Therapeutics Awarded NEI Grant To Develop Treatment For Retinal Disease
The National Eye Institute awarded ONL Therapeutics a $1.37 million grant to develop ONL101, a first-in-class
small molecule peptide designed to protect photoreceptors in retinal detachment, according to a press release.
ONL101 was previously given orphan drug designation for retinal detachment.
The Small Business Innovation Research (SBIR) phase 2 contract will be used to support the conclusion
of preclinical development stages required for an investigational new drug application. The grant follows
a phase 1 SBIR project that focused on the feasibility of blocking photoreceptor apoptosis in animal models
of retinal detachment.
"Illustrating this mechanism of photoreceptor protection not only helps advance ONL101 as a treatment for
retinal detachment but also provides rationale for the technology's application to other important retinal
diseases such as wet and dry age-related macular degeneration," John Freshley, CEO of ONL Therapeutics,
said in the release.
The company expects to submit an investigational new drug application in late 2015 to start a phase 1
clinical trial of ONL101 in retinal detachment.
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Serum Soluble Flt-1 May Be Biomarker For Neovascular AMD
Serum soluble Flt-1 may be a biomarker for the development of neovascular age-related macular
degeneration, according to study findings in the American Journal Of Ophthalmology.
Researchers analyzed 56 subjects without AMD, 53 subjects with early AMD and 97 subjects with neovascular
AMD and measured serum soluble Flt-1 (sFlt-1) concentrations from each subject.
Mean serum sFlt-1 concentration was 90.8 pg/mL for non-AMD, 88.2 pg/mL for early AMD and 79.9 pg/mL for
neovascular AMD. Neovascular AMD subjects had significantly decreased sFlt-1 compared with non-AMD and early
AMD subjects (P < .01).
The odds of having neovascular AMD decreased by 27.8% based on each 10-point increase in sFlt-1.
Serum sFlt-1 less than 80 pg/mL among subjects older than 73 years was associated with a greater risk
of neovascular AMD.
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AMD Severity In First Eye Foretells Incidence, Progression In Fellow Eye
Severity of age-related macular degeneration in one eye was associated with an increased incidence of disease
and progression in the fellow eye, according to a study in JAMA Ophthalmology.
Researchers analyzed data from 4,379 patients included in the Beaver Dam Study. Each patient underwent
retinal photography at baseline and at up to four subsequent follow-up visits. They were also genotyped.
After adjusting for age, sex and the Y402H polymorphism in the complement factor H gene on chromosome 1q,
the researchers utilized the Wisconsin Age-Related Maculopathy Grading System on the retinal photographs to
assess the incidence, progression and regression of AMD, and assessed mortality, as well.
Results showed more severe AMD in one eye correlated with a higher incidence of AMD and rapid progression in
the fellow eye. Similarly, less severe AMD in one eye correlated with less progression in the fellow eye,
according to the researchers.
The researchers estimated that 51% of the participants who developed any AMD would always maintain AMD
severity states within one step of the other between eyes, and that 90% of the participants would stay
within two steps.
Relationships between severity of AMD in the fellow and age, gender or complement factor H Y402H genotype
were insignificant, according to the researchers.
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FDA Grants Priority Review To Lucentis For Diabetic Retinopathy
The U.S. Food and Drug Administration has granted priority review of Lucentis for the treatment of
diabetic retinopathy, according to a Genentech press release.
The company's supplemental Biologics License Application was submitted on Aug. 7, 2014, based on results
from the RISE and RIDE phase 3 trials, and an action date of Feb. 6, 2015, has been scheduled.
If approved, Lucentis (ranibizumab) could be the first eye medication made available to patients with
diabetic retinopathy, according to the release.
The injection was the first FDA-approved agent for treatment of diabetic macular edema in August 2012.
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Quarterly Net Revenue Increases To $2.4 Million For Alimera
Alimera Sciences reported $2.4 million in net revenue in the third quarter, a 211% increase from $760,000
in the third quarter of the previous year, according to a press release.
The company attributed the increase to higher use of Iluvien (fluocinolone acetonide intravitreal implant)
in Germany and the United Kingdom.
GAAP net loss totaled $7 million, compared with $1.1 million a year ago. GAAP loss per share was $0.17 per
share, compared with $0.04 a year ago.
GAAP cost of goods sold increased approximately 517%, totaling $370,000 compared with $60,000 in the
third quarter 2013.
The company expects to begin delivery of Iluvien to retina specialist in the U.S. in the first quarter of 2015.
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Thrombogenics Reports €12.2 Million Loss Between Second, Third Quarters
ThromboGenics reported cash and investments totaling €136.6 million at the end of the third quarter,
down from €148.8 million at the end of the second quarter.
However, according to a press release, the company is optimistic that cash flow and revenues will reach
targets in the near term.
"ThromboGenics remains on track to achieve its target of profitability in the U.S. by 2016, based on Jetrea
sales of around €30 million," the release said. "The company is also targeting to become cash flow
positive by 2017 and to achieve total revenues of €100 million by 2019."
According to the release, the company is devoting significant resources to the development and marketing of ocriplasmin.
"ThromboGenics believes that it has the financial resources it needs to fully sustain the U.S. commercialization
of Jetrea, to research and develop new indications and formulations of Jetrea for the U.S. market, and to
expand its R&D pipeline and further broaden its commitment to become a leading ophthalmology company,"
the release said.
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MEET
THE PRESIDENT
In each issue, a Fellow of the Optometric
Retinal Society is highlighted. In this issue, Dr. Brad M. Sutton, incoming President of the
ORS, will be highlighted for the second time.
Dr. Brad Sutton received his Bachelor of Arts degree in Psychology from Indiana University in 1989 and
his Optometry Doctorate from IU in 1993. Upon graduating, he accepted a one-year residency in
Ocular Disease and Surgical Co-management at Omni Eye Services in Memphis, Tennessee, where he
remained with the center as its director from 1994 to 1999. In November of 1999 he returned to IU to
become the clinic director at the Indianapolis Eye Care Center. He is heavily involved in patient
care, clinical teaching, administration, and lecturing in the ocular disease courses.
Dr. Sutton's main areas of clinical interest include ocular disease and surgical management. He has
given more than one-hundred-twenty-five continuing education lectures on topics related to ocular disease
at the local, state, national, and international level. Dr. Sutton was named the Young Optometrist of
the Year for the state of Tennessee in 1997-1998 and received the same award (President's Citation)
for the state of Indiana in 2001.
He currently serves as the President of the Optometric Retina Society (ORS).
He loves sports and is a rabid Colts, Hoosiers, and Pacers fan. He enjoys hiking, playing tennis,
reading, and spending time with his children. He is also an active member of the board of directors
of the Indianapolis Zoo.
WHY
BECOME AN ORS MEMBER?
By Rex Ballinger, O.D., F.A.A.O.
Chair, Membership Committee
Membership in the Society can provide several benefits. You may
receive discounts at annual meetings. You’ll receive regular
newsletters on new and exciting updates on retinal disease diagnosis
and management as well as other newsy items of interest. And you’ll
be associated with a body of knowledge and resources which can
help you in many other ways. So consider membership in the Society.
It will be worth your while in your quest for better understanding
of the retina.
If your interests extend beyond the general, if you want to become
part of the dynamic team involved in the Society to share your
interest and enthusiasm with your colleagues, consider becoming
a Fellow member. Details and applications can be found at
www.optometricretinasociety.org |
SPONSOR NEWS
Editor
in Chief
Steven Ferrucci, OD, FAAO
Co-Editor
Mark T. Dunbar, OD, FAAO |
Journal
Reviewers
Tahrim Rahman, OD
Kristie Draskovic, OD
Savannah Brunt, OD
Nicholas Zagorianos, OD
Art/Production Director
Joe Morris
|
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