Volume 10, Number 3
December 2014
 

 

Inside This Issue  



 
FROM THE DESK OF THE EDITOR
 
YOU MAKE THE DIAGNOSIS
 
CLINICAL PEARLS
 
JOURNAL ABSTRACTS
 
IN THE NEWS
 
SPONSOR NEWS
 
This e-newsletter is provided free to doctors through industry support from
 

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:

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

 

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


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

Figure 1: Fundus Photos OS

Figure 2: Left eye reveals foveal hypoplasia, shallow foveal contour, and displaced foveal position towards the optic nerve.

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.




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



 

IN THE NEWS

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.

 

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.

 

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.

 

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.

 

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.

 

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.

 

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.

 

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.

 

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.

 



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

 

 

 
Review of Optometry® is published by the Review Group, a Division of Jobson Medical Information LLC (JMI), 11 Campus Boulevard, Newtown Square, PA 19073.

To subscribe to other JMI newsletters or to manage your subscription, click here.

To change your email address, reply to this email. Write "change of address" in the subject line. Make sure to provide us with your old and new address.

To ensure delivery, please be sure to add revoptom@lists.jobsonmail.com to your address book or safe senders list.

Click here if you do not want to receive future emails from Review of Optometry.