Untitled Document

  Volume 15, Number 3
September 2019


Inside This Issue 

This e-newsletter is provided free to doctors through industry support from


It’s been a long few weeks for me getting into the groove of a new routine post-maternity leave. Taking that four-month break from Optometry really puts into perspective how quickly the field is changing. While those advancements are exciting, it is also overwhelming to keep up with it all in the limited free time you have outside of patient care. Even though I am a fellow in a retina-focused group, I don’t just take care of retinas all day long. Like the majority of ODs, my setting is truly primary care focused. So although some days I would just like to focus on my interests in the posterior segment, I have to stay up-to-date on a little bit of everything including…eeek contact lenses and dry eye. So I appreciate the email updates that I get from resources like Review of Optometry to keep me in the loop, even if it that means my email inbox is always full. So please read on in this newsletter and check “getting up-to-speed on the posterior segment” off your to-do list. There may be a few glaucoma tidbits hidden in. But I can promise no contact lens tips (not from me at least).

Speaking of education and staying up-to-date, the next ORS annual meeting, Retina Update 2019, is just a few months away on Dec. 6 and 7 in Scottsdale, Ariz. Twelve CE hours will be offered focusing on the latest in posterior segment disease provided by some of the ORS’s top notch experts in retina. For more information or to register, please visit https://web.cvent.com/event/a247de90-c219-4898-a822-bc8d6f108d69/summary. Hope to see you there!

Anna Bedwell, OD, FAAO



Another summer has come and is mostly gone, and fall is almost here. I certainly miss summer, but I look forward to fall and, here in the southwest, I’m grateful for the relenting of the scorching summer heat. Autumn brings the beautiful fall colors to most of the country. Here in the desert, our mostly brown landscape just turns more brown with rare displays of the wonderful fall colors so abundant in other parts of the country. As I look at the beautiful foliage change in other areas, I’m reminded of how amazing our retinas are at capturing all of those fantastic colors and letting us enjoy the show nature puts on. It always amazes me that within that little tiny thin layer of the eye that we call the retina are all of the receptors and connections that allow color to be part of our experience. Color perception is only one of the many amazing things that our eyes capture as part of “vision.”

I’m grateful for all of the research that is done in respect to the eye and vision. That research spans the gamut from refractive error management to glaucoma and to blinding genetic retinal diseases. I feel that it is imperative for each of us to remain abreast of the ongoing research so that we can inform our patients of breakthroughs that might help to retain their precious vision or, at the very least, give them hope that new treatments are possible in the future. I think of how drab life would be without color vision for me to appreciate and enjoy the beauty around us, but how much worse it would be without vision at all.

I thank Dr. Anna Bedwell, our editor of this newsletter for helping to keep us up to date with timely article reviews and news of current retinal studies. Please share this newsletter with your colleagues so they can better stay up to date on retinal issues. I hope you all have a great autumn and enjoy the colors.

Jeffrey Austin, OD, FAAO
ORS President


Answer appears later in newsletter.

Answer appears later in newsletter.


Image Gallery

Which of the following images represents a melanocytoma?

Answer appears later in the newsletter.



Developing Prognostic Biomarkers in Intermediate Age-Related Macular Degeneration: Their Clinical Use in Predicting Progression

This review article from Australia examined a fascinating premise. What if OCT could not only be utilized to examine the current state of intermediate macular degeneration in an eye, but also contained prognostic clues that could help to predict the risk of future progression to geographic atrophy or neovascularization? In examining the available literature, the researchers found the following OCT features to be predictive of an increased risk of progression to advanced disease. 1) Hyper-reflective foci: These reflective dot-like structures are intra-retinal and are located at the apex of drusen. They are believed to be associated with focal pigmentary abnormalities, and are linked with a five-fold risk of progression to geographic atrophy in two years. 2) Reticular Pseudodrusen: These lacy, subretinal drusenoid deposits are located under the neurosensory retina but above the RPE. They are associated with a two- to six fold increase in progression to advanced AMD. 3) Nascent geographic atrophy: This finding consists of outer retinal collapse with a hyporeflective wedge and intact underlying RPE. It is usually found within 1,500 microns of the center of the fovea and is very strongly associated with impending geographic atrophy. 4) Sub-RPE hyperreflective columns: These linear columns represent increased signal strength / reflectivity in the choroid below an area of seemingly intact RPE. They are believed to be seen where are there are subclinical areas of damaged RPE, and they may precede both geographic atrophy and neovascular disease. 5) Drusen with subretinal fluid: This finding consists of subretinal fluid adjacent to conglomerated drusen in the absence of clinically evident CNV. The fluid does not extend higher than the peak of the adjacent drusen. It is believed that the fluid may represent subclinical CNV. 6) Drusen substructures: Normally, the reflectivity of drusen is homogenous in a given eye. When there is substantial variation and heterogeneity in the reflectivity of the drusen, this may be a sign of impending geographic atrophy. 7) Drusen regression: Fifty percent of eyes with intermediate AMD exhibit regression of drusen over a two-year period. This is believed to be a direct precursor event that strongly predicts progression to geographic atrophy or neovascularization.

Ly A, Lapp M, Nivison-Smith L, et al. Developing prognostic biomarkers in intermediate age-related macular degeneration: their clinical use in predicting progression. Clinc Ex Optom 2018;101:172-81.


Association of Dietary and Supplemental Calcium Intake With Age-related Macular Degeneration: Age-Related Eye Disease Study Report 39

Past literature reports have provided conflicting information regarding calcium intake and the risk of AMD development or progression. The National Eye Health and Examination Survey found increased calcium intake to be associated with AMD diagnosis. The Blue Mountain Eye Study, on the other hand, found decreased calcium intake to be associated with late / advanced AMD. The purpose of the current report from the AREDS study group was to evaluate the effect of dietary and supplemental calcium on the development of AMD, progression to intermediate AMD, and progression to geographic atrophy or neovascular disease. It included 4,751 patients from the original AREDS cohort.

The study concluded that patients who took the highest levels of supplemental calcium were less likely to develop advanced / late AMD than were patients who took the lowest amount of supplemental calcium. However, those same patients were not less likely to develop intermediate AMD.

While it seemed promising that increased calcium intake was associated with a decreased rate of advanced AMD, the authors pointed out that increased calcium intake in the study was highly associated with increased lutein intake. This could certainly be a confounding factor, and the authors also surmised that increased calcium intake might simply be a surrogate marker for better overall health habits. At this time, they did not recommend a change to current clinical management protocols regarding calcium supplements in patients with AMD.

Tisdale AK, Agrón E, Sunshine SB, et al. Association of dietary and supplemental calcium intake with age-related macular degeneration: Age-related eye disease study report 39. JAMA Ophthalmol. 2019; Mar 21. [Epub ahead of print].

A Deep Learning Algorithm to Quantify Neuroretinal Rim Loss from Optic Disc Photographs

Glaucoma is a leading cause of irreversible blindness worldwide. Reasons for detection hindrance include poor public and lack of visual symptoms until late in the disease. For the past several decades, clinicians analyzed photographic images in screening for diabetic retinopathy (DR). However, manual review of disc photographs is not only time-consuming, but also highly subjective the authors say.

Numerous studies document the fair inter-rater reliability even among fellowship-trained glaucoma specialists. Even artificial intelligence (AI) may suffer the same outcome given the reference standard images being subjectively graded and inputted. The authors proposed that quantitative data derived from structural measurements of the optic nerve head might provide a better reference standard for development of deep learning (DL) neural networks than qualitative gradings of the optic disc on fundus photographs. For this, the authors used the minimum rim width relative to the Bruch’s membrane opening (BMO-MRW), which they said might be particularly sensitive for the identification of early glaucoma and glaucoma suspects.

A total of 9,282 pairs of optic disc photographs and SD-OCT optic nerve head scans from 927 eyes of 490 subjects were randomly divided into the validation plus training (80%) and test sets (20%). A DL convolutional neural network (CNN) was trained to predict the SD-OCT BMO-MRW global and sector values when evaluating optic disc photographs. The predictions of the DL network were compared to the actual SD-OCT measurements. The area under the receiver operating curve (AUC) was used to evaluate the ability of the network to discriminate glaucomatous visual field loss from normal eyes. The authors used ResNet—a deep residual network that allows for relatively rapid training of very deep CNNs.

From this study, the authors developed and validated a novel DL CNN capable of quantifying the amount of neuroretinal damage on an optic disc photography. They cited several advantages of using the BMO-MRW parameter such as its objectivity, high reproducibility and accuracy for glaucoma diagnosis, and ability to judge the optic nerve in situations where it is difficult to grade.

Thompson A, Jammal A, Medeiros F. A deep learning algorithm to quantify neuroretinal rim loss from optic disc photographs. Am J Ophthalmol. 2019;201:9-18.

Efficient Deep Learning-based Automated Pathology Identification in Retinal Optical Coherence Tomography Images

According to the authors, the emergence of deep learning (DL) brings new methods and ideas to the classification of retinal optical coherence tomography (OCT) images, especially the development of the convolutional neural network (CNN) and its important impact on image classification. The CNN makes it possible to process images in the form of pixels as input and to give the desired classification as output, which can avoid the complicated feature extraction in the traditional algorithm. The authors noted that CNN was widely used in computer vision (especially in image classification) since the ImageNet competition in 2012. In recent years, variants of CNN architectures have been developed, such as AlexNet, GoogLeNet and ResNet.

A majority of the previous works on the retina focused on the methods of retinal layer segmentation. All of these approaches mainly consisted of two components, namely extracting features and training classifiers. To address the problem of insufficient training data and time-consuming propagation, the authors proposed a method for automatic diagnosis of AMD, DME and normal (NOR) in retinal OCT B-scans that can effectively identify different pathologies.

Their approach consisted of three parts: Preprocess the OCT B-scans to reduce the morphological variations, apply a pre-trained Inception V3 architecture on each OCT B-scan to extract its middle-level features automatically and train the CNN to extract the semantic level features of OCT B-scans for image classification.

In doing so, the authors produced an algorithm that was an effective method for retinal OCT detection and was a potentially impactful tool for computer-aided diagnosis and screening of ophthalmic diseases.

Qingge J, He W, Huang J, et al. Efficient deep learning-based automated pathology identification in retinal optical coherence tomography images. Algorithms. 2018;11(6):1-12.

Evaluation of a Deep Learning Image Assessment System for Detecting Severe Retinopathy of Prematurity

For infants who do undergo retinopathy of prematurity (ROP) screening, accurate ROP diagnosis is difficult and requires identification of three parameters (zone, stage and plus disease), which are combined into a composite diagnostic category. Prior work has demonstrated the near-perfect accuracy of a deep learning (DL) retinal image analysis for diagnosing plus disease in ROP, according to the authors. DeepROP - developed by the Imaging & Informatics in ROP (i-ROP) research consortium – has been incorporated into a system termed ‘i-ROP DL’. However, the system was trained only to recognize plus disease. In this study, the authors investigated the overall clinical and public health applicability of this system by assessing its ability to identify broader diagnostic categories of ROP, as well as overall disease severity, from posterior pole images alone.

Key findings included: (1) Despite only being trained to recognize plus disease, the i-ROP DL system accurately detected clinically significant ROP, with 94% sensitivity for type 1 ROP; (2) the i-ROP DL vascular severity score was strongly correlated with expert ranking of overall disease severity; and (3) the system detected severe ROP based only on posterior pole vascular morphology, emphasizing the collinearity of diagnostic parameters in ROP.

The authors acknowledged several study limitations including the clinician variability in ROP diagnosis and the image quality of data it presents to the AI. Also, the definition of clinically significant ROP is a composite of type 2 ROP, type 1 ROP and pre-plus disease. According to the authors, the justification for including pre-plus in this category was that the concept of pre-plus was not introduced until 2005 after the definition of type 2 ROP was established. Pre-plus disease has since been shown to be a strong independent risk factor for progression of disease and, thus, should necessitate referral for specialist examination.

Redd T, Campbell J, Brown J, et al. Evaluation of a deep learning image assessment system for detecting severe retinopathy of prematurity. Br J Ophthalmol. 2019;103:580-4.

Disorganization of the Retinal Inner Layers as a Prognostic Factor in Eyes with Central Retinal Artery Occlusion

A central retinal artery occlusion is a debilitating disease, and, currently, there are no reliable methods to predict visual outcomes or the best treatment strategies. This retrospective study investigated 28 patients who presented to the ophthalmology department following a CRAO and studied multiple parameters including age, reference time to the clinic, mean macular thickness, the change in macular thickness and the disorganization of inner retinal layers (DRIL) to determine prognostic factors for a CRAO.

Patients were treated with ocular massage, anti-glaucomatous agents, anti-platelet aggregating agents, and underwent hyperbaric oxygen therapy sessions until VA was stable. Spectralis SD-OCT was used to measure macular thickness (MT) at five separate points and to determine a DRIL score. DRIL was defined as “the inability to identify any boundaries between the ganglion-cell inner plexiform layer complex, inner nuclear layer, and outer plexiform layer.” It was measured at seven different points and a point was considered positive if DRIL greater than 500 microns was apparent. A score of 0-7 was then assigned.

Results concluded that age could not be used as a prognostic factor, while reference time, MT and DRIL scores all could. Specifically, lower DRIL scores were associated with better final VA, a greater positive change in VA from first exam to last exam and a thicker final MT. Other studies have found that DRIL scoring can be a useful prognostic factor in macular swelling due to diabetes, uveitis, retinal venous occlusions and idiopathic epiretinal membranes. This was the first study to investigate DRIL scores in retinal arterial occlusions, and although further studies with larger samples are needed, it appears the DRIL scoring could be a valuable prognostic tool for patients who have suffered a CRAO.

Yilmaz H, Durukan AH. Disorganization of the retinal inner layers as a prognostic factor in eyes with central retinal artery occlusion. In J Opthalmol 2019; 12(6):990-5.

Effect of Optic Disc-Fovea Distance on the Normative Classifications of Macular Inner Retinal Layers as Assessed With OCT in Healthy Subjects

It has been found that glaucomatous damage can be assessed by careful study of the ganglion cell-inner plexiform layer (GCIPL) thickness in addition to the retinal nerve fiber layer (RNFL) thickness. However, multiple factors including age, gender, axial length and optic disc area are all associated with variability in thicknesses of macular inner layers. It is unknown how these factors influence the performance of the OCT software that provides normative data. This goal of this study was to determine if the distance between the optic disc center and the fovea (DFD) influenced the normative classifications based on thickness measurements of macular inner retinal layers in healthy subjects.

A full ophthalmic examination was performed on 193 Chinese healthy subjects and included visual field testing, a manual measurement of DFD, disc-fovea angle based on fundus photographs, and a Topcon 3D OCT of the macular RNFL (mRNFL), GCIPL and GCC layers (mRNFL + GCIPL). Superior, inferior and total thickness of these layers were recorded, as well as their classifications (green=within normal limits, yellow=below P5, red=below P1).

After adjusting for multiple covariants, it was found that DFD correlated negatively with all the thicknesses of the macular inner retinal layers and eyes that classified as abnormal by at least one parameter had a significantly greater DFD than those classified as normal. The authors speculated that abnormal mRNFL measurements in eyes with a greater DFD was due to the OCT scan area being farther from the disc where the RNFL is thinner. They further speculated that abnormal GCIPL thickness could have been due to stretching of the posterior fundus. This study was limited in that only Chinese subjects were included, and the results only applied to one OCT device. However, it demonstrated that DFD did have an impact on macular thickness and should be considered when analyzing an OCT for glaucomatous damage.

Qiu K, Chen B, Yan J, et al. Effect of optic disc-fovea distance on the normative classifications of macular inner retinal layers as assessed with OCT in healthy subjects. Br J Opthalmol 2019; 103:821-5.





Introduction: Focal choroidal excavation (FCE) is an excavation of the choroid detected by optical coherence tomography (OCT) that can be found in a congenital or acquired form and in a conforming (excavation occupied with outer retinal tissue) or non-conforming (excavation occupied with sub-retinal fluid) subtype. FCE is usually stable and asymptomatic with patients not requiring any treatment. Recently, however, associations with pachychoroidal diseases such as polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSCR) have been recognized; thus, necessitating lifelong monitoring and possible treatment.1

Case Report: A 27-year-old white female presented for a comprehensive eye exam. Best-corrected visual acuity was 20/20 OD and OS. External examination, entrance testing and slit-lamp examination were unremarkable. IOPs were 14 mmHg OD/OS with Goldmann applanation tonometry. The macula OS revealed faint retinal pigmentary changes. OCT through the pigmented changes revealed focal choroidal excavation OS without overlying fluid. OCT-A was unremarkable with no evidence of a CNVM. She was diagnosed with conforming FCEs OS. The patient continues to be monitored annually.

Discussion: FCE is a condition of unknown etiology that is classified as non-conforming (fluid between the photoreceptor layer and the retinal pigment epithelium) or conforming (fluid is lacking). Recently, cases in the literature have revealed increased choroidal thickness (pachychoroid) in patients with FCE, putting it in the pachychoroid spectrum along with pachychoroid pigment epitheliopathy (PPE), CSCR and PCV.1,2 It is postulated that dilated large choroidal vessels (pachyvessels) compress the choriocapillaris causing ischemia and atrophy of the inner choroid leading to FCE.1 Further thickening then leads to RPE damage and the possible development of conditions such as CSCR and CNVMs. Treatment options for conforming FCE is monitoring with proper patient education on possible progression and visual changes. For non-conforming FCE options, include monitoring for self-resolution. In the presence of a CNVM, options include anti-VEGF injections;1,2 however, the data set is limited due to the rarity of the condition.

Raman Bhakhri, OD
ORS Fellow

1. Chung H, Byeonsh SH, Freund KB. Focal choroidal excavation and its association with pachychoroid spectrum disorders: A review of the literature and multimodal imaging findings. Retina. 2017;37:199-221.
2. Lee CS, Woo SJ, Kim YK, et al. Clinical and spectral-domain optical coherence tomography findings in patients with focal choroidal excavation. Ophthalmology.



Eylea Prefilled Syringe Arrives

The FDA recently approved aflibercept (Eylea) prefilled syringe. The 2mg single-dose syringe requires fewer preparation steps compared to vials. It can be used to treat wet age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema (DME) and diabetic retinopathy.

Pollution Alert

The electric vehicle (EV) industry will certainly be interested in the results of this recent study. According to researchers, high-level exhaust exposure may rev up the risk for age-related macular degeneration (AMD). In a report of almost 40,000 Tiawanese citizens, the authors found that high levels of exhaust could nearly double the risk for the disease.


Improving Retinal Laser in Resource-poor Countries

The quality improvement of laser treatment (QUILT) is a new retinal laser simulation system for training in resource-poor countries. There exists a significant risk of loss of vision from inadequate laser treatment despite successful eye screening and detection of sight-threatening diabetic retinopathy. QUILT is a novel laser photocoagulation simulator that contains modules for laser treatment of PDR, diabetic macular edema, retinal vein occlusion and laser retinopexy. The primary objective of the QUILT simulation is to introduce a new bespoke application to support practical skills training in retinal laser treatment in countries where laser training is suboptimal for ophthalmologists and trainees/residents.


Novartis Signs Option Agreement with Iconic Therapeutics

Novartis recently made an upfront payment and an equity investment in Iconic Therapeutics. Novartis is evaluating Iconic’s anti-Tissue Factor monoclonal antibody ICON-4 as a potential therapeutic for AMD, aiming to begin clinical trials in 2020. Iconic sees Tissue Factor as the first disease-modifying agent for AMD.

Nidek Launches the Mirante Multimodal Device

Fitting with the name meaning “overlook,” the newly launched Mirante device and its multimodal platform will allow clinicians to view high-definition SLO and OCT images, along with FA, ICG and ultrawidefield (163 degrees with the optional widefield adapter). The machine acquires OCT images at a maximum area of 16.5mm x 12mm. It also offers options for AngioScan OCT angiography and anterior segment OCT.

A “Cheap” OCT?

Duke University biomedical engineers recently developed a low-cost portable OCT, which produces images comparable to available commercial systems. The device features a 3D-printed spectrometer that costs 1/10th the price of current retail units.

The new type of spectrometer takes the light on a circular path within a 3D-printed plastic, which keeps the optical elements aligned. Misalignments are minimized by the use of a large detector. Estimated cost is $15,000.

New Insight on Retinal Genes

As part of the Human Cell Atlas Project, Australian scientists recently developed the most detailed gene map of the retina. The group looked at over 20,000 individual cells to develop a profile of all major retina cell types and the genes they express for normal function. The group says this understanding is the first step to find out what causes certain retinal diseases and, hence, what treatments to consider. They say more than 200 genes have been associated with retinal disease.

Avastin not Lastin’?

Outlook Therapeutics has completed enrollment in its NORSE 1 Phase III clinical trial of ONS-5010, a proprietary ophthalmic formulation of bevacizumab being investigated as a treatment for wet age-related macular degeneration (wet AMD). The endpoint is mean change in baseline visual acuity at 11 months for ONS-5010 dosed on a monthly basis compared with ranibizumab dosed using the regimen of three monthly doses followed by quarterly dosing. The company claims that ONS-5010 has the potential to mitigate the risks associated with off-label use of Avastin. Its approval may have an impact on the current practice of pharmaceutical compounding of the drug.

Brolucizumab May Hit the Market by the End of 2019

Novartis hopes its recent FDA filing acceptance and priority review of brolucizumab (RTH258) for patients with wet AMD will lead to an end-of-year product launch. Based on the HAWK and HARRIER trials, the anti-VEGF agent is the first and only one to undergo head-to-head trials in patients with wet AMD that prospectively demonstrated efficacy at week 48 starting with a 12-week dosing regimen.




Optic disc melanocytoma, answer A, is a rare, benign lesion that is a variant of melanocytic nevus. Melanocytoma can be confined to the optic disc or extend to the peripapillary choroid and retina. The tumor is black or dark brown in color and can be flat or mildly elevated. While visual acuity is generally unaffected, vision loss can occur due to subretinal fluid, retinal vein occlusion, tumor necrosis or malignant transformation. Though rare, rapid growth and profound vision loss could represent malignant transformation.

B: presumed ocular histoplasmosis (POHS)
C: medulated nerve fiber layer
D: Optic pit



Dr. Raman Bhakhri is an associate professor at the Southern California College of Optometry. He currently teaches the retina and low vision courses at SCCO. He graduated from the University of Alberta with a bachelor of science degree in Biology and received his doctor of optometry degree from the Pennsylvania College of Optometry at Salus University. Dr. Bhakhri completed a post-graduate residency at the Illinois College of Optometry/Chicago Lighthouse in low vision and ocular disease. He is currently a member of the Orange County Optometric Society, California Optometric Association and the American Optometric Association. Dr. Bhakhri is also a fellow of the American Academy of Optometry and currently serves as the vice chair of their Faculty-Student liaison committee. Dr. Bhakhri has authored posters and papers on retina and low vision, and also lectures on those topics at the local, state and national level. Dr. Bhakhri enjoys spending time with his family, playing basketball and travelling.


By Bill Denton, O.D., F.A.A.O.
Chair, Membership Committee

At some point in your career, you realize you just may be coasting. Your knowledge has been limited to the journals you receive and attempt to read, and the conferences that may not be as fulfilling as they once were. You simply need a challenge that will add an extra dimension to your professional learning.

Fellowship in the Optometric Retina Society (ORS) can provide several benefits in addition to the initial challenge of qualifying for this honor. Plenty of perks accompany your induction, but the coolest part is being associated with a body of knowledge and resources which can help you in many other ways. It is not uncommon to receive weekly thought-provoking emails about challenging cases and treatment dilemmas. Some fellows like to share their awesome cases they have diagnosed, while others post their cases with hopes that other Fellows will suggest an alternative differential diagnosis. At times it is like a round-table of brainstorming, but through the use of modern technology. Fellowship has little obligation with a huge opportunity for professional growth.

If you are up to the challenge of becoming a Fellow of the ORS, feel free to peruse the details and application at www.optometricretinasociety.org. Advice can be given to assist you in your quest. Feel free to contact us.



Editor in Chief
Anna K. Bedwell, OD, FAAO

Brad Sutton, OD, FAAO
Journal Reviewers
Larissa Krenk, OD

Jim Williamson, OD, FAAO

Senior Graphic Designer
Matt Egger

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