FROM THE DESK OF THE EDITOR

Greetings. A busy summer has now transitioned into a busy fall around my office and household. I always find myself saying the next month will be less crazy and chaotic. It never is as I always end up signing up for more. My kids are now older and busier with activities, adding another layer to our balancing act. In my younger pre-children era, I found the idea of traveling for work to be glamorous and exotic. The allure to travel has certainly shifted in my mindset over the years. I have thought about this much more recently as I have been making plans for the upcoming Academy meeting in November. The meeting is scheduled in my home base, Indianapolis. For this meeting, I won’t have to travel at all! I am glad to avoid the plane travel, as that seems to be the biggest headache with worries of delays, making layovers, and cancellations. But on the flipside, I really enjoy a few nights of sleep in a hotel room all to myself, checking out local restaurants and exploring a new city. However, it will be a nice change of pace to be in the host city and show friends what I like about Indianapolis.

My husband, also an OD but in a private office setting, prefers to avoid travel and stay local or online for as much continuing education as possible. He does not share my extrovert personality trait. He is not as keen on attending large CE meetings. Fortunately, optometric continuing education offers various platforms and settings to suit all needs from online (self-study or interactive) to local, state and national CE meetings. What is your preference travel—local, small vs. large meeting? Now, insert shameless Optometric Retina Society plug…If you like a mid-size meeting with engaging speakers focused on all things retina, check out Retina Update 2024. The meeting is scheduled December 7-8, in Carlsbad, CA. Wherever your preference lies, at least for now, enjoy the retina focused content below.

YOU MAKE THE DIAGNOSIS

A 42-year-old Caucasian, female was referred for evaluation of left optic nerve swelling and acute vision change

Click here for case and answer.

IMAGE GALLERY

Which of the following images represents central areolar choroidal dystrophy?

Answer appears later in newsletter.

JOURNAL ABSTRACTS

Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes

Retinal toxicity is a well-known and potentially serious complication of long-term hydroxychloroquine (Plaquenil) use. Established factors that convey increased risk of retinal damage include concurrent Tamoxifen use, daily dosing above 5.0 mg/kg/day, increased duration of use/cumulative dose, kidney disease, and other pre-existing maculopathy. This large, retrospective study may well have added two more risk factors to the list. A record review performed at the Kaiser Permanente Northern California Integrated Health System encompassed 4677 patients taking hydroxychloroquine for a duration between 5 and 15 years and undergoing regular ocular screening. Overall, 125 of these patients developed retinal toxicity (102 parafoveal and 23 perifoveal). In addition to reinforcing previously known risk factors, two more risk factors were identified. Females had a four times greater risk of developing retinal toxicity than did males. In addition, older age at the initiation of treatment was found to be a significant risk as well. For example, compared to starting treatment before age 45, patients who started treatment between 45 and 55 had a 3X increased risk, those starting between 55 and 65 were at 4X greater risk, and starting after age 65 carried a 6X greater risk. Another interesting finding related to pericentral damage vs. parafoveal damage. It has been established that Asian patients tend to experience pericentral damage as opposed to paracentral damage. That was confirmed in this study, with the rate of pericentral damage in Asians being 15 times higher than the rate of pericentral damage in Caucasians. However, an increased rate of pericentral damage was also seen in this study in African American patients, with a rate 5 times greater than Caucasians. However, there were only five African Americans in the study who developed retinal toxicity. Even though three of the five had pericentral damage and two had paracentral damage, the small number of patients in this category necessitates confirmation of this finding with future studies.

Jorge AM, Melles RB, Marmor MF, et al. Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes. JAMA Netw Open. 2024 May 1;7(5):e2410677.

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Survival in Uveal Melanoma Patients is Linked to Genetic Variation at HERC2 SNP rs12913832

Uveal melanoma is associated with fair skinned individuals with light-colored eyes. This study examined the relationship between eye color and uveal melanoma (UM) prognosis. This retrospective study used the single nucleotide polymorphisms (SNPs) that have been linked to eye color using the IrisPlex system, which calculates the probability of blue, intermediate and brown eye color. DNA was sequenced from 392 patients with UM undergoing enucleation at the Leiden University Medical Center in The Netherlands. Using IrisPlex, 307 (78%) were predicted to have blue eyes, 74 (19%) brown eyes, and 11 (3%) could not be inferred.

The authors found those with G/G genotype, linked to blue eyes, of rs12913832 (HERC2) had a shorter survival (p= 0.04) over individuals with an A/G or A/A genotype, associated with non-blue eye color. The authors then analyzed parameters that could result in this difference of survival, looking at tumor and patient characteristics. The G/G genotype group had a higher proportion of tumors (p=0.04) with monosomy of chromosome 3, a somatic genetic aberration associated with higher risk of developing metastases. They concluded that the G/G genotype of HERC2, associated with blue eye color, not only carries a higher risk for UM development but also an overall worse prognosis over other genotypes.

Gelmi MC, Houtzagers LE, Wierenga APA, et al. Survival in uveal melanoma patients is linked to genetic variation at HERC2 SNP rs12913832. Ophthalmology. 2024 Sep 6:S0161-6420(24)00540-2. doi: 10.1016/j.ophtha.2024.09.001. Epub ahead of print.

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Risk of Stroke, Myocardial Infarction, Deep Vein Thrombosis, Pulmonary Embolism, and Death after Retinal Vein Occlusion

Patients with cardiovascular disease are at higher risk than the general population for developing retinal vein occlusions. This retrospective study set out to determine if patients experiencing retinal vein occlusion (RVO) were then in turn at higher risk for serious systemic complications compared to matched patients with similar cardiovascular disease. A combined electronic health record research database, TriNetX, representing clinics in four countries including the United States, was utilized. Retinal vein occlusion patients were assessed for stroke, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), and death at the one year, five year, and ten year marks after diagnosis. The RVO patients were matched to a group of patients who had been diagnosed with cataracts, and were matched based on age, sex, ethnicity, race, and relevant systemic comorbidities (hypertension, diabetes, hyperlipidemia). Both groups excluded patients who had already experienced a stroke, MI, DVT, or PE in the two years prior to diagnosis. A very impressive total of 45,303 patients were included in both the RVO group and the control group. Compared to the matched controls, RVO patients were at a significantly higher risk of death at 1, 5 and 10 years. They were also at significantly greater risk of stroke and PE at all time points, and of MI at 1 and 5 years. In addition, RVO patients were at significantly greater risk of DVT at 1 year with equal risk at 5 and 10 years. Interestingly, further analysis revealed that central retinal vein occlusion patients were at greater risk of death at all time points than were branch vein occlusion patients.

Wai KM, Ludwig CA, Koo E, et al. Risk of Stroke, Myocardial Infarction, Deep Vein Thrombosis, Pulmonary Embolism, and Death After Retinal Vein Occlusion. Am J Ophthalmol. 2024 Jan;257:129-136.

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Emerging Role of Vitamin D Deficiency as a Risk Factor for Retinal Venous Occlusions and Need for Public Health Measures for its Prevention

Multiple studies have shown a positive correlation between vitamin D deficiency and vascular diseases. Vitamin D supplementation has also been found in research studies to improve vascular endothelial function. This study included 54 age-and sex-matched cases of RVO (retinal vein occlusion). Serum vitamin D levels were measured in RVO patients and the control group and both groups were found to be low: 14.19 +/-5.23ng/ml and 19.42 +/-10.27ng/ml respectively. The odds ratio of 10.558 indicates vitamin D deficiency to be strongly correlated with RVO. The authors conclude that a serum vitamin D level should be part of a routine investigation after CRVO, and deficient patients should be counseled on the importance of sunlight exposure as well as oral supplementation of vitamin D.

Sahu PK, Gautam P, Das GK, et al. Emerging role of vitamin D deficiency as a risk factor for retinal venous occlusions and need for public health measures for its prevention. J Family Med Prim Care. 2024 Aug;13(8):3298-3303.

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Central Retinal Artery Occlusion: A Retrospective Study of Disease Presentation, Treatment, and Outcomes

This retrospective study was designed to assess the presentation, treatment, and outcomes of CRAO (central retinal arterial occlusion) at a tertiary care center in Canada over 2 years. Twenty-seven patients were included in the study and the majority of CRAO patients (63%) presented initially to eye care providers or primary care physicians. Eighty-nine percent of patients presented more than 4.5 hours after symptom onset, which is considered outside the window to receive thrombolytic treatment. Despite a growing body of evidence and ongoing clinical trials evaluating the use of intravenous thrombolytic therapy for CRAO, few patients present within the window for treatment, and institutional protocols do not exist. Also of note, 75% of neurologists surveyed believed that acute CRAO requires urgent referral to a stroke center, only 18% of retina specialists agreed. The authors conclude the need for greater public health strategies to enhance awareness that acute monocular vision loss is a medical emergency that should be evaluated immediately at the nearest stroke treatment center. Ocular maneuvers (e.g. ocular massage, anterior chamber paracentesis, or topical intraocular pressure lowering medications) may be offered acutely at primary eye care providers’ offices. However, vascular imaging, thrombolytic therapy, and stroke risk factor modification may be delayed beyond the therapeutic window of opportunity.

Smith MJ, Benson MD, Tennant M, Jivraj I. Central retinal artery occlusion: a retrospective study of disease presentation, treatment, and outcomes. Can J Ophthalmol. 2023 Aug;58(4):318-323.

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Association between Pentosan Polysulfate and Subsequent Maculopathy: Insights from a Nationwide Population-Based Study in Korea

Reported initially in 2018, pentosan polysufate (PPS), a semisynthetic sulfated polysaccharide used in the treatment of interstitial cystitis, has been linked to development of pigmentary maculopathy. This retrospective cohort study further evaluated that causation using the South Korean social health insurance system, which mandates nationwide enrollment. Patients were identified using the cystitis diagnostic code (n=309,345). From there, it was screened for prescription of PPS (n=103,553) and diagnosis of a broad range of maculopathy diagnosis codes. Both groups either taking or not taking PPS had similar rates of seeking eye examinations.

This study confirmed in univariate and multivariate analyses a significant association between taking PPS and subsequent development of maculopathy. Of note, the study found a much high proportion of male PPS users (41.6%) in Korea for a drug that elsewhere is mostly prescribed to females. This study provides more insight into risk for PPS maculopathy for Asian individuals and provides further evidence of causation.

Kwon HY, Kim J, Ahn SJ. Screening practices and risk assessment for maculopathy in pentosan polysulfate users across different exposure levels. Sci Rep. 2024 May 17;14(1):11270.

IN THE NEWS

Genentech to Reintroduce Susvimo Implant

Genentech reports plans to have Susvimo (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant available again soon to US retinal specialists. In October 2022, Genentech voluntarily recalled the implant (insertion tool and fill kit) after determining the implants were not performing to standards. At present, Genentech has updated the implant and refill needle reporting that they now meet performance standards. The FDA has authorized a post-approval supplement to the Biologics License Application for Susvimo.

Susvimo utilizes a Port Delivery Platform to deliver ranibizumab for eyes with exudative AMD. After a one-time surgical implantation of the device, a specially designed fill needle kit is used to refill the implant every 6 months.

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CPT Code Approved for Photobiomodulation Therapy in Retinal Disease

A new Category III CPT code, XX69T, for single session of photobiomodulation therapy has been approved by the American Medical Associations CPT Editorial Panel. The code will take effect on January 1, 2025, to claim reimbursement for photobiomodulation therapy of the retina for patients with non-exudative AMD. The approval was based on positive data from the LIGHTSITE III trial which demonstrated improvement in BCVA using LumiThera’s Valeda photobiomodulation device on eyes with early or intermediate AMD. The Valeda device is available in Europe and Latin American countries. LumiThera has submitted a De Novo request to the US FDA for reclassification of Valeda to a Class II device for treatment of non-exudative AMD.

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FDA Approves Sandoz’s Enzeevu (Eylea Biosimilar)

Sandoz, a leader in generic and biosimilar medicine, announced the US FDA has approved Enzeevu (aflibercept-abzv) for the treatment of exudative AMD. The FDA deemed Enzeevu would be interchangeable with the reference medicine, Eylea (aflibercept), supported by data from the Mylight study. The launch date of Enzeevu has yet to be determined. Earlier in 2024, the company announced acquisition of a ranibizumab biosimilar, Cimerli (ranibizumab-eqrn) from Coherus, further strengthening their ophthalmological platform.

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Heidelberg Faster OCTA Cleared by FDA

FDA has granted clearance to Heidelberg Engineering’s Spectralis OCTA Module with Shift technology. The device produces high-resolution OCTA images with a lateral resolution of 5.7 microns/pix at a scan speed of 125 kHz, decreasing scan acquisition time by 50%. The 125 kHz scan speed enhances visualization of fine capillaries while limiting artifacts.

IMAGE QUIZ ANSWER

Image C correctly identifies central areolar choroidal dystrophy (CACD), an inherited macular dystrophy. CACD develops in an autosomal dominant inheritance pattern as a result of variants in the PRPH2 gene. Macular pigmentary changes develop between the 3rd and 5th decade and gradually progress into a bilateral well-defined atrophic lesions, as demonstrated in the image here. Severe vision loss typically develops given the extent of atrophy in the macula. The clinical appearance can look similar to geographic atrophy AMD particularly confounding when late-onset CACD occurs. Genetic testing and family history can help to differentiate. There is no treatment for CACD, gene therapy is under investigation.

A: Best’s dystrophy (CNV stage)
B: Choroideremia
D: Doyne’s dystrophy

MEET THE FELLOWS

Dr. Kensington Hatcher is a 2013 graduate of the Illinois College of Optometry. He recently joined Neurotech as a senior medical science liaison, after nearly 3 years on the medical affairs team at Apellis. Prior to joining Apellis in 2021, he was in clinical practice for 8 years, the last 5 of which were at Virginia Eye Institute, a large multidisciplinary ophthalmology practice. He is a Fellow of the American Academy of Optometry and currently serves on the Admittance Committee. His research interests include ophthalmic imaging biomarkers for retinal disease. He and his family live in Chicago.

WHY BECOME AN ORS FELLOW?

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.