Optometric Physician

A weekly e-journal by Art Epstein, OD, FAAO


Volume 20, Number 46

Monday, November 2, 2020


Inside this issue: (click heading to view article)
######### Off the Cuff: Talulah

######### Glaucoma As a Prognostic Factor of CRVO: Visual and Anatomical Outcomes and Occurrence of Ischemic CRVO
######### A New Neutrophil Subset Promotes CNS Neuron Survival and Axon Regeneration
  Changes in Metamorphopsia After the Treat-and-extend Regimen of Anti-VEGF Therapy for Macular Edema Associated With BRVO
######### News & Notes

Click on the image for upcoming Conferences and Meetings.


Off the Cuff: Talulah

Although I always have a lot of things to say about optometry, this week I find myself unable. Those of you who are long-time readers or have become friends over the years will understand.

There are few bonds in life as strong as our love of dogs or their love of us. Talulah came into our lives suddenly and unexpectedly when as a little pit bull puppy she rescued herself by jumping into Shannon’s car as she left her office. She was no usual dog. She had a human sense of humor, setting up tricks she would play on me. When she didn’t want to do something, she would let us know by vigorously and dramatically shaking her head NO! She had an incredible personality and never met a person she didn’t like and try to kiss.

Late this past Thursday night, Talulah left us just as suddenly and unexpectedly as she came into our lives. A tumor on her heart, long silent, took her from healthy and playful to desperately ill in just hours, leaving just enough time for Shannon and me to rush her to the emergency vet, and then hold and hug her as she gently passed. We are still in a state of shock and grief. If you have a dog, take a moment to give them a hug and tell them you love them. We so wish we could.

Below is the first editorial I wrote about Lu.

Off the Cuff: The Dog Ate My Passport and Other Misadventures of a Weary Traveler
Two days before I am scheduled to depart on a long and complicated lecture tour across Asia, I leave our new Pit Bull puppy, Talulah (I sometimes refer to her by the humorous nickname Padma Licksmee), sleepily lounging in my office. I scoff down a quick snack and when I return just minutes later, I discover the puppy doing likewise. She looks up at me, oblivious to my rapidly dilating pupils and flaring nostrils, continuing to crunch away on my just (read "cost lots of money") Visa-filled passport. I've never heard anything even remotely like the ear shattering "Nooooooo!" that blares out of my mouth. My vocal cords still ache a week later. Seemingly unconcerned, Talulah just flashes me that mildly confused, "what's all the ruckus about" look that only puppy's have.

Early the next morning, I am on a flight to the National Passport Center in Los Angeles. Twelve hours, hundreds of dollars and more frustration than I would burden you with later, I am back on a (yes, delayed) flight to Phoenix. You should know that the most challenging part was negotiating to get my slightly chewed and (other than the Visas it contained) worthless passport returned. It seems that the feds cannot return damaged passports. They do return undamaged passports but once damaged, your passport goes to the shredder. What is really odd is that once you get your canceled but otherwise undamaged passport back, you are free to damage it. Turned out my passport photo was undamaged and a supervisor generously decided simple cancellation was ok.

Right now, I sit in the airport in Hong Kong en route to Bangkok. I can't get the movie Midnight Express out of my mind. I only hope they believe me when I tell them that the dog ate my passport.


Arthur B. Epstein, OD, FAAO
Chief Medical Editor


Want to share your perspective? Write to Dr. Epstein at artepstein@optometricphysician.com.

The views expressed in this editorial are solely those of the author and do not necessarily represent the opinions of the editorial board, Jobson Medical Information LLC (JMI), or any other entities or individuals.



Glaucoma As a Prognostic Factor of CRVO: Visual and Anatomical Outcomes and Occurrence of Ischemic CRVO

These researchers compared the functional and anatomical outcomes of central retinal vein occlusion (CRVO) according to the presence of glaucoma before the onset of CRVO, and assessed whether pre-existing glaucoma affects the prognosis of CRVO in terms of development and conversion to ischemic CRVO. In this retrospective cohort study, patients with treatment-naïve CRVO were enrolled between December 2009 and February 2019. The patients were classified into two groups according to the presence of pre-existing primary open-angle glaucoma at CRVO diagnosis. Researchers reviewed medical records regarding basic demographics, ocular characteristics and treatments. The effects of pre-existing glaucoma on the occurrence of ischemic CRVO were also investigated using Cox proportional hazard models.

Of 166 eyes from 166 patients, 26 (15.7%) had pre-existing glaucoma. The pre-existing glaucoma group revealed significantly older (69.4 ± 13.3 vs. 56.5 ± 15.9) and lower BCVA at baseline (1.06 ± 0.75 vs. 0.64 ± 0.58, logMAR) and final visits (1.56 ± 1.35 vs. 0.64 ± 0.48, logMAR) than the non-glaucomatous group. In terms of perfusion status of CRVO, the glaucoma group showed higher incidence of ischemic CRVO (30.8% vs. 5.3%) at initial and last visits as well as more disorganization of retinal inner layers (DRIL) at three months (76.0% vs. 49.6%, p=0.015). Pre-existing glaucoma, lower vision at baseline and DRIL at three months were significant risk factors for the occurrence of ischemic CRVO.

In patients with CRVO, pre-existing glaucoma was associated with poorer visual and anatomical outcomes, and played a significant risk factor for the development and conversion to ischemic CRVO with lower vision and presence of DRIL at early phase of CRVO.

SOURCE: Kim YN, Shin JW, Park YJ, et al. Glaucoma as a prognostic factor of central retinal vein occlusion: visual and anatomical outcomes and occurrence of ischaemic central retinal vein occlusion. Acta Ophthalmol. 2020; Oct 28. [Epub ahead of print].


A New Neutrophil Subset Promotes CNS Neuron Survival and Axon Regeneration

Transected axons typically fail to regenerate in the central nervous system (CNS), resulting in chronic neurological disability in individuals with traumatic brain or spinal cord injury, glaucoma and ischemia-reperfusion injury of the eye. Although neuroinflammation is often depicted as detrimental, there is growing evidence that alternatively activated, reparative leukocyte subsets and their products can be deployed to improve neurological outcomes.

In the current study, investigators identified a unique granulocyte subset, with characteristics of an immature neutrophil, that had neuroprotective properties and drove CNS axon regeneration in vivo, in part via secretion of a cocktail of growth factors. This pro-regenerative neutrophil promoted repair in the optic nerve and spinal cord, demonstrating its relevance across CNS compartments and neuronal populations.

Investigators wrote that their findings could ultimately lead to the development of new immunotherapies that reverse CNS damage and restore lost neurological function across a spectrum of diseases.

SOURCE: Sas AR, Carbajal KS, Jerome AD, et al. A new neutrophil subset promotes CNS neuron survival and axon regeneration. Nat Immunol. 2020; Oct 26. [Epub ahead of print].




Changes in Metamorphopsia After the Treat-and-extend Regimen of Anti-VEGF Therapy for Macular Edema Associated With BRVO

This study aimed to investigate the changes in metamorphopsia after administering the treat-and-extend regimen of anti-vascular endothelial growth factor therapy for branch retinal vein occlusion-associated macular edema. Researchers retrospectively examined 27 patients (27 eyes) with macula edema due to branch retinal vein occlusion who received intravitreal injections of anti-vascular endothelial growth factor agents using the treat-and-extend regimen for ≥18 months. They evaluated best-corrected visual acuity, central macular thickness, macular edema recurrence and amount of metamorphopsia, quantified by M-CHARTS.

The best-corrected visual acuity (logarithm of minimum angle of resolution) and central macular thickness significantly improved at 18 months compared with baseline: the median value (interquartile range [IQR]), 0.30 (0.15 to 0.52) and 459 (373 to 542) μm at baseline; and 0 (-0.08 to 0.16) and 267 (232 to 306) μm at 18 months. The M-CHARTS score (the mean of vertical and horizontal scores) significantly decreased at one, six and 12 months compared with baseline, but worsened at 18 month: the median value (IQR), 0.45 (0.250 to 0.925), 0.4 (0.15 to 0.70), 0.4 (0.150 to 0.625), 0.4 (0.225 to 0.550) and 0.45 (0.225 to 0.750) at baseline, one month, six months, 12 months and 18 months, respectively. The median cumulative number of macular edema recurrences was two (IQR, 0.5 to 3.0) at 18 months. Simple linear regression and multivariate analyses revealed that the change in the mean M-CHARTS score at 18 months was significantly correlated with the baseline score and the cumulative number of macular edema recurrences.

Researchers wrote that anti-vascular endothelial growth factor therapy using the treat-and-extend regimen improved metamorphopsia in branch retinal vein occlusion-related macular edema in the short to mid-term follow-up period, but not in the long term. They added that macular edema recurrence may be associated with persistent metamorphopsia.

SOURCE: Mori K, Ishikawa K, Wada I, et al. Changes in metamorphopsia after the treat-and-extend regimen of anti-VEGF therapy for macular edema associated with branch retinal vein occlusion. PLoS One. 2020; Oct 28;15(10):e0241343.


News & Notes

AAOF Announces VSP Practice Excellence Scholarship Recipients
The American Academy of Optometry Foundation and VSP Global announced the recipients of this year’s Practice Excellence Scholarships. Nearly $164,000 was distributed to several top-performing fourth-year optometry students in the US, Puerto Rico and Canada. View the recipients.



Kala Pharmaceuticals Gets FDA Nod for Eysuvis
Kala Pharmaceuticals announced the FDA approved Eysuvis (loteprednol etabonate ophthalmic suspension) 0.25% for the short-term (up to two weeks) treatment of the signs and symptoms of dry-eye disease. Eysuvis utilizes Kala’s Ampplify mucus-penetrating particle drug delivery technology to enhance penetration of loteprednol etabonate into target tissue on the ocular surface. The FDA granted approval to Eysuvis based on results from four clinical trials. Kala Pharmaceuticals plans to launch Eysuvis in the US by year-end. Read more.

  Allergan Announces Positive Topline Results for Investigational Presbyopia Treatment
Allergan, an AbbVie company, announced the Phase III GEMINI I and II clinical trials evaluating the efficacy, safety and tolerability of investigational AGN-190584 (pilocarpine 1.25%) ophthalmic solution for the treatment of symptoms associated with presbyopia, met their primary efficacy endpoints. Additional details will serve as the basis for the FDA New Drug Application submission in the first half of 2021. Read more.

  Orasis Initiates Phase III Studies of Novel Eye Drop Candidate for Presbyopia Treatment
Orasis Pharmaceuticals announced the initiation of NEAR-1 and NEAR-2 Phase III clinical studies evaluating its novel eye drop candidate designed to improve near vision for people with presbyopia. The NEAR-1 and NEAR-2 Phase III studies are multicenter, double-masked, parallel-group clinical trials in the United STates enrolling approximately 600 participants with presbyopia to further evaluate the efficacy and safety of Orasis’ eye drop candidate. Read more.

  Aerie Initiates Phase IIb Trial of AR-15512 for DED Treatment
Aerie Pharmaceuticals announced the start of COMET-1, a Phase IIb clinical trial of AR-15512 (TRPM8 agonist) ophthalmic solution for the treatment of patients with dry-eye disease. The randomized, double-masked, vehicle-controlled trial is evaluating the efficacy and safety of AR-15512 in patients with dry-eye disease. The primary efficacy endpoints are ocular discomfort (symptom) and tear production (sign). Patients will be evaluated on multiple efficacy assessments at days 14, 28 and 84; safety will be assessed at all visits. Topline results from COMET-1 are expected in the third quarter of 2021. Read more.


  FDA Accepts Santen’s NDA for Cyclosporine Topical Ophthalmic Emulsion, 0.1%
Santen announced that the FDA accepted the New Drug Application for cyclosporine topical ophthalmic emulsion, 0.1% for the treatment of severe vernal keratoconjunctivitis in patients ages four to 18. The FDA set June 26, 2021, as the Prescription Drug User Fee Act goal date. The NDA submission for cyclosporine topical ophthalmic emulsion, 0.1% is supported by data from VEKTIS, a 12-month, randomized, multicenter, double-masked, vehicle-controlled, clinical trial. Read more.

  Nicox Selects NO-mediated, IOP-lowering Agent as Development Candidate
Nicox SA selected a new development candidate, NCX 1728, from its proprietary research program focused on nitric oxide-mediated intraocular pressure-lowering agents. An analog of this molecule demonstrated positive results in ocular hypertensive non-human primates compared with travoprost 0.1%, a prostaglandin analog. Further optimization of the ophthalmic formulations of NCX 1728 will continue prior to initiating formal pre-Investigational New Drug tests required for the filing of an IND application. Read more.


  Prevent Blindness Declares November as Diabetes-related Eye Disease Month
Prevent Blindness has declared November as Diabetes-related Eye Disease Month. Educational resources available include downloadable factsheets, training modules, social media graphics and more. Materials are available in English and Spanish. View the new toolkit.





Optometric Physician™ Editorial Board

Chief Medical Editor
Arthur B. Epstein, OD, FAAO

Journal Reviews
Shannon Steinhäuser, OD, FAAO

Contributing Editors
• Katherine M. Mastrota, MS, OD, FAAO
• Barry A. Weissman, OD, PhD, FAAO (Dip CL)

Editorial Board
• William Jones, OD, FAAO
• Alan G. Kabat, OD, FAAO
• Bruce Onofrey, RPh, OD, FAAO
• John Schachet, OD, FIOS
• Joseph Shovlin, OD, FAAO



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