Review of Ophthalmology Online



Vol. 20, #46   •   Monday, November 2, 2020


In this Issue:


Patient-reported Complications Post-intravitreal Injections

Researchers at the the Cleveland Clinic’s Cole Eye Institute note that the majority of IVI-related complications data is derived from randomized controlled clinical trials. Since the nature of these protocol-driven trials limits their applicability to the diverse circumstances seen in routine clinical practice, the researchers say, they undertook a study aimed at determining the prevalence of patient-reported IVI-related complications and their risk factors, in addition to the manner in which patients presented to a tertiary eye care center.

In the retrospective study, the investigators looked at 44,734 injections in 5,318 unique patients seen at the institute between 2012 and 2016. The main outcome measure was a complication(s) within 15 days of injection.

Here were some of the findings:
• Overall, complication rates were low, representing 1.9 percent of all injections, with 1,031 unique complications in 685 (12.9 percent) patients.
• The most common minor complications, or those not requiring intervention, were irritation (n=312) and subconjunctival hemorrhage (n=284).
• The most common serious complications, or those requiring intervention, were corneal abrasion (n=46) and iritis (n=31).
• The majority of complications (66 percent) were adequately managed by a telephone/Epic electronic message encounter only.
• No injection protocol parameter, such as type of anesthesia, preparation or post-injection medication, increased the risk of a complication; however, patient sex, age, number of previous injections and provider strongly influenced the risk of patient-reported complications.

Researchers wrote that, overall, complication rates seen in routine clinical practice were low compared to clinical trial reporting. They added that providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. They suggested that, when performing an IVI, factors such as a patient's sex, age, number of previous injections and provider must be taken into account to ensure the best possible outcomes.

SOURCE: Ramos MS, Xu LT, Singuri S, et al. Patient-reported complications after intravitreal injection and their predictive factors. Ophthalmol Retina 2020; Oct 12. [Epub ahead of print].


Complimentary CME Education Videos


Association of DED Severity with Work Productivity & Activity Impairment

Investigators evaluated the association of dry-eye disease severity with work productivity and activity impairment, as part of a longitudinal, observational study within a randomized clinical trial.

Participants included people with moderate to severe dry-eye disease who enrolled in the multicenter Dry Eye Assessment and Management (DREAM) study.

Participants completed the Work Productivity and Activity Impairment questionnaire at 0, six and 12 months, and were assessed in parallel for symptoms and signs (conjunctival and corneal staining, tear breakup time and the Schirmer test) of DED. Investigators evaluated associations of work productivity and activity impairment with symptoms and signs via linear regression models using generalized estimating equations and controlling for demographics and comorbidities.

Main outcome measures included work productivity (employment, absenteeism, presenteeism [the condition of physically being at work but not functioning properly because of an illness, injury or other condition] and overall work impairment) and activity impairment.

Here were some of the findings:
• Among 535 participants at baseline, 279 (52 percent) were employed, and mean activity impairment was 24.5 percent.
• Among those employed, the mean score was 2 percent for absenteeism, 18 percent for presenteeism and 19.6 percent for overall work impairment.
• Higher Ocular Surface Disease Index symptom scores were associated with greater absenteeism, presenteeism and activity impairment.
• Overall work impairment and activity impairment were greater by 4.3 and 4.8 percent, respectively, per 10 units difference in OSDI score (p<0.001).
• Longitudinal increases (worsening) in OSDI scores were associated with increasing impairment in work (2 percent) and non-work-related activity: (3.1 percent) per 10 units in OSDI (p<0.01).
• Worse corneal staining and tear breakup time were associated with higher overall work impairment and activity level (p≤0.04). However, longitudinal changes in the two signs weren’t associated with changes in work productivity or activity impairment.

Investigators concluded that worse symptoms of DED were associated with decreased work productivity and activity levels, cross-sectionally (inter-individually) and longitudinally within person (intra-individually). They added that corneal staining and tear breakup time were associated with inter-individual differences but not intra-individual changes in work productivity and activity impairment.

SOURCE: Greco G, Pistilli M, Asbell PA, the Dry Eye Assessment and Management (DREAM) Study Research Group. Association of severity of dry eye disease with work productivity and activity impairment in the dry eye assessment & management study. Ophthalmology 2020; Oct 14:S0161-6420(20)31014-9.


Complimentary CME Education Videos


Effect of Mindfulness Meditation on IOP and TM Gene Expression

Scientists evaluated the effect of mindfulness meditation (MM) on intraocular pressure and trabecular meshwork gene expression in individuals with medically uncontrolled primary open-angle glaucoma, as part of a parallel arm, single- masked, randomized controlled trial.

Sixty POAG patients with IOP ≥21 mmHg on maximal topical medication and scheduled for trabeculectomy were included in the study at a tertiary eye-care center in India. Thirty patients (group 1) underwent three weeks of 45 minutes daily MM in addition to medical therapy, while group 2 continued medical therapy only.

The primary outcome was change in IOP (ΔIOP) after three weeks of MM. Secondary outcomes were the probability of success, percentage reduction in IOP, effect on diurnal variation of IOP, change in QOL and changes in gene expression pattern in TM.

Here were some of the findings:
• At three weeks, a significant decrease in IOP was seen in group 1 (20.16 ±3.3 to 15.05 ±2.4 mmHg, p=0.001), compared with group 2 (21.2 ±5.6 to 20 ±5.8 mmHg, p=0.38).
• ΔIOP was significantly higher in group 1 than group 2 (5 ±1.80 vs. 0.20 ±3.03 mmHg, p=0.001).
• Gene expression analysis revealed significant upregulation of nitric oxide synthetase (1 and 3) and neuroprotective genes with downregulation of proinflammatory genes in group 1 compared with group 2 (p=0.001).

Scientists wrote that MM was associated with a significant decrease in IOP and changes in TM gene expression, indicating its direct impact on ocular tissues.

SOURCE: Dada T, Bhai N, Midha N, et al. Effect of mindfulness meditation on intraocular pressure and trabecular meshwork gene expression: A randomised controlled trial. Am J Ophthalmol 2020; Oct 22. [Epub ahead of print].


Lifetime Outcomes of Anti-VEGF Treatment for nAMD

Researchers determined visual acuity outcomes for age-related macular degeneration patients' remaining lifetime, factoring in anti-VEGF treatment. They used multistate modeling with real-world cohort data of 3,192 patients with nAMD (>67,000 visits) treated with anti-VEGF treatment in eye clinics in Australia, New Zealand and Switzerland. Data were analyzed between 2007 and 2015.

Researchers assessed data regarding intravitreal anti-VEGF treatments at the treating physician's discretion and prospective data collection in a standardized registry. The main outcome measure included visual acuity in both eyes over the patient’s remaining lifetime.

Here were some of the findings:
• For the mean remaining lifetime of 11 years, an estimated 12 percent (n=371; CI, 345 to 400) of the sample was expected to retain driving VA, with an estimated 15 percent (n=463; CI, 434 to 495) retaining reading VA in at least one eye.
• An estimated 82 percent of the sample (n=2,629; CI, 2,590 to 2,660) were projected to drop out.
• Younger age at baseline and more injections during the first year of treatment were associated with better long-term outcomes.

Researchers reported that anti-VEGF treatment was associated with preserved useful visual acuity in almost 20 percent of individuals over their average remaining lifetimes. They anticipated that more than 80 percent of patients would cease treatment over that time due to a deterioration of vision beforehand. Researchers added that outcomes without intervention were expected to lead to legal blindness within three years of disease onset in 80 percent of those affected, underlining the necessity of providing anti-VEGF treatment to appropriate patients.

SOURCE: Finger RP, Puth MT, Schmid M, et al. Lifetime outcomes of anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration. JAMA Ophthalmol 2020; Oct 15:e203989. [Epub ahead of print].






Industry News

B+L Introduces SimplifEye IOL Delivery System for Envista Toric & Monofocal Preloaded IOLs

Bausch + Lomb introduced the SimplifEye intraocular lens delivery system exclusively for the enVista MX60PL and the enVista toric MX60PT. The system, which the company says is the first preloaded toric IOL available in the United States, is designed to facilitate smooth and consistent implantation of enVista lenses into the capsular bag in three steps through an incision as small as 2.2 mm. The fully enclosed SnapSet cartridge houses an untouched IOL to help ensure proper positioning and reduce the risk of lens damage, while the beveled tip of the system helps enable consistent lens folding, the company says. Read more.



Kala Gets FDA Nod for Eysuvis

Kala Pharmaceuticals announced the FDA approval of Eysuvis (loteprednol etabonate ophthalmic suspension) 0.25% for the short-term (up to two weeks) treatment of the signs and symptoms of dry eye. Eysuvis uses Kala’s Ampplify mucus-penetrating particle drug delivery technology to enhance penetration of the drug into target tissues on the ocular surface. The FDA granted approval to Eysuvis based on results from four clinical trials. Kala says it plans to launch Eysuvis in the United States by the end of 2020. Read more.



New Norlase Headset Debuts

Norlase recently received 510(k) clearance from the FDA to launch Lion, a green laser photocoagulator that’s fully integrated into a Keeler indirect ophthalmoscope. The company says that, unlike other laser indirect ophthalmoscopes that require a fiber optic connection to a laser source, Lion has no fiber tether, is powered by a battery and uses an advanced wireless interface with optional voice control of laser parameters. Added together, Norlase says that these features result in a lightweight, portable laser treatment solution that can be used in many different settings. Read more.



First Patient Receives Gyroscope’s Investigational Gene Therapy

Gyroscope Therapeutics announced the first patient in its Phase I/II FOCUS trial of its proprietary Orbit Subretinal Delivery System underwent surgery to deliver the company’s investigational gene therapy, GT005, for the treatment of geographic atrophy secondary to dry age-related macular degeneration. Read more.



UCI Study: Restoration of Retinal & Visual Function Post-gene Therapy

In a study at the University of California, Irvine, mice engineered to have inherited retinal disease had their retinal and visual functions restored with a new generation of CRISPR genetic technology. The study, whose findings were published in Nature Biomedical Engineering, applied the new CRISPR approach, called “base editing,” to inherited retinal diseases. Using a Leber’s congenital amaurosis mouse model harboring a clinically relevant pathogenic mutation in the Rpe65 gene, the UCI team successfully demonstrated the therapeutic potential of base editing for the treatment of LCA and potentially other inherited blinding diseases. The treatment also restored retinal and visual function in LCA mice to near-normal levels, the researchers say. Read more.




Nicox Selects NO-mediated, IOP-lowering Agent as Development Candidate

Nicox says it’s selected a new development candidate, NCX 1728, from its proprietary research program focused on nitric oxide-mediated intraocular pressure-lowering agents. The company says an analog of this molecule demonstrated positive results in ocular hypertensive non-human primates compared with travoprost 0.1%, a prostaglandin analog. Read more.



AIVITA’s Stem Cells Found to Help Visual Function in Rats

AIVITA Biomedical announced publication of a study in Investigative Ophthalmology & Visual Science that found retina organoid transplantations with 3D-retina organoids generated from human stem cells demonstrated significant improvement in visual function in RCS rats with retina pigment epithelium dysfunction compared with non-surgery and sham surgery controls. The study was supported by funding from the California Institute for Regenerative Medicine and National Institutes of Health, and led by researchers at AIVITA and the Sue & Bill Gross Stem Cell Research Center of the University of California, Irvine. Read more.



Tarsus Announces IPO

Tarsus Pharmaceuticals announced the closing of its initial public offering of 6,325,000 shares of its common stock at a price to the public of $16.00 per share. All of the shares were offered by Tarsus. The shares began trading on The Nasdaq Global Select Market on October 16, 2020 under the symbol “TARS.” Read more.



Allergan Announces Phase III Topline Results for its Presbyopia Drop

Allergan, an AbbVie company, announced that 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 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. Read more.



Novartis Acquires Vedere Bio, Adding Novel Optogenetic Gene Therapy

Novartis announced it acquired Vedere Bio, adding a new platform for adeno-associated virus (AAV)-based delivery of gene therapies and an optogenetics program for the treatment and prevention of vision loss. The technologies acquired include light-sensing proteins that can be delivered to cells in the retina and unique, AAV delivery vectors that enable treatment via intravitreal injection. 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. Topline results from COMET-1 are expected in the third quarter of 2021. Read more.











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