November 10, 2021

The most important ophthalmology research updates, delivered directly to you.

In this week's issue

There was no significant difference in best corrected visual acuity in a 52-week period for neovascular AMD patients treated with Ranibizumab (brand name Lucentis) versus its biosimilar (SB11)
Hyperosmolar eye drops did not improve early morning corneal edema in Fuchs’ patients
In a study using mendelian randomization, genetically-predicted smoking was associated with advanced and neovascular AMD
Within 5 years of hematopoietic stem cell transplantation, nearly half of patients develop ocular Graft-Versus-Host-Disease

Ranibizumab versus its Biosimilar in Patients with Neovascular Age-Related Macular Degeneration

British Journal of Ophthalmology

Biosimilars are theoretically similar to their brand-name equivalents, but are they the equivalent in practice? Neovascular Age-related Macular Degeneration (nAMD) is a leading cause of blindness and visual impairment across the world, and is associated with $575 million in cost of care. The standard of care has been brand-name anti-VEGF injections. Introduction of biosimilars could reduce cost and improve access to care. The authors sought to study the efficacy and safety of Ranibizumab (RBZ) versus its biosimilar (SB11) over a 52 week period. In this phase III randomized control trial of 705 participants with nAMD, patients were randomized 1:1 to monthly intravitreal injections of 0.5 mg RBZ or SB11. Results showed that there was no significant difference between the change in best-corrected visual acuity (-0.6 letters, 90% CI: -2.1 to 0.9) nor in the adverse event rate (SB11: 31.0%, RBZ 29.7%, p > 0.05). Overall, this study showcases that SB11, a biosimilar of RBZ, and RBZ have comparable efficacy and safety over 52 weeks.

Hyperosmolar Eye Drops Ineffective For Fuchs’

Ophthalmology

Let’s take it back to high school chemistry! The gold standard treatment of Fuchs’ endothelial corneal dystrophy is Descemet membrane endothelial keratoplasty (DMEK), but hyperosmolar eye drops have been posited as a non-surgical option. In this double-masked, randomized control trial of 68 participants, investigators assessed the efficacy of hyperosmolar eye drops on corneal edema resolution in subjects with Fuchs’ dystrophy after early morning eye opening. One eye of each participant was randomized to hyperosmolar eye drop treatment and the fellow eye was randomized to artificial tears placebo. Baseline corneal thickness after eye opening was 626 μm and 622 μm in the treatment and placebo arms, respectively. Hyperosmolar eye drops were not found to have a clinically relevant effect on early morning corneal edema, as the decrease in corneal edema at one hour after eye opening in the treatment and control eyes was not statistically or clinically significant (between-arm difference, 0.7 μm, 95% CI, −2.0 to 3.5; P = 0.59). In addition, eyes treated with hyperosmolar eye drops were more likely to experience adverse effects. These results do not support the routine use of hyperosmolar eye drops for the treatment of corneal edema in eyes with Fuchs’ dystrophy.

Assessing Risk Factors for AMD with Mendelian Randomization

JAMA Ophthalmology

An important application of random assortment in meiosis (hello biology 101) to study risk factors for a leading cause of blindness! Risk factors for age-related macular degeneration (AMD) identified in observational studies include smoking, alcohol consumption, obesity, blood pressure, and metabolic syndrome. Mendelian randomization is a research method that can provide evidence about causal relationships between modifiable risk factors and disease, using genetic variants as natural experiments. In this study, Kuan et al. use mendelian randomization to assess the predicted associations between alcohol intake, smoking initiation, smoking cessation, and lifetime smoking with AMD by a two-sample method, meaning that there were separate data sets used to associate genetic variants with risk factors and genetic variants with AMD status/severity. Genetically-predicted alcohol consumption was associated with geographic atrophy (OR 2.70, p=0.001), but not with advanced or neovascular AMD. Conversely, genetically-predicted smoking initiation was associated with advanced (OR 1.19, p=0.007) and neovascular AMD (OR 1.26, p=0.02). Genetically-predicted smoking cessation was protective against only advanced AMD (OR 0.66, p=0.003). Genetically-predicted lifetime smoking was associated with higher odds of advanced (OR 1.32, p=0.004) and neovascular (OR 1.41, p=0.001) AMD. This study gives further support to the well-documented association between smoking and AMD, and also adds to the less-robust literature implicating alcohol consumption in the disease process. This study is limited by the quality of the genetic evidence supporting the associations with risk factors and the need for cautious interpretation of the effect sizes.

Ocular Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplant

American Journal of Ophthalmology

“I can feel the burn” is something you never want to hear as an Ophthalmologist. GVHD is an autoimmune condition characterized by intense inflammation of a variety of organs following bone marrow/stem cell transplant. Due to the intense regiment these patients undergo, they typically are placed on immunosuppression post-transplant. Ocular signs of GVHD include dry eyes, meibomian gland atrophy, tear loss, and corneal defects. Pellegrini et al. evaluated incidence, risk factors, and complications of ocular GVHD (oGVHD) in patients who underwent hematopoietic stem cell transplantation (HSCT). In this retrospective observational study of 283 patients, the incidence of oGVHD was 19.7% at 1 year, 29.3% at 2 years, 40.7% at 3 years, 47.2% at 4 years, and 49.7% at 5 years after HSCT. This suggests an increase in likelihood for disease the further a patient is from the date of transplant. Additionally, oGVHD was more prevalent with older age (p= 0.020), female sex (p= 0.005), peripheral blood stem cell use (p= 0.004), and previous acute GVHD diagnosis (p= 0.006). Several ocular complications manifested after HSCT, including cataracts, corneal ulcers/perforations, lacrimal obstruction, herpetic keratitis, and CMV retinitis. Within 5 years of HSCT nearly half of the patients developed oGVHD, confirming the importance of routine ophthalmology follow-up.

When is the right time to get my Disability Insurance?

Endophthalmitis after Intravitreal Injections during the COVID19 Pandemic

Retina

The artist Future debated “Mask on” vs.“Mask off” in his billboard hit. Scientists are now largely debating the same in the clinical environment. Oral bacterial flora, specifically Streptococcus, are a concern for endophthalmitis and cause worse visual outcomes than other sources of endophthalmitis. Studies have previously demonstrated that surgical mask use as well as silence by the patient during encounters reduced oral bacterial dispersion onto the surgical field. The COVID19 pandemic provided an opportunity to test the impact of universal mask use on rates of endophthalmitis during intravitreal injection in vivo. This retrospective study looked at 111,679 pre–COVID19 injection encounters (August 2017- March 2020) and 22,418 post–COVID19 intravitreal injection encounters (March 2020- September 2020) in a single center. There was no significant difference found between endophthalmitis rates amongst these two groups, with an incidence of 0.036% pre-COVID19 and 0.031% post-COVID19 (p=0.847). There was also no significant difference between time to presentation between groups or the number of culture positive results. However, ondophthalmitis is a rare occurrence and a longer timeline specifically in the post-COVID19 group may have impacted the significance of these results.

Oncology

106Ru brachytherapy for choroidal melanoma: impacts on macular microvasculature?

BMC Ophthalmology

Can brachytherapy give the vessels a break? Although plaque brachytherapy is a widely used treatment for choroidal melanoma, it frequently causes radiation maculopathy (RM). Optical coherence tomography angiography (OCTA) is emerging as a rapid, non-invasive, and reliable modality to detect these microvasculature changes. Faghihi et al. conducted a retrospective observational case series on unilateral extramacular choroidal melanoma treated with 106Ru brachytherapy. They used OCTA to measure retinal parameters after a mean time of 23.8 ± 15.1 months from treatment. Of 31 patients treated with 106Ru brachytherapy, 25 eyes developed RM, (defined as macular edema, retinal telangiectasia, microaneurysms, cotton wool spots, exudation, hemorrhage, vascular occlusions, capillary nonperfusion, and/or neovascularization). In eyes without RM, irradiation caused reduced vascular area density (VAD) and vascular skeleton density (VSD) in the deep capillary plexus (DCP) (p<0.02), but no difference in the superficial capillary plexus, when compared to non-irradiated eyes. Nine of the RM eyes were ‘burnout’, meaning damage was so severe that vascular structures were not identifiable on OCTA. In conclusion, microvascular effects of 106Ru brachytherapy are more likely to occur in the DCP and OCTA proved a useful modality for evaluating these outcomes.

Question of the Week

A 3 year old boy is brought to the office by his mother after noticing that his left eye has been turning inward for the past few months. Best visual acuity is 20/30 in the right eye and 20/80 in the left eye. Refraction is +1.50 in the right eye, and +4.50 in the left eye. Examination of ocular alignment reveals a left esotropia as shown below.