October 13, 2021

The most important ophthalmology research updates, delivered directly to you.
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 The Lens Pod: This week, we are joined by Dr. Jimmy Hu of the New York Eye and Ear Infirmary, who shares with us what medical students should know before their first cornea clinic and OR. Find the episode on Spotify, Apple Podcasts, or our website. Happy listening!

In this week's issue

  • Tebentafusp increased 1-year survival in patients with metastatic uveal melanoma
  • Black, Hispanic, and Medicaid patients were more likely to have more severe diabetic retinopathy upon initiation of anti-VEGF therapy for DME
  • Lifitegrast (brand name Xiidra), an integrin antagonist that prevents T-cell activation and recruitment, had objective and subjective benefits in patients with moderate to severe dry eye disease 
  • Patients with migraines with auras may be at increased risk of retinal artery occlusion

Disparities in Diabetic Retinopathy Severity Upon Treatment Initiation 


Loaded question: How do social determinants of health impact the way communities experience disease and treatment? In a retrospective analysis of 203,707 patients in the IRIS Registry database, investigators sought to identify baseline characteristics associated with worse visual acuity and diabetic retinopathy (DR) severity upon initiation of anti-VEGF therapy for diabetic macular edema. This study found that ethnicity, race, and insurance were all associated with  baseline VA and DR severity. Hispanic patients were more likely to be one level of DR severity higher when compared with non-Hispanic patients (OR 1.71, p<0.01), Black patients were more likely to be one level of DR severity higher when compared with White patients (OR 1.23, p<0.01), and Medicaid patients were more likely to be one level of DR severity higher than Private insurance patients (OR 1.19, p<0.01). These findings illustrate the ophthalmic health disparities that exist in our healthcare system, and the authors highlight the need for future research and public health initiatives to address the underlying barriers that affect DR and DME care.  

Risk of Retinal Artery Occlusion in Patients with Migraines

American Journal of Ophthalmology

In a migraine with aura, there is more than meets the eye. Migraines are known to be associated with photophobia and auras. Yet, the ocular consequences of migraines are not well understood. Researchers sought to determine if an association between migraines and an increased risk of retinal artery occlusion (RAO) existed. With 418.965 migraine patients and matched controls, they employed the cox proportional hazard regression model. 1060 (0.25%) migraine patients were diagnosed with RAO, compared to only 335 (0.08%) of the control patients (HR 3.48). These findings suggest a potential connection between future RAO and a history of frequent migraines. However, could auras make a difference? Patients diagnosed with migraines with aura were at higher risk for incident of RAO (HR 1.58) compared to the patients who had migraines without auras (HR 1.43) (p<0.001). In addition, these patients were found to have several risk factors, most notably acute coronary syndrome, carotid disease, hyperlipidemia, and systemic lupus erythematosus. These results could indicate that migraine patients should be watched more carefully by their ophthalmologist. 

Lifitegrast has Greater Efficacy in More Severe in Dry Eye Disease 

JAMA Ophthalmology

Dry eye disease (DED) is a chronic condition that manifests as burning, grittiness, photophobia, blurred vision, and even pain of the eyes. The pathophysiology of dry eye disease is rooted in tear hyper-osmolarity and ocular surface inflammation, characterized by the infiltration of pro-inflammatory cytokines and subsequent activation of the T-cell response. Previous studies (OPUS-2 and OPUS-3) demonstrated the efficacy of lifitegrast, an integrin antagonist that prevents T-cell activation and recruitment, in DED. This study aims to investigate how patients with different severity of dry eye disease respond to treatment with lifitegrast by performing a post-hoc analysis of patients from the previous two studies, and stratifying them based on the severity of their inferior corneal staining score (CSS) at baseline. They found that patients with an inferior CSS > 1.5 and an Eye Dryness Score of at least 60 at baseline (moderate to severe DED) had a greater chance of achieving clinically meaningful improvement with lifitegrast treatment (1.70 to 2.11-fold odds, p<0.001). This shows that treatment may be more likely to be effective for patients with more severe dry eye. A key feature of this study is that they used both an objective and subjective method of assessing dry eye. Lifitegrast seems to be an effective treatment to target the inflammatory component of DED, particularly in the most affected patients. 

Cataract Surgery Outcomes in Patients with Type 2 Diabetes

British Journal of Ophthalmology

Literature from the 1990s found that visual outcomes in patients with Type 2 Diabetes (T2DM) after cataract surgery were less favorable. However, with developments in cataract surgery, treatment of diabetic retinopathy, and management of diabetes, these findings might change. The authors sought to study cataract surgery in the subdivision of The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study population. In this retrospective case-control study of 1136 eyes of patients with T2DM, 762 eyes (67.1%) achieved a postoperative visual acuity (VA) of 20/40 or better. Factors significantly associated with good postoperative VA were higher level of education (OR=2.35), bilateral cataract surgery (OR=1.55), preoperative VA better than 20/200 (OR=10.59). Notably, diabetes duration, blood pressure, lipid levels and Hemoglobin A1C levels were not significantly associated with better VA outcomes. Per the authors, this is one of the largest studies to assess VA outcomes in T2DM patients after cataract surgery. The authors found that systemic parameters might not be as predictive as ocular measures in assessing postoperative VA.

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Tebentafusp: A breakthrough therapy for metastatic uveal melanoma

New England Journal of Medicine

Tebe or not tebe? Although checkpoint inhibitors are effective treatments for skin melanoma, uveal melanoma has distinctive metastatic patterns and tumor microenvironments. As a result, no standardized treatment has been established for uveal melanoma. Unfortunately, this cancer has a poor prognosis, with 50% of patients developing metastatic disease, which confers a median survival of 1 year.  Tebentafusp is a soluble T-cell receptor and CD3-directed bispecific fusion protein that brings T cells to tumor cells regardless of tumor-antigen specificity or tumor mutational status. Nathal et al. conducted an open-label, phase 3 trial that assigned untreated metastatic uveal melanoma patients to a tebentafusp cohort (N=252) and a control cohort of single agent pembrolizumab, ipilimumab or dacarbazine (N=126). The estimated 1-year survival was 73% in the tebentafusp cohort and 59% in the control (P<0.001). Progression-free survival (or ‘the length of time a patient survives without cancer progression’) at 6 months was 31% and 19% (in the tebentafusp and control, respectively, P=0.01). Although adverse effects were reported in the tebentafusp group (including cytokine-mediated and skin events), they were reduced after the first few doses of treatment. In conclusion, tebentafusp is a unique, novel drug that prolongs survival in patients with untreated metastatic uveal melanoma. This therapy takes a step beyond checkpoint inhibitors, which may be the future for ocular oncology treatment.


Consequences of Intravitreal Injections Delays during the COVID-19 Pandemic 

Ophthalmology Retina

“You miss (the potential for improved vision with) 100% of the (intravitreal) shots you don’t take.” - Wayne Gretzky - Michael Scott - The Lens. Patients with neovascular macular degeneration (nAMD), diabetic macular edema (DME), proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO) typically receive anti-VEGF injections every 4 to 6 weeks to maintain their visual acuity (VA). In a retrospective cohort study, researchers looked at patients with nAMD, DME, PDR, and RVO who required intravitreal injections during the COVID-19 pandemic (March-May 2020) to see if and how their care was disrupted by missed visits. Of the 1041 total patients included in the study, 620 (60%) completed their scheduled visit, whereas 376 (36%) canceled and 45 (4%) no-showed.  The mean change in VA was significantly greater (indicating more vision loss) in patients who canceled (p = 0.0144) and who no-showed (p = 0.0056) on follow-up visit than those who completed their scheduled visit. Patients in the no-show group lost the most vision and had worse baseline vision compared with patients in the completed or canceled groups. Patients with DME, PDR, or both and those with RVO had significantly more vision loss than patients with nAMD. In patients who missed their visit, the average delay in care was 5.34 weeks. In conclusion, no-show patients and those with DME, PDR, or both, and RVO are most vulnerable to vision loss with even short lapses in their care. 

Question of the Week

A 27-year-old woman presents to the office urgently with 4 days of pain, redness, and swelling in her left eye and eyelid. She has no history of trauma or recent illness. The patient is afebrile, however, the skin around the left eye is warm to the touch. Examination of the left eye reveals an IOP of 14, visual acuity of 20/30, and brisk pupillary response. There is no pain with extraocular movements. 
Which of the following is the best treatment for this patient?
A.    Admission to hospital for IV antibiotics
B.    CT scan of orbits with IV contrast
C.    Oral amoxicillin-clavulanic acid
D.    Surgical drainage

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