February 15, 2023

The most important ophthalmology research updates, delivered directly to you.
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In this week's issue

  • Rates of vaccine associated uveitis from COVID-19 vaccines were found to be relatively rare in a retrospective study between 2020-2022.
  • Lower diastolic blood pressure and higher IOP were associated with faster ganglion cell complex thinning in certain glaucoma patients.
  • Despite the benefits of cenegermin therapy, the significant cost warrants further analysis of its cost-effectiveness in patient care.
  • A new study further defines the role of a cyclin-dependent kinase 1 and its upstream regulators in controlling lens fiber cell denucleation. 

The Fab Jab: COVID-19 vaccine associated uveitis


Do COVID-19 vaccinations cause discussions and anterior chambers to flare? A study utilizing data from 40 countries assessed the risk of developing vaccine associated uveitis (VAU) following receipt of a Moderna, Pfizer, or Janssen SARS-CoV2 vaccination between December 2020 and May 2022. The VAU rates per million doses were 0.57, 0.44, and 0.35 for the Pfizer, Moderna, and Janssen vaccines, respectively. Most cases were reported in women (68.56%) and among patients with an average age of 46.24±16.93 years. Additionally, most cases overall were reported after the first vaccination dose (41.32%) and within one week of vaccination (54.02%). Interestingly, the interval between vaccination and VAU diagnosis was significantly longer after vaccination with the Moderna vaccine (21.22±42.74 days) than with Pfizer (11.42±23.16 days) or Janssen (12.69±16.02 days) vaccines (p<0.0001). This study emphasizes the low safety concern for VAU following SARS-CoV-2 vaccination. Further analysis is required to determine immunological or other risk factors in VAU development.

Investigating the relationship between diastolic blood pressure, intraocular pressure, and ganglion cell complex thinning

JAMA Ophthalmology

Tension is growing regarding the role of blood pressure in glaucoma. The relationship between blood pressure (BP) and glaucoma has been a subject of debate. Similar to the concept of cerebral perfusion pressure taught in medical school, ocular perfusion pressure (OPP) is thought to be a potentially important variable dictating the survival of retinal ganglion cells (RGCs). In this model, a steep gradient between capillary pressure and intraocular pressure would result in greater perfusion of RGCs. Assessing the relationship between BP and RGC loss in large-scale studies is complicated by confounding effects including, but not limited to, age, arteriolosclerosis, antihypertensive medications, and intraocular pressure (IOP) lowering treatment. Assessment of OPP alone overlooks the potentially important role of isolated changes in systolic or diastolic BP. A prospective cohort study of 105 eyes from 105 participants between 39 and 80 years of age evaluated the effect of diastolic BP and IOP on macular ganglion cell complex thinning. An analysis using a multivariable model generated from these patients showed that a combination of low IOP and high diastolic BP resulted in the slowest rate of ganglion cell complex thinning, while higher IOP and lower diastolic BP both tended to increase the rate of thinning. These results show an interaction between diastolic BP and IOP that cannot be described by OPP alone, highlighting the need to consider systolic and diastolic BP independently when assessing BP and glaucoma progression. Preventing diastolic hypotension may emerge as a treatment approach for glaucoma, especially for those who are on antihypertensive therapy.

An evaluation of the cost, prescriber, and patient characteristics of cenegermin use in Medicare beneficiaries

American Journal of Ophthalmology

A cost too high to justify? Neurotrophic keratopathy (NK), a degenerative disease of the corneal epithelium, is a challenging condition to manage with limited treatment options. Cenegermin, a recombinant human nerve growth factor eye drop, was approved in August 2018 as the first FDA-approved topical treatment for NK. This retrospective, cross-sectional study analyzed Medicare Part D claims data from 2,410 Medicare beneficiaries who were prescribed cenegermin between January 2019 and December 2020 to evaluate the cost, prescriber, and patient characteristics associated with the use of the drug. The gross cost of cenegermin therapy was $286,907,927 with total out-of-pocket cost for participants equaling $11,993,027 (mean $4951, range [$0 to $32,781]). Prescribers of cenegermin were more likely to be young male (68.2%) ophthalmologists (81.8%) practicing in an urban (90.8%), southern (37.6%) environment. Those prescribed cenegermin were more likely to be white (87.3%) females (63.6%), and compared to overall NK patients, more likely to live in an urban environment. This study highlights the cost-prohibitive nature of cenegermin therapy for NK while also shedding insight into the populations prescribing and taking this medication. Future studies can incorporate data from all patients on cenegermin therapy, determining the cost of the drug to Medicare, and comparing the cost of topical treatment to surgical options.

Canonical cell cycle regulatory molecules are key to clear lenses


What do red blood cells, keratinocytes, and eye lens fiber cells have in common? They all discard their nuclei! A key process in lens fiber cell differentiation is the removal of organelles, resulting in lens clarity.  However, the mechanism for lens fiber cell denucleation (LFCD) is unknown. Prior research has demonstrated a positive association between the clarity of nondividing lens fiber cells and the expression of cell cycle regulatory molecules, such as cyclin-dependent kinase 1 (CDK1). In a chick lens cell culture model of lens development, high CDK1 levels were associated with the timing of LFCD and chemical inhibition significantly delayed LFCD but did not affect lens growth. Similar results were found when the positive regulator of CDK1, CDC25, was inhibited. Furthermore, chemical inhibition of a negative regulator of CDK1,  WEE1,  accelerated LFCD by 60%. PP2A activates WEE1 and inhibits CDC25 and chemically stimulating it resulted in a decrease in LFCD by 40% and inhibiting it increased LFCD by 60%.The necessity of CDK1 for LFCD was further established in experiments with three different mouse models of cataracts which overexpress p27, an inhibitor of CDK1. This study identified key molecules in the LFCD mechanism and highlights other functional roles of these molecules which are classically associated with cell cycle regulation.


Choroidal invasion vs. retinoblastoma survival rates


What histologic features lead to poor outcomes in retinoblastoma? Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. Most RB patients survive beyond 5 years, however, patients with histologic high-risk features (HHRFs) may be predisposed to increased risk of recurrence, metastasis, and death. Choroidal invasion and post-laminar optic nerve involvement (PLONI) are two HHRFs whose significance continues to be debated by experts. This retrospective cohort study aimed to determine the impact of choroidal invasion on survival in patients with retinoblastoma. 393 RB patients diagnosed between 2004 and 2016 were included in the study and divided into no choroidal invasion, focal choroidal invasion, and massive choroidal invasion. Patients with massive choroidal invasion (HR 41.29; 95% CI 4.05-420.49) had significantly higher all-cause mortality when compared to patients with no choroidal invasion; those with focal choroidal invasion (HR 2.69; 95% CI 0.17-43.09) showed no difference in all-cause mortality. Patients with massive choroidal invasion without PLONI demonstrated 5-year overall and cause-specific survival of 100%, whereas patients with massive choroidal invasion and PLONI demonstrated 5-year overall and cause-specific survival of 80.2%. Though limited by the data available in the utilized database, the findings in this study suggest that HHRFs can be predictive of disease course and may help determine appropriate management. 

Lens Landmarks

Nowadays we can’t imagine a world without lasers in glaucoma! Published in 1990, the Glaucoma Laser Trial (GLT) sought to determine the safety and efficacy of Argon Laser Trabeculoplasty (ALT) compared to topical medications (timolol drops) as first-line treatment of primary open-angle glaucoma (POAG). In this multicenter RCT from the early 1990s, 271 patients were included, and the two eyes of each patient were randomized into two groups: ALT first (LF, n = 271) or timolol maleate 5% first (MF, n = 271). 

Key Points:
  • Compared to MF eyes, LF eyes resulted in lower IOP and less reliance on ocular antihypertensive medications at 2-year follow-up
  • Visual acuity and visual fields were stable at 2-year follow-up in both groups
  • A 3.5-year follow-up study found slightly less deterioration in visual fields of LF eyes than in MF eyes
GLT is a landmark study that challenged the traditional paradigm of maximizing medical therapy before utilizing laser treatment. This study found ALT to be effective and safe in patients with POAG and comparable to medical therapy overall. However, despite these findings, ALT was rarely used as a first-line therapy due to the adoption of more effective glaucoma medications (prostaglandin analogues) and due its risk of trabecular meshwork scarring over multiple treatments. ALT paved the way for the introduction of newer forms of laser trabeculoplasty, such as selective laser trabeculoplasty (SLT).

Question of the Week

A 47 year old man presents to the emergency room for new onset blurry vision and a generalized rash. He is sexually active with multiple men and women. He drinks alcohol on the weekends and has smoked 2 ppd since the age of 16. Vital signs are within normal limits. Physical examination significant for the findinging shown below. Ocular examination is significant for chorioretinitis and vitritis.
In addition to testing for syphilis, what is the most appropriate next step in management? 

A. Counsel on smoking cessation
B. Test for HIV
C. Vaccinate the patient for Hepatitis B
D. Start acyclovir

Keep scrolling for answer or click here

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