June 1, 2022

The most important ophthalmology research updates, delivered directly to you.
We're introducing a new Lens initiative called "The Lens Landmarks" where we will be adding a special section summarizing the studies that have most impacted clinical care. Check out this week's summary of the SCUT below and on our website!

In this week's issue

  • Photoreceptor segment thinning identified as an early biomarker for AMD.
  • Residual subretinal fluid after anti-VEGF is associated with better VA, while residual intraretinal fluid is associated with worse VA in neovascular AMD.
  • IOP elevation is common in children and patients using concomitant systemic steroids on topical difluprednate treatment.
  • Transcriptomic profiling of proliferative vitreoretinopathy cells reveals new potential targets for treatments.

Detecting AMD: the utility of photoreceptors instead of OCT photos


Photo(receptors) are worth a thousand words when it comes to early detection of AMD. A recent study of 44,823 patients confirmed photoreceptor layer thinning to be an early biomarker of age-related macular degeneration (AMD). Through logistic regression modeling, retinal layer segmentation, allele identification, genetic and epidemiologic risk factors of AMD were identified. While retinal pigment epithelium (RPE) and Bruch’s membrane (BM) complex thickening occurred after age 57, photoreceptor layer thinning was seen throughout patients’ lifespans. Each standard deviation of such thickening and thinning was associated with increased AMD incidence (p=0.00024). CFH and ARMS2/HTRA1 showed greatest risk for photoreceptor layer thinning, while SYN3/TIMP3 increased risk for BM and RPE thickening. Through identification of such features, we can identify those at risk for AMD earlier than might be apparent on OCT imaging, allowing for more effective intervention.

Visual acuity may be better with residual subretinal fluid in nAMD

JAMA Ophthalmology

A little bit of fluid to help improve visual acuity? Retina specialists commonly encounter cases of neovascular AMD (nAMD) with residual subretinal fluid (SRF) that does not resolve despite repeated anti-VEGF injections. Does the residual SRF actually have an impact on vision? A meta-analysis of randomized controlled trials and observational studies investigated the impact of residual fluid, such as SRF and intraretinal fluid (IRF), on final best corrected visual acuity (BCVA) in eyes treated with anti-VEGF agents for nAMD. In total, 6 randomized controlled trials (RCTs) and 5 observational studies reporting on 3092 eyes were included. The final BCVA of eyes without residual SRF was worse than eyes with residual SRF (weighted mean difference [WMD], 3.1 letter score; 95% CI, 0.05 to 6.18;P= 0.05). During sensitivity analysis, the removal of one observational study resulted in the difference in SRF no longer being significant.  The BCVA of eyes with IRF was worse than those without IRF (P< 0.001). The authors conclude that residual SRF may be favorable to no SRF in eyes treated for nAMD with anti-VEGF injections. The authors acknowledge limitations in the conclusion including baseline differences between comparison groups, the inclusion of observational studies, and a paucity of RCTs. Further RCTs are needed to better elucidate the relationship between SRF and visual acuity.

Who’s at the greatest risk for increased IOP on difluprednate?

American Journal of Ophthalmology

The hottest new steroid treatment may not be for everyone. The mainstay treatment for non-infectious uveitis is topical prednisolone acetate, however difluprednate is a newer synthetic, topical steroid with greater potency and intraocular penetration. As with all topical steroids, there is increased risk for elevated intraocular pressure (IOP) and thus it is important to better understand difluprednate’s effect on IOP. A retrospective, cohort study investigated risk factors associated with clinically important IOP elevation (IOP ≥ 21 mmHg and an increase of ≥ 10 mmHg from baseline) with difluprednate therapy in 54 eyes of 54 patients. Of the 31.5% of patients who developed clinically important IOP elevation, age <18 years and concurrent systemic corticosteroid use were found to be risk factors most associated with elevated IOP during a mean treatment time of 11.3 ± 9.9 weeks. Children treated with difluprednate and those on concomitant systemic corticosteroids respectively had a 7.85 times [95% CI: 1.48-41.56] and 5.31 times [95% CI: 1.18-24.00] greater risk of developing clinically important IOP elevation. While there was no difference in the time to development of clinically important IOP elevation in children, those on systemic steroids met this definition approximately 5 weeks earlier than those without systemic steroid treatment. Despite the limited sample size of children, drug dosing variability, and multiple non-infectious uveitis etiologies, these findings suggest that children and those on concomitant systemic steroids with non-infectious uveitis may not be the best candidates for difluprednate therapy.

Micro meets macro: single-cell profiles identify PVR treatment targets


Business-management guru Henry Mintzberg once said, “Everyone is against micro-managing but macro-managing means you’re working at the big picture, but don’t know the details.” This also applies to clinical medicine. In this study, Laich et al. dove into the details of proliferative vitreoretinopathy (PVR), an ocular scar that forms after damage to the RPE and blood-retinal barrier, often due to retinal detachment or ocular trauma or surgery. Unfortunately, PVRs often cause vision loss necessitating additional surgeries. Therefore, there is a need to identify less invasive pharmacologic prevention or treatment of PVRs. The single cell protein and transcript profiles from 19 PVR tissue samples were compared to the profiles of samples from patients with idiopathic macular pucker (13) or macular hole (12). PVR cells were identified as RPE cells, anti-inflammatory M2 macrophages, or myofibroblasts expressing immune cell markers and found to upregulate thousands of genes, most notably FN1 and SPARC whose proteins are involved in organization of the extracellular matrix. Using the unique transcriptome profile of PVR cells, 13 already-available drugs were identified as potential therapeutic targets, such as aminocaproic acid, known for its ability to halt hemorrhage, and chemo-drugs in the topoisomerase-2A inhibitor class (mitoxantrone, doxorubicin, and etoposide). This study illustrates how single-cell profiling can provide insight into disease processes that help scientists more rapidly identify potential treatment agents.


Corneal endothelial cell loss after endocapsular and supracapsular phacoemulsification


To divide-and-conquer or tilt-and-tumble? That is the question. Phacoemulsification modalities can be subdivided into endocapsular and supracapsular techniques. The endocapsular modalities involve emulsification of the lens within the capsular bag, whereas supracapsular phacoemulsification uses nuclear fragmentation at the iris plane or above. Studies show that supracapsular techniques decrease total procedural time, pain, and energy, but could lead to increased corneal endothelial cell loss (ECL) because the ultrasound is used closer to the endothelial cells. The PERCEPOLIS study aimed to determine whether subluxation supracapsular phacoemulsification was noninferior to the ‘Divide-and-Conquer’ (DaC) endocapsular technique in average central ECL over 1 postoperative year. This was a single center randomized noninferiority trial with 292 total patients. Per-protocol analysis showed that, compared with DaC, subluxation was associated with less ECL relative to baseline at day 4, month 1, and month 3 post op. At 12 months, subluxation was associated with more ECL, within noninferiority limits, however, the study was not sufficiently powered at that point. The subluxation technique was as safe as the DaC method in ECL in the first 3 months post op and provides several benefits that warrant further trials in other centers.

Lens Landmarks

The SCUT trial (2012)

Can you count on corticosteroids to do the scutwork in bacterial keratitis? In the 2012 SCUT study, patients with known bacterial corneal ulcers were randomized to treatment with prednisolone (n = 250) and placebo (n = 250) 48 hours after receiving Vigamox.

Key Points:
  • In the full population, there was no statistical difference in outcomes between the two groups. 
  • For patients with more severe presentation (e.g., CF or worse vision, central ulcers), corticosteroids led to an approximate 2-line improvement.

Overall, the SCUT study is a landmark study because it showed that topical corticosteroids were not dangerous in the treatment of bacterial corneal ulcers and actually led to improved outcomes in a subset of patients with more severe presentations.

See an example of the trial summary page below, though these will only be on the website in the future

Question of the Week

A 32 year-old female presents with a recent history of mood changes, headaches, and ataxia. After undergoing neurological assessment, she was found to have vision loss in the left eye and sensory hearing loss. Brain MRI, fundus image, and subsequent angiogram revealed the following:
What is the most likely diagnosis?

A. Demyelinating disease
B. Systemic lupus erythematosus
C. Ischemic stroke
D. Susac disease

Keep scrolling for answer or click here

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Quiz Answer: D
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