Current Issue

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In this week’s issue

• Certain systemic medications for T2DM may increase DME risk, while others are protective, suggesting medication choice impacts retinal health.
• Daily low-dose valacyclovir reduces herpes zoster ophthalmicus-related recurrence at 18 months, supporting utility in long-term suppression.
• RVO incidence rose during the COVID-19 pandemic in South Korea among middle-aged adults, while RAO rates remained stable. 
• Nanopore sequencing shows promise for uveitis diagnosis, detecting herpes viruses with up to 75% sensitivity and 100% specificity.
• Phone calls safely replace 1-week post-op strabismus visits with 81% cost savings and better rural access.

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Ophthalmology
Common systemic drugs & DME development in those with T2DM

Turns out some systemic medications do not see eye-to-eye for patients with type 2 diabetes. Type 2 diabetes mellitus (T2DM) remains the leading cause of blindness among adults aged 18 to 64 years in the United States. This retrospective cohort study analyzed over 228,039 patients from the TriNetX database to evaluate how systemic medications impact diabetic macular edema (DME) risk. Patients newly prescribed calcium channel blockers (CCBs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), fenofibrates, or thiazolidinediones (TZDs) were compared to matched controls without these medications after 1-2 years. CCB use was associated with a significantly increased risk of developing DME (hazard ratio [HR] 1.66, 95% CI: 1.54-1.78), while GLP-1 RAs (HR 0.77, 95% CI: 0.70-0.85) and fenofibrates (HR 0.83, 95% CI 0.68-0.98) showed possible protective effects. TZDs showed no significant difference in DME risk. These findings suggest that the choice of systemic medication may affect retinal health and DME development, highlighting potential avenues for new treatments beyond intravitreal injections. Further research is warranted to investigate underlying mechanisms and clinical applications of systemic therapies in diabetic retinal disease.

JAMA Ophthalmology

Can daily valacyclovir keep herpes zoster ophthalmicus at bay?

One pill a day may keep the virus away. Chronic or recurring ocular complications are common in patients with herpes zoster ophthalmicus (HZO), yet evidence guiding long-term antiviral suppression has been lacking. The Zoster Eye Disease Study (ZEDS), a double masked, randomized, placebo-controlled trial across 95 sites from 2017 to 2024, evaluated whether 12 months of treatment with low-dose (1000 mg daily) oral valacyclovir could prevent recurrence of new or worsening eye inflammation (stromal keratitis, endothelial keratitis, dendriform epithelial keratitis, or iritis) in immunocompetent adults with a history of HZO within the last 12 months versus placebo. The study included 527 participants, with 266 in the valacyclovir group and 261 in the placebo group. At 12 months, there was no significant difference in HZO events between the treatment (28%) and placebo (33%) groups (HR= 0.77; adjusted 95% CI, 0.56-1.05). At 18 months, valacyclovir treatment significantly reduced HZO events compared to placebo (32% versus 40%) (HR=0.73; adjusted 95% CI, 0.55-0.97). Overall, suppressive valacyclovir may be a reasonable option for patients with ocular HZO, particularly those experiencing recurrent flare-ups given the benefits observed with extended follow-up.

American Journal of Ophthalmology (AJO)

RAO & RVO during the COVID-19 pandemic: A nationwide analysis

The eyes may be the window to the soul—and to vascular changes observed during the pandemic. COVID-19 has been linked to coagulation dysfunction, which can cause arterial and venous thromboembolic events. Multiple case reports have described retinal vascular occlusion, thrombosis, thrombocytopenia, and myocardial infarction associated with COVID-19 infection, but epidemiological data have not supported an increased incidence of these events at the population level. This study aimed to determine whether the nationwide incidence of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) in South Korea changed between the three years prior to (2017-2019) and after (2020-2022) the COVID-19 pandemic. This was a retrospective population-based cohort study that evaluated data from 326,154 patients with RAO (n=32,028) or RVO (n=304,405), analyzing incidence rate ratios (IRRs) and associations with COVID-19 infection and vaccination across age and sex subgroups. The IRR for RAO was stable across all subgroups. In contrast, RVO incidence increased significantly between 2021 and 2022 among individuals aged 20-39 and 40-64. A significantly greater proportion of RVO patients had underlying comorbidities including hypertension, diabetes, dyslipidemia, thyroid, autoimmune, and chronic liver disease in 2021 and 2022 than in 2019. These findings suggest that metabolic and chronic diseases, not COVID-19 infection or vaccination, underlie the increased RVO incidence during the pandemic in this population.

Investigative Ophthalmology & Visual Science (IOVS)

Nanopore sequencing for uveitis detection

An eye-deal solution for uveitis detection may involve nanopores. Uveitis remains a diagnostic challenge, with infectious causes identified in only 16% of cases despite advanced molecular testing, leaving 37% of cases completely undiagnosed. This study evaluated nanopore metagenomic analysis (NMA), a comprehensive DNA sequencing approach that reads all genetic material present without prior assumptions about which pathogens to look for in 43 uveitis patients using Oxford Nanopore's portable MinION sequencer. Among cases positive for herpes family viruses by standard multiplex PCR (mPCR), NMA successfully detected the viruses in 60% of cases using basic Flongle flow cells, improving to 75% with higher-capacity MinION flow cells, with 100% specificity and no false positives. Cases missed by NMA had significantly lower viral DNA copy numbers, with a median viral load approximately 100-fold higher in detected cases. NMA also detected simultaneous infections with multiple viruses in one patient, demonstrating its hypothesis-free detection capability. This is particularly crucial for herpetic uveitis, which requires prompt antiviral treatment to prevent vision loss. Nanopore sequencing offers a promising advance in diagnosing challenging, vision-threatening uveitis cases with reliable sensitivity and specificity in this study that could improve clinical decision-making.

JAAPOS 

Can you follow up strabismus surgery with just a phone call?

“Can you hear me now?” might be the new gold standard in post-op strabismus care. Strabismus surgery often requires a follow-up visit one week after the procedure (POW1), but in-person visits pose burdens like missed work, school, and distant travel especially for patients in rural or underserved areas. This retrospective study assessed the safety, cost-effectiveness, and accessibility of replacing in-person visits with nurse-led phone calls at POW1 in a cohort of 370 pediatric patients undergoing strabismus surgery at a tertiary referral center. The study compared 188 in-person and 182 phone follow-ups, with complication detection cross-checked at a required in-person visit at postoperative month 3. Phone follow-ups had nearly identical success (96% vs. 95%) and complication detection rates (4.7% vs. 6.1%) as in-person visits, while improving institutional costs by 81% ($14.50 vs. $77.90 per encounter). Importantly, no vision-threatening complications were missed in either group. These results suggest that structured phone follow-ups are a safe, scalable alternative to early post-op clinic visits for strabismus surgery, offering significant cost savings and expanding access for patients who often travel over 50 miles for care.

Ophthalmology Science

Can AI measure proptosis in photos of patients with thyroid eye disease?

What’s in a face? That was the question researchers in Korea asked AI about their patients with thyroid eye disease. Researchers developed a deep-learning neural network to analyze digital facial images, measure exophthalmos, and detect clinically significant exophthalmos changes exceeding 2 mm. They trained the system on 1610 facial images with Hertel exophthalmometry measurements and then validated the system on 511 facial images. When tested with the validation sample, the system achieved a Pearson correlation coefficient of 0.77, an interclass correlation coefficient of 0.73, and an area under the curve of 0.88. The system detected clinically significant exophthalmos change with 74.6% accuracy. These metrics indicate strong reliability and good accuracy of the AI system, indicating that the tool could be used as an alternative to traditional exophthalmometry.

Ocular Hypertension Treatment Study (OHTS)

An ounce of eye drops might be worth a pound of prevention. In the 2002 OHTS trial, subjects with ocular hypertension (but not glaucoma) were randomized to observation or to topical treatment to reduce IOP by 20% and to <24 mmHg. Subjects were monitored for the development of glaucoma.

Key Points

• At 60 months, 4.4% of subjects in the treatment group and 9.5% in the observation group developed POAG (P < 0.0001).
• Treatment reduced IOP in ocular hypertensive subjects from a mean of 25 mmHg to a mean of 19 mmHg while maintaining a favorable safety profile.

Overall, the landmark OHTS trial showed that treating ocular hypertension reduced the risk of developing POAG by more than half. Clinicians should consider treatment in ocular hypertensive patients with moderate to high risk of developing glaucoma.