Current Issue

---

Join The Lens!

Are you interested in being part of The Lens team? Applications are now open and will be due on January 24, 2025 at 11:59 EST. Please click this link to learn more about how you can contribute to The Lens and to apply by the deadline!

In this week’s issue

• Lower systemic blood pressure, measured by 24-hour ambulatory monitoring, is significantly associated with faster visual field progression in glaucoma
• Gene therapy for Bietti crystalline dystrophy using subretinal rAAAV2-hCYP4V2 injections shows potential for improving visual acuity
• Mefunidone, an antifibrotic compound, can prevent the development of posterior capsular opacification in mice

Too busy to read the lens? Listen to our weekly summary on your daily https://creators.spotify.com/pod/show/lens-pod/episodes/The-Lens-Newsletter-January-15--2025-e2tg8av

Ophthalmology

The Link Between Blood Pressure and Glaucoma Progression Rates

When blood pressure dips, does vision slip? Glaucoma, marked by progressive retinal ganglion cell loss, is influenced by factors like IOP and systemic blood pressure. A prospective cohort study examined how 24-hour ambulatory BP monitoring predicts visual field progression. This study enrolled patients with glaucoma or suspected glaucoma in the Vascular Imaging in Glaucoma Study and performed baseline 24-hour ambulatory blood pressure monitoring (ABPM), comprehensive ophthalmologic exams, and follow-up visits every four months to assess systemic blood pressure and rates of visual field progression using standard automated perimetry. Of 124 eyes from 64 participants (mean age 68.4 years), lower systemic arterial pressure measured by 24-hour ABPM was associated with faster visual field (VF) progression; specifically, each 10-mmHg decrease in average 24-hour MAP, daytime MAP, and 24-hour SBP was associated with faster MD loss rates of –0.171 dB/year (P = 0.045), –0.229 dB/year (P = 0.003), and –0.137 dB/year (P = 0.023), respectively. Similarly, lower office-based mean SBP was correlated with faster progression (–0.158 dB/year per 10-mmHg decrease, P = 0.003). This study highlights that lower baseline 24-hour mean arterial pressure (MAP) and systolic blood pressure (SBP), as well as low SBP during follow-up, are significantly associated with faster rates of glaucomatous visual field progression. This suggests that 24-hour ambulatory blood pressure monitoring could be a valuable tool for assessing progression risk, particularly in patients with low intraocular pressure, while emphasizing the need for further research on the therapeutic role of systemic blood pressure management in glaucoma care.

JAMA Ophthalmology

Outcomes following gene therapy for Bietti crystalline dystrophy

Your eyes, a universe? Effective treatment for Bietti crystalline dystrophy (BCD), a severe genetic retinopathy due to variants in the CYP4V2 gene, has yet to be discovered in recent years. In a nonrandomized clinical trial, 12 patients with genetically confirmed BCD received subretinal injections of rAAAV2-hCYP4V2 at 1 of 2 dosage levels and were followed up for 12 months. Primary endpoint was clinical evidence of ocular inflammation by evaluation of clinical chemistry and immunogenicity testing. Secondary endpoints were changes in visual function from baseline in best-corrected visual acuity (BCVA), microperimetry and contrast sensitivity 12 months after treatment. At 12 months, the study eye improved by a mean (SD) letter score of 13.9 (13.1) compared with 6.3 (7.4) in the non-study eye. The 12-month median (IQR) BCVA for the study eye was 53 (37-64) and 62 (42-70) for the non-study eye. To conclude, gene therapy in patients with BCD may produce mild improvement in BCVA although additional research is needed to remove confounding variables. 

IOVS

Novel anti-fibrotic compound could prevent PCO development

Uh oh another PCO… Posterior capsular opacification (PCO) is a common complication of cataract surgery, affecting 20-50% of patients within 5 years. Post-surgical inflammation causes lens epithelial cells (LECs) to undergo epithelial to mesenchymal transition (EMT), resulting in migration and abnormal differentiation of cells and subsequent visual obscuration. It is treated with a YAG laser capsulotomy. Mefunidone (MFD), an anti-fibrotic compound previously studied in diabetic nephropathy and pulmonary fibrosis, has been identified as a potential tool to prevent PCO development. Researchers tested MFD in two mice models, one group treated with TGF-β to induce EMT, and the other group treated with H2O2 to induce oxidative stress and inflammation. Following extracapsular lens extraction (ECLE), the mice received injected intracameral MFD. Expression levels of multiple EMT markers (α-SMA) and inflammatory markers were measured. In the EMT model, MFD showed a concentration-dependent decrease in a-SMA in lens epithelial cells, a marker of EMT, and decreased PCO severity. In the oxidative stress model, MFD attenuated the levels of malondialdehyde in the capsular bag, a measure of oxidative stress. MFD also delayed the decline of glutathione levels, a potent antioxidant. This study demonstrated the ability of MFD to suppress inflammation and EMT, crucial elements of PCO development. Further investigation is required to see if this decrease in PCO severity is clinically significant enough to recommend MFD as a novel PCO prevention method. 

JAAPOS

Risk factors for ROP in privately insured babies with low gestational age and birth weight Weighting for the signs: Retinopathy of Prematurity (ROP) is one of the leading causes of blindness in the United States. It consists of uncontrolled vascular development and affects premature infants. Primary risk factors for ROP are young gestational age (GA) and low birth weight (BW). Current screening guidelines include: BW < 1500 g, GA < 30 weeks, or BW 1500-2000 g or GA > 30 weeks with an unstable post-delivery period. This retrospective cohort study aimed to understand how neonatal comorbidities can lead to severe ROP (sROP) in infants with severe comorbidities that may otherwise be considered low risk. 8789 infants were identified to have ROP and placed in groups A (BW < 1000 g and GA < 29 weeks) or B (BW >1000 g and GA > 29 weeks). 425 (4.8%) developed sROP, requiring a procedure. Group A consisted of 2726, 387 (14.2) needing a procedure; Group B consisted of 6063 patients, 38 (0.6%) needing a procedure. In Group A, intraventricular hemorrhage and patent ductus arteriosus ligation were the comorbidities that increased the risk sROP. In Group B, infection was the risk factor that increased sROP. Poor postnatal weight gain was also found to be a risk factor for ROP development; possibly due to metabolic derangements, such as low IGF-1, or inflammation. This study supports the claim in a related study that “all children with severe medical issues should be screened for ROP.”

Journal of Cataract and Refractive Surgery

Artificial intelligence-driven lens calculation

AI has an eye for lens calculation, even for short-sighted eyes! Accurate intraocular lens (IOL) power calculation is critical for optimizing refractive outcomes after cataract surgery. The Barrett Universal II (BUII) and Kane formulas are considered gold standard methods for IOL power prediction. The BUII formula incorporates effective lens position, axial length, keratometry, anterior chamber depth, and lens thickness to provide reliable refractive outcomes. On the other hand, the Kane formula factors axial length, keratometry, anterior chamber depth, and social demographics to enhance accuracy of power calculations. Both formulas excel in refractive prediction and produce consistent high-quality results. This retrospective case series evaluated the ZEISS AI IOL calculator, an AI-based IOL formula, and compared its predictive accuracy to the BUII and Kane formulas using data from 10,838 eyes. Results showed that ZEISS AI outperformed both BUII and Kane formulas with significantly lower prediction error and a higher percentage of eyes achieving refractive outcomes within ±0.50 D of what was predicted, especially in myopic eyes. In the entire dataset, ZEISS AI demonstrated greater accuracy, highlighting its potential for improved IOL power calculation, especially for challenging cases involving myopic eyes.

POINT Trial for Uveitic Macular Edema

Treating uveitic macular edema? This study will POINT you in the right direction. Before the POINT trial, commonly used therapeutics for uveitic macular edema had not been directly compared, with literature supporting the efficacy of each. In the 2019 multicenter POINT clinical trial, the efficacy of periocular triamcinolone acetonide (PTA, n=73), intravitreal triamcinolone (ITA, n=79) and intravitreal dexamethasone implant (IDI, n=78) for treatment of uveitic macular edema were compared. 

Key Points:

• ITA and IDI groups had BCVA improvement 5 letters greater than the PTA group at 8 weeks (p<0.004)
• IDI and ITA were superior to PTA in improving and/or resolving uveitic macular edema
• Risk of IOP ≥ 24 mmHg was higher in the intravitreal groups compared to the periocular group: hazard ratio (HR) 1.83 for ITA, 2.52 for IDI

Overall, the POINT trial found intravitreal corticosteroid treatments (ITA and IDI) to be better therapeutic agents than periocular corticosteroids (PTA) for uveitic macular edema. However, rates of increased IOP were greater in the ITA and IDA groups.