PURPOSE: This study evaluated the structural and functional alterations of corneal nerves in unilateral noninfectious anterior uveitis patients. DESIGN: Cross-sectional study. METHODS: Eighty-two patients with unilateral...PURPOSE: This study evaluated the structural and functional alterations of corneal nerves in unilateral noninfectious anterior uveitis patients. DESIGN: Cross-sectional study. METHODS: Eighty-two patients with unilateral noninfectious anterior uveitis were included. Affected eyes were assigned to the affected group, contralateral clinically unaffected eyes to the unaffected group, and eyes from 25 healthy subjects to the control group. Corneal sensitivity was assessed using non-contact corneal aesthesiometer (NCCA), followed by Cochet-Bonnet aesthesiometer (CBA). Corneal subbasal nerve plexus was imaged using in vivo confocal microscopy, and nerve morphology parameters were quantified using ACCMetrics software. A masked observer assessed central corneal inflammatory cell density and microneuroma counts. Based on anterior chamber cell grade and treatment status, patients were further stratified into subgroups for exploratory analyses. RESULTS: NCCA thresholds were significantly higher in affected eyes than in controls (β = 0.97; 95% CI, 0.63 to 1.31) and in unaffected eyes (β = 0.48; 95% CI, 0.23 to 0.72; all adjusted p < 0.001). Moreover, compared with controls, affected eyes exhibited significantly lower corneal nerve parameters, notably CNFL (β = -6.09; 95% CI, -7.44 to -4.74), alongside higher inflammatory cell density and microneuroma counts (all adjusted p < 0.001). Relative to controls, unaffected eyes also demonstrated measurable differences, including higher NCCA thresholds, reduced CNFL, CNFD, and CFracDim, as well as increased microneuroma counts (all adjusted p < 0.010). CONCLUSIONS: Unilateral noninfectious anterior uveitis was associated with reduced corneal nerve sensitivity and altered nerve parameters in the affected eye, and measurable differences in the contralateral eye.
PURPOSE: To determine the association between menopausal hormone therapy (MHT) and strabismus outcomes in menopausal women. DESIGN: Retrospective clinical cohort study. PARTICIPANTS: Female patients whose first menopausa...PURPOSE: To determine the association between menopausal hormone therapy (MHT) and strabismus outcomes in menopausal women. DESIGN: Retrospective clinical cohort study. PARTICIPANTS: Female patients whose first menopausal diagnosis occurred between ages 44 - 60 years old in the Epic Cosmos database were included from January 1, 2010 to October 31, 2025. MHT exposure was defined as estrogen or combined estrogen-progestin products for ≥90 days after menopause diagnosis. Patients who used MHT before a diagnosis of menopause were excluded. The control group included menopausal patients who were not prescribed MHT. METHODS: Demographic, clinical history, and MHT characteristics were extracted for patients. The association between MHT and strabismus outcomes was evaluated using time-varying Cox proportional hazards models. Covariates included age at menopause diagnosis, year of menopause diagnosis, race, and ethnicity. MAIN OUTCOME MEASURES: The primary outcomes were strabismus diagnosis, strabismus surgery, and reoperation. Patients who had congenital, mechanical, neurological, paralytic, traumatic causes of strabismus were excluded. RESULTS: 2,154,255 menopausal patients were included (age of menopause: 54.9 (4.1) years and 67.3% identified as White). Of these patients, there were 197,576 (9.2%) in the MHT cohort and 1,956,679 (90.8%) in the non-MHT cohort. In time-varying Cox models, MHT use was associated with a higher hazard of strabismus diagnosis (HR 1.11, 95% CI 1.02 to 1.22, P=0.015) and surgery (HR 1.76, 95% CI 1.38 to 2.25, P<0.001), while no significant association was observed for reoperation. CONCLUSION: MHT was associated with a higher hazard of strabismus diagnosis and strabismus surgery in menopausal females. These findings offer new insight into the potential influence of MHT on ocular alignment and visual outcomes.
Kim TY, Choi EY, Lee S
… +5 more, Choi YJ, Park SI, Lee SM, Lee J, Kim M
Am J Ophthalmol
· 2026 Jun · PMID 42379333
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PURPOSE: To evaluate the clinical performance of ultra-widefield swept-source optical coherence tomography (UWF-OCT) in the assessment of choroidal tumors and to compare it with ultrasonography (US), spectral-domain (SD)...PURPOSE: To evaluate the clinical performance of ultra-widefield swept-source optical coherence tomography (UWF-OCT) in the assessment of choroidal tumors and to compare it with ultrasonography (US), spectral-domain (SD)-OCT, and magnetic resonance imaging (MRI). DESIGN: Retrospective diagnostic comparison. SUBJECTS: Thirty-nine eyes from 39 patients diagnosed with choroidal tumors at a single tertiary referral center. METHODS: This retrospective diagnostic comparison evaluated patients diagnosed with choroidal tumors at a single tertiary referral center between January 2023 and August 2025. All patients underwent UWF-OCT imaging at diagnosis. Tumor measurements obtained with UWF-OCT were compared with US, SD-OCT, and MRI. Comparative analysis among imaging modalities and predictors affecting UWF-OCT applicability was performed. MAIN OUTCOME MEASURES: Tumor thickness (mm) and largest basal diameter (LBD, mm) measurements, and complete measurability rate across different tumor size categories. RESULTS: Thirty-nine eyes from 39 patients (mean age 59.2±16.9 years) were analyzed, including 27 choroidal melanomas (69.2%), 5 metastatic tumors (12.8%), 4 hemangiomas (10.3%), 2 osteomas (5.1%), and 1 (2.6%) indeterminate choroidal melanocytic lesion. UWF-OCT successfully measured both tumor thickness and largest basal diameter (LBD) in 100% (31/31) of small and medium choroidal tumors, substantially outperforming SD-OCT (complete measurement achieved in 63.6% of small tumors, and 0% of medium or large tumors). UWF-OCT measurements were systematically smaller than ultrasonography (thickness: -32.3%, P<0.01; LBD: -11.1%, P<0.01) and MRI (thickness: -29.2%, P<0.01). Mushroom-shaped tumor morphology was the strongest negative predictor of UWF-OCT quality (OR=0.015, 95% CI 0.001-0.196, P<0.01). UWF-OCT's complete measurability was limited in large tumors (12.5%, 1/8). CONCLUSIONS: UWF-OCT provides precise, noninvasive, single-scan assessment of small-to-medium choroidal tumors with detailed structural visualization. It may be particularly useful for dome-shaped tumors, while multimodal imaging with US and MRI remains optimal for complex morphologies. Overall, UWF-OCT represents a valuable tool for diagnosis and treatment planning, with potential utility for longitudinal follow-up in choroidal tumor management.
Rajak SK, Mohapatra S, Singh D
… +3 more, Joshi V, Singh V, Basu S
Am J Ophthalmol
· 2026 Jun · PMID 42372932
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PURPOSE: To have a comprehensive overview of the current and emerging therapeutic strategies for corneal scarring, focused on various topical pharmacological agents, cell based and cell free therapies, and bioengineered...PURPOSE: To have a comprehensive overview of the current and emerging therapeutic strategies for corneal scarring, focused on various topical pharmacological agents, cell based and cell free therapies, and bioengineered stromal substitutes as alternatives to traditional corneal transplantation. DESIGN: Perspective review. METHODS: A comprehensive literature search was conducted to identify relevant studies on corneal scaring, associated pathophysiology, and the treatment modalities We also screened the reference lists of relevant articles and reviews. Emphasis was placed on topical anti-inflammatory and antifibrotic therapies, cell-based therapies and their secretome and EVs, advances in biomaterials, hydrogels, and three-dimensional bioprinting for stromal reconstruction. RESULTS: Corneal scarring results from dysregulated wound healing, characterized by myofibroblast differentiation and disorganized extracellular matrix deposition. Conventional therapies provide limited and short-term benefits. Emerging antifibrotic agents, such as losartan and Decorin, target key profibrotic pathways and show therapeutic potential. Cell-free approaches, including conditioned media, exosomes, and microRNA-based strategies, have anti-inflammatory and regenerative effects without the limitations of cell transplantation. Mesenchymal stem cells have efficient paracrine-mediated immunomodulatory properties, although challenges in standardization and clinical translation remain. Biomaterial-based strategies, including collagen scaffolds, decellularized matrices, hydrogels, and 3D bioprinting, are being developed as alternatives for corneal repair. CONCLUSION: Recent advancements in regenerative medicine and bioengineering provide viable alternatives to corneal transplantation reliant on donors. Although these techniques have some preclinical success, more standardization, safety validation, and extensive clinical studies are necessary to confirm their long-term efficacy and facilitate routine clinical implementation in corneal scar treatment.
Am J Ophthalmol
· 2026 Jun · PMID 42365872
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PURPOSE: Recipients of solid organ transplants (SOT) undergo long-term immunosuppressive therapy, placing them at a high risk for developing skin cancer. Given that the conjunctiva and skin share key risk factors for neo...PURPOSE: Recipients of solid organ transplants (SOT) undergo long-term immunosuppressive therapy, placing them at a high risk for developing skin cancer. Given that the conjunctiva and skin share key risk factors for neoplasia, we conducted a study to examine the association between immunosuppressive agents used in recipients of SOT and risk of ocular surface neoplasia (OSSN). DESIGN: Retrospective cohort study using the TriNetX US Collaborative Network. PARTICIPANTS AND CONTROLS: We included individuals ≥ 18 years of age receiving oral or intravenous tacrolimus, cyclosporine, sirolimus, mycophenolate mofetil or sodium, everolimus, or azathioprine. Individuals without subsequent ophthalmology follow-up or with prior OSSN diagnoses were excluded. The control cohort included individuals with multiple ophthalmology follow-ups, no prior OSSN diagnoses, and no exposure to the medications of interest. METHODS: Propensity score matching (1:1) was used to control for covariates such as demographics and known risk factors of OSSN. Odds ratios with 95% confidence intervals were calculated using univariate analysis to compare outcomes. Multiple sub analyses were performed, in which we required additional exposure to the medications, controlled for common autoimmune disorders, or excluded all recipients of SOT. MAIN OUTCOME MEASURES: Risk of a new OSSN diagnosis during the study period. RESULTS: After matching, 43,580 individuals were included for analysis. There were 46 (0.11%) new cases of OSSN in the exposure cohort and 20 (0.05%) cases in the control cohort. Those on immunosuppressive therapy had a 2.3 times higher risk of developing OSSN (odds ratio [OR] 2.30 [95% CI 1.36 to 3.89]) during the study period. Sensitivity analyses requiring additional instances of medication exposure (OR 3.67 [95% CI 1.94 to 6.95]) or controlling for other indications of immunosuppressive therapy (OR 1.70 [95% CI 1.06 to 2.74]) showed consistent results. Excluding all recipients of SOT resulted in no significant association with OSSN (OR 1.31 [95% CI 0.64 to 2.69]). CONCLUSIONS: Recipients of SOT who undergo immunosuppressive therapy experienced a significantly increased risk of developing OSSN. Appropriate ophthalmological monitoring for OSSN in these populations is recommended.
Teo KYC, Gilead N, Jiang Z
… +8 more, Chong YJ, Tan A, Chan HH, Ibrahim FNI, Fenner BJ, Ong C, Sun C, Cheung CMG
Am J Ophthalmol
· 2026 Jun · PMID 42365871
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OBJECTIVE: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fl...OBJECTIVE: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT. DESIGN: Image analysis of a double-masked, sham-controlled, randomized clinical trial. SUBJECTS: 55 eyes of 55 treatment-naïve participants with symptomatic macular PCV completing 52 weeks of follow-up. METHODS: Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52. MAIN OUTCOME MEASURES: Longitudinal OCTA changes and predictors of PL closure at week 52. RESULTS: We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72±3.01mm at baseline, 2.86±2.50mm at week 12, 3.59±3.26mm at week 52; monotherapy: 3.77±2.23mm at baseline, 3.27±2.36mm at week 12, and 3.47±2.58mm at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29±2.08 mm at baseline, 1.46±1.36mm at week 12, and 1.53±1.32mm at week 52; monotherapy: 2.39±1.85mm at baseline, 1.87±1.68mm at week 12, and 1.82±1.38mm at week 52). BNN VD reduction was greater in the combination arm at week 12 (-10±15% vs -3±12%, p=0.02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52). In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (β=-0.96 [-1.21 to -0.72], p<0.01), and baseline CST predicted CST change (β=0.93 [0.75 to 1.10], p<0.01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], p=0.03). CONCLUSIONS: Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as non-invasive biomarkers for predicting treatment response in PCV.
Oh GJ, Reddy RY, Shiuey EJ
… +4 more, Mahmoudzadeh R, Rapuano CJ, Klufas MA, Syed ZA
Am J Ophthalmol
· 2026 Jun · PMID 42364707
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PURPOSE: To analyze the relationship between intraoperative and post-penetrating keratoplasty (PK) posterior segment variables and PK graft survival. DESIGN: Retrospective clinical cohort study. SUBJECTS: Patients underg...PURPOSE: To analyze the relationship between intraoperative and post-penetrating keratoplasty (PK) posterior segment variables and PK graft survival. DESIGN: Retrospective clinical cohort study. SUBJECTS: Patients undergoing PK between May 1, 2007 and September 1, 2018 at a single tertiary center. METHODS: Chart review for PKs performed was conducted, and the first PK completed at the institution for each patient was included for analysis. Data collected included demographics, medical and ocular history, preoperative and intraoperative findings, and intraoperative and postoperative posterior segment factors (pars plana vitrectomy [PPV], endolaser, retinal detachment [RD], and vitreous hemorrhage [VH]). After univariable analysis, variables were selected for multivariable Cox regression analysis. MAIN OUTCOME MEASURE: Graft failure, defined as irreversible and visually significant corneal edema, haze, or scarring. RESULTS: Eight hundred and thirty-five eyes of 835 patients were included. Mean age was 57.1±22.0 (range: 0-100) years, and mean time from PK to final follow-up or graft failure was 3.2±2.9 (range: 0.01-16.1) years. Graft failure occurred in 35.0% of cases with a mean onset of 1.9±2.0 (range: 0.04-11.4) years after PK. After multivariable analysis, nine variables had significant associations with failure. Two posterior segment variables were significant: intraoperative VH at the time of PK (hazard ratio [HR] 6.6, 95% confidence interval [CI] 1.6-27.7, p=0.010) and silicone oil (SO) tamponade after the PK (HR 3.2, 95% CI 1.4-7.4, p=0.007). CONCLUSIONS: Graft failure is a serious complication of PK. VH at the time of the PK and SO tamponade after the PK were associated with graft failure. In complex eyes that are undergoing PK grafts and that may also require posterior segment interventions, these findings may guide patient counseling and discussion of graft prognosis.
Altamirano F, Yuan M, Chaaya C
… +10 more, Hoyek S, Jeon JH, Alahmadi R, Mantagos IS, Wu C, Berrocal AM, Gonzalez E, VanderVeen DK, Gise R, Patel NA
Am J Ophthalmol
· 2026 Jun · PMID 42364706
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OBJECTIVE: To characterize rates, timing, and predictors of retinopathy of prematurity (ROP) retreatment among infants treated with primary laser or intravitreal bevacizumab injection. DESIGN: Retrospective consecutive,...OBJECTIVE: To characterize rates, timing, and predictors of retinopathy of prematurity (ROP) retreatment among infants treated with primary laser or intravitreal bevacizumab injection. DESIGN: Retrospective consecutive, comparative clinical study. PARTICIPANTS: Infants who underwent initial treatment for treatment-warranted ROP (TW-ROP) with either intravitreal bevacizumab or laser photocoagulation between 2017-2023. METHODS: Patients were stratified into two treatment groups: primary laser group vs primary bevacizumab group. MAIN OUTCOME MEASURES: Retreatment within the first 3 months (0-90 days) was assessed and classified as early (≤30 days) or late (31-90 days). RESULTS: 238 eyes of 122 infants were treated for ROP; of those, 181 (76.1%) eyes of 93 (76.2%) patients were included. There were 116 (64.1%) eyes in the bevacizumab group, and 65 (35.9%) eyes in the laser group. 33 (18.2%) eyes - all micro- or nano-premature (<27 weeks GA and/or <800 grams) - required retreatment for TW-ROP. 16 (8.8%) required early retreatment at a median postmenstrual age (PMA) of 40.4 weeks (IQR, 38.44-43.3). There were differences in the proportion of early retreated infants (21.5% for laser vs 1.7% for injection, p<0.001). 17 (9.4%) eyes required late retreatment. The median PMA at late retreatment was 45.6 weeks (IQR, 43.7-47.4). Infants in the bevacizumab group had lower odds of retreatment within three months than those with laser (OR, 0.23; 95%CI, 0.06-0.82). Similarly, patients in the bevacizumab group had lower odds of requiring early retreatment compared to those with laser (OR, 0.08; 95%CI, 0.04-0.18). Within eyes with retreatment, infants in the bevacizumab group had a later PMA at retreatment than those in the laser group (B=6.81; 95%CI: 4.68-8.93). AROP was associated with earlier PMA at retreatment (B=-7.72; 95%CI, -9.36 to -6.10). CONCLUSION: In this study, early retreatment was low (8.8%), with most eyes initially treated with laser (21.5%) rather than bevacizumab (1.7%). Aggressive ROP was associated with earlier retreatment, highlighting its role as a marker of more severe disease. Compared to laser, bevacizumab was associated with lower overall and early retreatment, and delayed need for additional intervention when necessary. All retreatments occurred in micro- or nano-premature infants, suggesting that medium-to-low risk infants may require less strict post-treatment monitoring.
Hafezi F, Akcan RE, Kling S
… +8 more, Kollros L, Depczyńska M, Awwad S, Knyazer B, Hafezi N, Blaser F, Hillen M, Torres-Netto EA
Am J Ophthalmol
· 2026 Jun · PMID 42364705
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PURPOSE: To evaluate the safety and efficacy of a second-generation individualized corneal cross-linking (CXL) protocol (ELZA-sub400) using high-fluence UV-A irradiation in ultrathin ectatic corneas. DESIGN: Retrospectiv...PURPOSE: To evaluate the safety and efficacy of a second-generation individualized corneal cross-linking (CXL) protocol (ELZA-sub400) using high-fluence UV-A irradiation in ultrathin ectatic corneas. DESIGN: Retrospective, single-centre, consecutive interventional case series. METHODS: Twenty-nine eyes of 24 patients with progressive keratoconus or post-LASIK ectasia and a post-soak intraoperative thinnest stromal thickness <400 µm were included. After epithelial removal and riboflavin soaking, continuous UV-A irradiation (365 nm) at 3 or 9 mW/cm² was delivered with total fluence titrated up to 10 J/cm² based on intraoperative ultrasound pachymetry and a previously published nomogram targeting an uncross-linked stromal margin of approximately 70 µm above the endothelium. Outcomes were assessed at baseline and up to 12 months using corrected distance visual acuity (CDVA) and corneal parameters measured using Scheimpflug tomography and anterior segment OCT (AS-OCT) with Placido-based topography. The main outcome measure was the proportion of eyes without progression at 12 months, defined as <1.0 D increase in maximum keratometry (Kmax). Secondary outcomes included changes in CDVA, refraction, Kmax, stromal thickness, demarcation line depth, densitometry, and safety parameters. RESULTS: At 12 months, 22/29 eyes (76%; 95% CI, 57.9%-87.8%) met the non-progression criterion. Mean change in Kmax was -0.77 ± 5.10 D (95% CI, -2.71 to 1.17; p=0.418). Mean demarcation line-to-anterior stroma distance was 205 ± 64 µm (95% CI, 180.7-229.3), and demarcation line-to-endothelium distance was 64 µm (IQR, 49-152). All demarcation lines remained within the stromal layer; 15/29 eyes (51.7%) had a demarcation line located ≤70 µm from the endothelium. Median CDVA changed from 0.10 to 0.32 logMAR (p=0.142). Minimum stromal thickness showed a median change of 4.0 µm (p=0.309). No significant change was observed in densitometry, and no eye developed deep stromal haze or endothelial decompensation. CONCLUSIONS: Second-generation ELZA-sub400 CXL halted ectasia progression in 76% of ultrathin corneas at 12 months and was associated with an acceptable short-term safety profile, including stromal-confined demarcation line formation and no observed endothelial decompensation. The numerical decline in spectacle CDVA observed in this severely affected cohort did not reach statistical significance but is clinically important and warrants confirmation in larger prospective studies.
Woreta FA, Aamir FB, Ali M
… +6 more, Culican S, Wang J, Dun C, Martin B, Schnabel S, Bartley GB
Am J Ophthalmol
· 2026 Jun · PMID 42349536
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PURPOSE: To evaluate the characteristics of the American Board of Ophthalmology (ABO) oral board examiners and examinees as well as trends in examiner and examinee gender over time. DESIGN: Retrospective cohort study SUB...PURPOSE: To evaluate the characteristics of the American Board of Ophthalmology (ABO) oral board examiners and examinees as well as trends in examiner and examinee gender over time. DESIGN: Retrospective cohort study SUBJECTS: ABO oral board examiners and examinees METHODS: We utilized data from the American Board of Ophthalmology (ABO) and Association of American Medical Colleges (AAMC) to assess board examiner and examinee demographic characteristics from 2011 to 2024. Examiner characteristics included gender, years of experience, initial certification year and average examiner score. Examinee characteristics included gender, years since residency graduation and exam outcome (pass/fail). We utilized logistic regression to examine temporal trends in examiner and examinee gender from 2013 to 2024. MAIN OUTCOME MEASURES: Gender distribution of examiners and examinees. RESULTS: Overall, the proportion of women examiners increased over the study period. Notably, the most pronounced increase occurred following the transition from in-person to virtual oral board exam administration in 2020, rising from 31.3% (95% CI: 24.1-38.4%) in 2019 to 49.1% (95% CI: 43.8-54.4% in 2024 (p<.001). The percentage of women examinees remained stable [41.7% (95% CI: 37.6-45.8%) in 2019; 37.5% (95% CI: 33.0-42.0%) in 2024, p-value: .019]. CONCLUSIONS: The representation of women among the ABO oral board examiners has increased significantly following the transition to virtual exams while the proportion of examinees remained stable. Strategies to increase flexibility in scheduling exams may be beneficial in continuing to improve examiner representation.
Yazji IH, Abbass NJ, Kaelber DC
… +2 more, Talcott KE, Singh RP
Am J Ophthalmol
· 2026 Jun · PMID 42341975
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PURPOSE: PCSK9 inhibitors (PCSK9i) are a newer class of lipid-lowering drug that may be effective at lowering risk for retinal artery (RAO) and retinal vein occlusion (RVO). This study aims to investigate this relationsh...PURPOSE: PCSK9 inhibitors (PCSK9i) are a newer class of lipid-lowering drug that may be effective at lowering risk for retinal artery (RAO) and retinal vein occlusion (RVO). This study aims to investigate this relationship between PCSK9i use and retinal vascular occlusion among patients with hyperlipidemia. DESIGN: Retrospective, comparative clinical cohort study SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: : Patients with hyperlipidemia, defined as serum LDL level of ≥130 mg/dL and total cholesterol level of ≥220 mg/dL, that were prescribed a lipid-lowering medication were identified. Patients prescribed a PCSK9i were included in the study group and were compared to control patients prescribed any other type of lipid-lowering drug. METHODS: This study was conducted utilizing electronic health record data from health organizations in the United States through the TrinetX platform. Propensity-score matching (PSM) was completed based on relevant patient demographics, comorbidities, and lab values. Comparison of main outcomes between the PCSK9i and non-PCSK9i groups was performed using measures of association analysis to determine risk ratio (RR) with 95% confidence intervals (CI). MAIN OUTCOME MEASURES: The outcomes measured consisted of occurrence of retinal vascular occlusion, RAO, RVO, central RAO, and central RVO at 3-year, 5-year, and 7-year time points. RESULTS: Following PSM, a total of 12,960 patients were included in each cohort. The analysis revealed the PCSK9i cohort had a significantly lower risk for development of retinal vascular occlusions at multiple points, including 3-year (RR 0.56, CI 0.39-0.79), 5-year (RR 0.50, CI 0.37-0.67) and 7-year time points (RR 0.46, CI 0.35-0.61). This lower risk was also seen in the PCSK9i group for an outcome of RVO at 5-years (RR 0.50, CI 0.34-0.73) and 7-years (RR 0.47, CI 0.33-0.67). For occurrence of RAOs (RR 0.47, CI 0.30-0.76) and CRVO (RR 0.46, CI 0.29-0.74) separately, the PCSK9i cohort had a lower risk at 7 years. CONCLUSION: These findings suggest that PCSK9i may reduce the risk of retinal vascular occlusion compared to other classes of lipid-lowering medications. PRéCIS: Patients prescribed PCSK9 inhibitors had a significantly lower risk of developing retinal vascular occlusions, including venous and arterial occlusions, over seven years compared to those on other lipid-lowering therapies, suggesting protective microvascular effects.
Am J Ophthalmol
· 2026 Jun · PMID 42341974
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IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renew...IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium, one of the most rapidly proliferating tissues in the body. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with corneal epithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy (PE; graded as absent, mild, moderate, or severe/complicated) and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time (TBUT), and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group versus 4.7% in the AI group and 2.3% in controls (χ² = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, TBUT, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of punctate epitheliopathy and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Among respondents, symptom scores were uniformly low; however, the incomplete OSDI response rate in the CDKAI group limits definitive conclusions regarding symptom burden. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.