A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation.

Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1. We further confirm the TCF4 locus in GWAS for admixed African and Hispanic/Latino ancestries and show an enrichment of European-ancestry haplotypes at TCF4 in FECD cases. Among the novel associations are low frequency missense variants in laminin genes LAMA5 and LAMB1 which, together with previously reported LAMC1, form laminin-511 (LM511). AlphaFold 2 protein modeling, validated through homology, suggests that mutations at LAMA5 and LAMB1 may destabilize LM511 by altering inter-domain interactions or extracellular matrix binding. Finally, phenome-wide association scans and colocalization analyses suggest that the TCF4 CTG18.1 trinucleotide repeat expansion leads to dysregulation of ion transport in the corneal endothelium and has pleiotropic effects on renal function.

Reticular Bullous Epithelial Corneal Edema after Netarsudil Use for Elevated Intraocular Pressure with Concurrent Fuchs Endothelial Corneal Dystrophy: A Case Report.

Introduction: We describe a case of reticular bullous corneal epithelial edema associated with the use of netarsudil ophthalmic solution (0.02%) for elevated intraocular pressure. Case Presentation: A 74-year-old man with a complex ocular medical history, including Fuchs dystrophy and primary open-angle glaucoma, developed progressively worsening loss of vision 3 weeks following the initiation of topical netarsudil for increased intraocular pressure. Visual acuity in the left eye was counting fingers at 3 feet and intraocular pressure in the left eye was 7 mm Hg. A characteristic "honeycomb" pattern epitheliopathy was seen on ocular examination. Conclusion: Reticular bullous epithelial corneal edema is an uncommon finding associated with netarsudil use, which can be overlooked in favor of corneal edema associated with Fuchs dystrophy. This is especially relevant given Fuchs dystrophy itself is a predisposing risk factor for netarsudil-induced reticular bullous corneal epithelial edema. Improvement of both the corneal edema and visual acuity should be expected after discontinuing netarsudil and undergoing superficial keratectomy.

Impact of scleral tunnel length on the position of IOLs in flanged intrascleral haptic fixation.

PURPOSE: To investigate the effect of scleral tunnel length on the effective lens position and tilt of the intraocular lens (IOL) in flanged intrascleral haptic fixation (ISHF) using anterior segment optical coherence tomography (AS-OCT). SETTING: Tertiary institution. DESIGN: Retrospective case-control study. METHODS: This study included 55 and 42 eyes that underwent ISHF with 1.0- and 2.0-mm scleral tunnels, respectively. Twenty-three eyes that underwent sutured fixation were used as a control. The anterior chamber depth (ACD), scleral tunnel length, incident angle of haptic, and tilting of optic were analyzed using AS-OCT. RESULTS: The mean postoperative ACD, vertical tilt angle, and spherical equivalent of the 1.0-mm were 5.27 ± 0.39 mm, 6.04 ± 4.87°, and 0.38 ± 1.03 D, respectively. The ACD and vertical tilt angle of the 1.0-mm were larger than those of the others (p<0.001 and p<0.05, respectively), and the postoperative spherical equivalent was more hyperopic (p<0.05). The 2.0-mm exhibited a lower frequency of tilting greater than 7°. The inter-eye difference in ACD between in-the-bag fixation and ISHF of the1.0-mm tunnel was significantly greater than that in the 2.0-mm tunnel (p<0.05). The 1.0 mm tunnel had a significantly larger incident angle and a longer tunnel length (p<0.001, respectively) and showed a greater difference in the tunnel length on both sides (p<0.05). CONCLUSION: A shorter tunnel yielded a more unstable IOL position, greater variation in angle and tunnel length, and longer ACD during ISHF. An exact 2.0-mm tunnel must be created on both sides to achieve a stable and predictable IOL position.

Axial length and pharmacologic pupillary dilation in highly myopic patients.

PURPOSE: To determine how high myopia impacts pharmacological pupillary dilation, and to evaluate the relationship between the extent of pharmacologic pupillary dilation and axial length. METHODS: Patients were grouped into high myopes, defined as one or both eyes having a refractive error greater than - 6 diopters, and controls (between - 2 and + 2 diopters). Dilation was achieved with 1 drop each of tropicamide 1% and phenylephrine 2.5%. Pupil size was measured at full and dim light prior to dilation, then 15 and 30 min after dilation. Biometry was measured for each patient. Statistical analyses were performed using the Mann-Whitney-Wilcoxon tests, two-sample Welch's t-tests, and linear mixed effect models and generalized estimating equations models accounting for inter-eye correlation. RESULTS: Forty patients (20 high myopes and 20 controls, 80 eyes total) participated in the study. High myopes had larger pupils at baseline and achieved significantly greater pupillary size (7.08 mm, 95% CI: 6.97 to 7.19 mm) than controls (6.23 mm, 95% CI: 5.94 to 6.52 mm) after 30 min of dilation (P < .0005). Fully dilated pupil size at 30 min was significantly correlated with both refractive error (r = - 0.57, P < .0005) and axial length (r = 0.47, P < .0005). Generalized estimating equations and linear mixed effect models identified other predictive variables of pupil size after dilation including age and white-to-white diameter. CONCLUSIONS: Highly myopic patients dilate to a larger pupillary size compared to other patients. Predicting dilation based on extent of myopia could facilitate intraocular surgery planning and reduce clinic wait times for myopic patients.

Intracameral antibiotics during cataract surgery: efficacy, safety, and cost-benefit considerations.

PURPOSE OF REVIEW: We summarize evidence-based considerations regarding the use of intracameral antibiotics during cataract surgery. RECENT FINDINGS: The use of intraoperative intracameral antibiotics reduced the incidence of postcataract surgery endophthalmitis 3.5-fold, with an odds ratio ranging from 0.14 to 0.19. A survey of the American Society of Cataract and Refractive Surgery showed usage of intracameral injections of antibiotics increased by 16% in the United States between 2014 and 2021. The frequency of vancomycin usage has sharply dropped to 6%, while moxifloxacin is now the dominant choice at 83% among respondents. One analysis showed that 2500 patients need to be treated with intracameral antibiotics to prevent one case of endophthalmitis. A 500 µg intracameral moxifloxacin at $22 dollars per dose is cost-effective, including for patients with posterior capsular rupture (PCR). SUMMARY: Studies substantiate the safety and efficacy of intracameral antibiotics for endophthalmitis prophylaxis. Intracameral moxifloxacin and cefuroxime are the most common choices. While vancomycin shows potential for efficacy, further studies evaluating clinical outcomes are needed. Adverse events are rare and commonly due to errors in preparation. Topical antibiotics do not provide additional prophylactic benefits to intracameral regimens. Intracameral antibiotics given alone are cost-effective.

Oxidative stress and antioxidants in cataract development.

PURPOSE OF REVIEW: Oxidative stress plays a central role in cataract pathogenesis, a leading cause of global blindness. This review delves into the role of oxidative stress in cataract development and key biomarkers - glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) - to clarify their functions and potential applications in predictive diagnostics and therapies. RECENT FINDINGS: Antioxidants serve as pivotal markers in cataract pathogenesis. GSH affects the central lens due to factors such as enzyme depletion and altered connexin expression, impairing GSH diffusion. Age-related oxidative stress may hinder GSH transport via connexin channels or an internal microcirculation system. N-acetylcysteine, a GSH precursor, shows promise in mitigating lens opacity when applied topically. Additionally, SOD, particularly SOD1, correlates with increased cataract development and gel formulations have exhibited protective effects against posterior subscapular cataracts. Lastly, markers of lipid peroxidation, MDA and 4-HNE, have been shown to reflect disease severity. Studies suggest a potential link between 4-HNE and connexin channel modification, possibly contributing to reduced GSH levels. SUMMARY: Oxidative stress is a significant contributor to cataract development, underscoring the importance of antioxidants in diagnosis and treatment. Notably, GSH depletion, SOD decline, and lipid peroxidation markers are pivotal factors in cataract pathogenesis, offering promising avenues for both diagnosis and therapeutic intervention.

Light adjustable intraocular lenses in cataract surgery: considerations.

PURPOSE OF REVIEW: Light adjustable intraocular lens (LAL) is a promising concept in cataract surgery. This review explores considerations for the use of LALs. RECENT FINDINGS: Through updates, the safety of LALs and light delivery devices have been enhanced, enabling more efficient treatment with lower ultraviolet (UV) energy. Preoperative topography and aberration are essential for understanding indications for LALs. Furthermore, when determining intraocular lens power, it is crucial to factor in potential postoperative myopia or hyperopic adjustments. This is achieved by establishing a proper postimplantation refractive target and considering potential wavefront changes. Postoperative adjustments for defocus and astigmatism have demonstrated excellent outcomes. Monovision strategy by adjustable blended vision of LALs revealed distance vision of 20/20 along with near vision of J2 in 96% of patients. However, the results of clinical studies on postrefractive cataract surgery showed contrasting outcomes at distance, indicating the need for further research results regarding its effectiveness. A new postoperative workflow needs to be designed to enable a systematic follow-up process. SUMMARY: LALs are safe and demonstrate promising refractive outcomes. To achieve appropriate results, understanding the changes in optical characteristics associated with adjustment and constructing a new postoperative workflow are necessary.

The effect of patient age on some new and older IOL power calculation formulas.

PURPOSE: To assess the accuracy of intraocular lens (IOL) power calculation in different age groups using various IOL calculation formulas. METHODS: Data from 421 eyes of 421 patients ≥60 years old (ages: 60-69, n = 131; 70-74, n = 105; 75-84, n = 158 and ≥85, n = 27), who underwent uneventful cataract surgery with SN60WF IOL implantation at John A. Moran Eye Center, Salt Lake City, USA, were retrospectively obtained. The SD of the prediction error (PE), median and mean absolute PEs and the percentage of eyes within ±0.25, ±0.50, ±0.75 and ±1.00 D were calculated after constant optimizations for the following formulas: Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO) 2.0, Haigis, Hoffer Q, Hoffer QST, Holladay 1, Kane, Radial Basis Function (RBF) 3.0 and SRK/T. Results were compared between the different age groups. RESULTS: Predictability rates within 0.25D were lower for the eldest age group compared with the other groups using the EVO 2.0 (33% vs. 37%-53%, p = 0.045), Kane (26% vs. 35%-50%, p = 0.034) and SRK/T (22% vs. 31%-49%, p = 0.002). Higher median absolute refractive errors for all formulas were observed in the oldest group [range: 0.39 D (Haigis, Hoffer QSR)-0.48 D (Kane)], followed by the youngest group [range: 0.30 D (RBF 3.0)-0.39 D (Holladay 1, SRK/T)] but did not reach statistical significance. No significant differences between the groups in the distribution parameter were seen. CONCLUSION: Current IOL power calculation formulas may have variable accuracy for different age groups. This should be taken into account when planning cataract surgery to improve refractive outcomes.

Cost-Effectiveness Analysis of Light Adjustable Lens Compared to Monofocal Intraocular Lens in Cataract Surgery.

PURPOSE: To analyze the cost-effectiveness of the Light Adjustable Lens (LAL; RxSight) in comparison to a monofocal intraocular lens (IOL) for individuals undergoing cataract surgery in both eyes. METHODS: A cost-effectiveness analysis was performed using a Markov model that simulated the patient outcomes and costs associated with undergoing cataract surgery with the LAL or monofocal IOL. Cost-effectiveness was determined using the incremental cost-effectiveness ratio (ICER), a measure that quantifies the incremental cost in dollars per quality-adjusted life year (QALY) gained. Treatments with the ICER below the willingness-to-pay threshold (WTP) of $50,000/QALY were considered cost-effective. The model was also evaluated for the impact of uncertainties in parameters using one-way sensitivity and probabilistic sensitivity analyses. RESULTS: The cost-effectiveness analysis showed that the LAL is cost-effective compared to monofocal IOLs in patients undergoing cataract surgery, with ICERs of $9,792/QALY (health care perspective) and $10,072/QALY (societal perspective) both significantly below the WTP. The model was most sensitive to patient age, market cost of the LAL, and proportion of patients with residual astigmatism following cataract surgery. The probabilistic sensitivity analysis showed that cataract surgeries in patients starting at age 65 years were cost-effective in 94% of the simulations at a WTP of $50,000/QALY. CONCLUSIONS: From both health care and societal perspectives, the study shows cataract surgeries performed with the LAL are cost-effective when compared to those performed with a monofocal IOL. More studies are needed to compare the LAL to other premium lenses that also provide patients with excellent visual outcomes at a higher cost. [J Refract Surg. 2023;39(11):777-782.].

Evaluating the accuracy of a cataract surgery simulation video in depicting patient experiences under conscious anesthesia.

PURPOSE: To evaluate the accuracy of a point-of-view cataract surgery simulation video in representing different subjective experiences of patients undergoing the procedure. METHODS: One hundred consecutive post-cataract-surgery patients were shown a short simulation video of the surgery obtained through a porcine eye model during the first postoperative week. Patients then answered a multiple-choice questionnaire regarding their visual and tactile intraoperative experiences and how those experiences matched the simulation. RESULTS: Of the patients surveyed (n = 100), 78% (n = 78) recalled visual experiences during surgery, 11% recalled pain (n = 11), and 6.4% (n = 5) recalled frightening experiences. Thirty-six percent of patients (n = 36) were interviewed after their second cataract surgery; there was no statistically significant difference between anxiety scores reported before the first eye surgery and second eye surgery (p = 0.147). Among all patients who recalled visual experiences (n = 78), nearly half (47.4%) reported that the video was the same/similar to their experience. Forty-eight percent of the patients recommended future patients to watch the video before their procedures, and more than a third (36%) agreed that watching the video before surgery would have helped them to relax. CONCLUSIONS: Our model reflects the wide range of subjective patient experiences during and after surgery. The high percentage of patients who found the video accurate in different ways suggests that, with more development, point-of-view cataract simulation videos could prove useful for educational or clinical use. Further research may be done to confirm the simulation's utility, by screening the video for subjects before operations.

Refractive Changes After Implantation of Reversed Intraocular Lens in Cataract Surgery: A Mathematical Model.

PURPOSE: To develop a mathematical model that can predict the amount of refractive change caused by implantation of an intraocular lens (IOL) in a reversed position during cataract surgery. METHODS: A theoretical mathematical formula based on the Gullstrand eye model was constructed to estimate the refractive change of the eye after implantation of a reversed IOL. The refractive change caused by implantation of the IOL in a reversed position was calculated based on the exchange of the anterior curvature with the posterior curvature of the IOL, and the lengthening of the distance between the IOL and the retina. In case of a three-piece IOL with angulation, the amount of refractive change was calculated based on its angle and the total refractive power of the eye, which is dependent on the focal length of the eye. RESULTS: Calculated refractive change for one-piece IOLs was less than 0.10 diopter (D). For three-piece IOLs, the calculated refractive change makes the eye on average 0.77 D more myopic and can increase with the total refractive power of the patient's eye. The mathematical model was applied to seven previously published cases of reverse IOL implantation. CONCLUSIONS: This calculation demonstrates that with an upside-down IOL, there is a small refractive change in the one-piece IOL, including a toric IOL without angulation, but there can be a large refractive change in the three-piece IOL with angulation, especially using a higher power IOL or with a shorter axial length. [J Refract Surg. 2023;39(5):326-331.].

Cost-effectiveness analysis of endoscopic dacryocystorhinostomy using Markov modelling.

OBJECTIVE: To determine the cost-effectiveness of endoscopic dacryocystorhinostomy (DCR). METHODS: We constructed a Markov model in which patients with nasolacrimal duct obstruction received endoscopic DCR or no surgery. Incremental cost-effectiveness ratios, 1-way sensitivity analyses, and probabilistic sensitivity analyses were used to evaluate for model sensitivity to multiple model inputs. RESULTS: Endoscopic DCR was found to be cost-effective with an incremental cost-effectiveness ratio of US$2162 per quality-adjusted life-year. The model was most sensitive to the health utility deduction from epiphora. Probabilistic sensitivity analysis found endoscopic DCR to be cost-effective over no surgery 93.7% of the time. CONCLUSIONS: Endoscopic DCR is a cost-effective treatment for patients with epiphora. The model is very sensitive to the negative effect epiphora has on quality of life. With the advancement of health care technology and surgical techniques, the success rates of endoscopic DCR continue to improve and to be an even more efficacious and economical treatment for nasolacrimal duct obstruction.

Ultraviolet light exposure and its penetrance through the eye in a porcine model.

AIM: To determine the amount of ultraviolet (UV) light irradiance that various layers of the eye receive as sunlight passes through the eye, and to investigate the protective benefits of UV light-blocking contact lenses. METHODS: Twenty-four porcine eyes were prepared in one of three ways: isolated cornea, cornea and lens together, or whole eye preparation. UV light irradiance was measured with a UV-A/B light meter before and after the eye preparations were placed over the meter to measure UV light penetration in each eye structure. In the whole eye preparation, a hole was placed in the fovea to measure light as it passed through the vitreous. Subsequently, UV-protective contact lenses were placed over the structures, and UV light penetrance was measured. Measurements of UV light exposure were taken outdoors at various locations and times. RESULTS: Cornea absorbed 63.56% of UV light that reached the eye. Cornea and lens absorbed 99.34% of UV light. Whole eye absorbed 99.77% of UV light. When UV-protective contact lenses were placed, absorption was 98.90%, 99.55%, and 99.87%, respectively. UV light exposure was dependent on directionality and time of day, and was greatest in areas of high albedo that reflect significant amounts of light, such as a beach. CONCLUSION: Cornea absorbs the majority of UV light that reaches the eye in this model. UV-protective contact lenses reduce UV exposure to the eye. Locations with high albedo expose the eye to higher levels of UV light.

Role of FGF10/FGFR2b Signaling in Homeostasis and Regeneration of Adult Lacrimal Gland and Corneal Epithelium Proliferation.

Purpose: Fibroblast growth factor 10 (FGF10) is involved in eye, meibomian, and lacrimal gland (LG) development, but its function in adult eye structures remains unknown. This study aimed to characterize the role of FGF10 in homeostasis and regeneration of adult LG and corneal epithelium proliferation. Methods: Quantitative reverse transcription PCR was used for analysis of FGF10 expression in both early postnatal and adult mouse LG, and RNA sequencing was used to analyze gene expression during LG inflammation. FGF10 was injected into the LG of two mouse models of Sjögren's syndrome and healthy controls. Flow cytometry, BrdU cell proliferation assay, immunostaining, and hematoxylin and eosin staining were used to evaluate the effects of FGF10 injection on inflammation and cell proliferation in vivo. Mouse and human epithelial cell cultures were treated with FGF10 in vitro, and cell viability was assessed using WST-8 and adenosine triphosphate (ATP) quantification assays. Results: The level of Fgf10 mRNA expression was lower in adult LG compared to early postnatal LG and was downregulated in chronic inflammation. FGF10 injection into diseased LGs significantly increased cell proliferation and decreased the number of B cells. Mouse and human corneal epithelial cell cultures treated with FGF10 showed significantly higher cell viability and greater cell proliferation. Conclusions: FGF10 appears to promote regeneration in damaged adult LGs. These findings have therapeutic potential for developing new treatments for dry eye disease targeting the ability of the cornea and LG to regenerate.

Advances in drug therapy and delivery for cataract treatment.

PURPOSE OF REVIEW: Cataract is one of the leading causes of blindness worldwide and surgery is the only available treatment. Pharmacological therapy has emerged as a potential approach to combat the global shortage of surgery due to a lack of access and resources. This review summarizes recent findings in pharmacological treatment and delivery, focusing on drugs that target oxidative stress and the aggregation of crystallins. RECENT FINDINGS: Antioxidants and oxysterols have been shown to improve or reverse lens opacity in cataract models. N-acetylcysteine amide and N-acetylcarnosine are two compounds that have increased bioavailability over their precursors, alleviating the challenges that have come with topical administration. Studies have shown promising results, with topical N-acetylcarnosine clinically decreasing lens opacity. Furthermore, lanosterol, and more recently 5-cholesten-3b,25-diol (VP1-001), have been reported to combat the aggregation of crystallins in vivo and ex vivo . Delivery has improved with the use of nanotechnology, but further research is needed to solidify these compounds' therapeutic effects on cataracts and improve delivery methods to the lens. SUMMARY: Although further research in drug dosage, delivery, and mechanisms will need to be conducted, pharmacologic therapies have provided new strategies and treatments for the reversal of cataracts.