The effect of citicoline oral solution on quality of life in patients with glaucoma: the results of an international, multicenter, randomized, placebo-controlled cross-over trial.

PURPOSE: This study aims to evaluate whether the use of citicoline oral solution could improve quality of life in patients with chronic open-angle glaucoma (OAG). DESIGN: Randomized, double-masked, placebo-controlled, cross-over study was used. Patients were randomized to one of the two sequences: either citicoline 500 mg/day oral solution-placebo or placebo-citicoline 500 mg/day oral solution. Switch of treatments was done after 3 months; patients were then followed for other 6 months. Follow-up included 3-month, 6-month, and 9-month visits. OUTCOMES: The primary outcome was the mean change of "intra-patient" composite score of the Visual Function Questionnaire-25 (VFQ-25). after citicoline oral solution vs placebo at 6-month visit as compared with baseline. METHODS: The trial was multicenter, conducted at 5 European Eye Clinics. OAG patients with bilateral visual field damage, a mean deviation (MD) ranging from - 5 to - 13 dB in the better eye, and controlled IOP were included. VFQ-25 and SF-36 questionnaires were administered at baseline and at 3-, 6-, and 9-month visits. A mixed effect model, with a random effect on the intercept, accounted for correlations among serial measurements on each subject. RESULTS: The primary pre-specified outcome of the analysis reached statistical significance (p = 0.0413), showing greater improvement after citicoline oral solution. There was an increase in the composite score in both arms compared to baseline, but it was significant only for the placebo-citicoline arm (p = 0.0096, p = 0.0007, and p = 0.0006 for the three time-points compared to baseline). The effect of citicoline was stronger in patients with vision-related quality of life more affected by glaucoma at baseline. CONCLUSIONS: This is the first placebo-controlled clinical study evaluating the effect of a medical treatment aiming at improving vision-related quality of life in glaucomatous patients.

Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial.

PURPOSE: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation. DESIGN: Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil. PARTICIPANTS: Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. METHODS: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks. MAIN OUTCOME MEASURE: The 52-week endothelial immune rejection rate. RESULTS: Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis. CONCLUSIONS: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.

When Clarity Is Crucial: Regulating Ocular Surface Immunity.

The ocular surface is a unique mucosal immune compartment in which anatomical, physiological, and immunological features act in concert to foster a particularly tolerant microenvironment. These mechanisms are vital to the functional competence of the eye, a fact underscored by the devastating toll of excessive inflammation at the cornea - blindness. Recent data have elucidated the contributions of specific anatomical components, immune cells, and soluble immunoregulatory factors in promoting homeostasis at the ocular surface. We highlight research trends at this distinctive mucosal barrier and identify crucial gaps in our current knowledge.

Cost analysis of eye bank versus surgeon prepared endothelial grafts.

BACKGROUND: Selective lamellar corneal transplantation (keratoplasty) has overtaken full thickness penetrating keratoplasty as the graft choice for endothelial failure. Even more recently eye bank prepared tissues are becoming increasing popular as a way to reduce the risks of tissue loss and stress during endothelial keratoplasty preparation in the surgical theatre. This study compares costs between surgeon and eye bank prepared tissues for Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK). METHODS: Retrospective study conducted at the Royal Liverpool University Hospital including endothelial keratoplasties with a minimum of 6 months follow-up time. Cost analysis included surgical expenses, tissue acquisition fees, cost of patient's ward admission and out-patient expenses, including cost of re-bubbling procedures, costs of visits, anterior segment imaging and optometrist visits within the first 6 months follow-up. RESULTS: Ninety-eight eyes of 98 patients were included in the study of which 42 underwent DSAEK surgery and 56 DMEK surgery. Cost analysis of surgical expenses in the DSAEK group showed a significant difference between using surgeon prepared and eye bank prepared tissue (£3866 ± 296 and £4389 ± 360, respectively; p < 0.01) and the same was found in the DMEK group (£3682 ± 167 and £4162 ± 167 for surgeon prepared and eye bank prepared tissues, respectively; p < 0.01). Cost of out-patient visits did not differ significantly in either group. CONCLUSIONS: At the Royal Liverpool University Hospital, eye bank prepared tissues had higher surgical expenses compared to those prepared by the surgeon, while the post-operative care expenses were similar between the two groups.

Regulatory T cells promote corneal endothelial cell survival following transplantation via interleukin-10.

The functional competence of corneal endothelial cells (CEnCs) is critical for survival of corneal allografts, but these cells are often targets of the immune response mediated by graft-attacking effector T cells. Although regulatory T cells (Tregs) have been studied for their role in regulating the host's alloimmune response towards the graft, the cytoprotective function of these cells on CEnCs has not been investigated. The aim of this study was to determine whether Tregs suppress effector T cell-mediated and inflammatory cytokine-induced CEnC death, and to elucidate the mechanism by which this cytoprotection occurs. Using 2 well-established models of corneal transplantation (low-risk and high-risk models), we show that Tregs derived from low-risk graft recipients have a superior capacity in protecting CEnCs against effector T cell-mediated and interferon-γ and tumor necrosis factor-α-induced cell death compared to Tregs derived from high-risk hosts. We further demonstrate that the cytoprotective function of Tregs derived from low-risk hosts occurs independently of direct cell-cell contact and is mediated by the immunoregulatory cytokine IL-10. Our study is the first to report that Tregs provide cytoprotection for CEnCs through secretion of IL-10, indicating potentially novel therapeutic targets for enhancing CEnC survival following corneal transplantation.

Ocular Surface Side Effects of Novel Anticancer Drugs.

Surgery, anticancer drugs (chemotherapy, hormonal medicines, and targeted treatments), and/or radiation are common treatment strategies for neoplastic diseases. Anticancer drugs eliminate malignant cells through the inhibition of specific pathways that contribute to the formation and development of cancer. Given the ability of such pharmacological medications to combat cancerous cells, their role in the management of neoplastic diseases has become essential. However, these drugs may also lead to undesirable systemic and ocular adverse effects due to cyto/neuro-toxicity and inflammatory reactions. Ocular surface side effects are recognized to significantly impact patient's quality of life and quality of vision. Blepharoconjunctivitis is known to be a common side effect caused by oxaliplatin, cyclophosphamide, cytarabine, and docetaxel, while anastrozole, methotrexate, and 5-fluorouracil can all determine dry eye disease. However, the potential processes involved in the development of these alterations are yet not fully understood, especially for novel drugs currently available for cancer treatment. This review aims at analyzing the potential ocular surface and adnexal side effects of novel anticancer medications, trying to provide a better understanding of the underlying pharmacological processes and useful insights on the choice of proper management.

Recent Advances in Nanotechnology for the Treatment of Dry Eye Disease.

Dry eye disease (DED) incidence is continuously growing, positioning it to become an emergent health issue over the next few years. Several topical treatments are commonly used to treat DED; however, reports indicate that only a minor proportion of drug bioavailability is achieved by the majority of eye drops available on the market. In this context, enhancing drug ability to overcome ocular barriers and prolonging its residence time on the ocular surface represent a new challenge in the field of ocular carrier systems. Therefore, research has focused on the development of multi-functional nanosystems, such as nanoemulsions, liposomes, dendrimers, hydrogels, and other nanosized carriers. These systems are designed to improve topical drug bioavailability and efficacy and, at the same time, require fewer daily administrations, with potentially reduced side effects. This review summarizes the different nanotechnologies developed, their role in DED, and the nanotechnology-based eyedrops currently approved for DED treatment.

Glaucoma, Pseudoexfoliation and Hearing Loss: A Systematic Literature Review.

Purpose: To investigate the relationship between glaucoma, pseudoexfoliation and hearing loss (HL). Methods: A systematic literature search following PRISMA guidelines was conducted using the PubMed, Embase, Scopus and Cochrane databases from 1995 up to 28 August 2023. Results: Thirty studies out of the 520 records screened met the inclusion criteria and were included. Most articles (n = 20) analysed the association between pseudoexfoliation syndrome (XFS) and HL, showing XFS patients to have higher prevalence of sensorineural hearing loss (SNHL) at both speech frequencies (0.25, 0.5, 1 and 2 kHz), and higher frequencies (4 and 8 kHz) compared to controls in most cases. No significant differences in prevalence or level of HL between XFS and pseudoexfoliative glaucoma (XFG) were detected in most studies. Eight articles analysed the relationship between primary open-angle glaucoma (POAG) and HL. Overall, a positive association between the two conditions was highlighted across all studies except for two cases. Similarly, articles focusing on NTG and HL (n = 4) showed a positive association in most cases. The role of autoimmunity and, in particular, the presence of antiphosphatidylserine antibodies (APSA) in patients with NTG and HL suggested an underlying autoimmune or vascular mechanism contributing to their pathogenesis. Only one study analysed the relationship between angle-closure glaucoma (ACG) and HL, showing higher incidence of ACG in patients with SNHL compared to normal hearing controls. Conclusions: Most studies detected an association between XFS and HL as well as POAG/NTG/ACG and HL, suggesting the presence of a similar pathophysiology of neurodegeneration. However, given the strength of the association of XFS with HL, it remains unclear whether the presence of XFG is further associated with SNHL. Further research specifically targeted to assess the correlation between glaucoma, XFS and HL is warranted to provide a more comprehensive understanding of this association.

Endothelial Migration and Regeneration after Penetrating Trauma Injury in a Deep Anterior Lamellar Keratoplasty Graft: Case Presentation and Literature Overview.

Background: Traumatic injuries in eyes previously treated with Deep Anterior Lamellar Keratoplasty (DALK) can lead to ruptures in the Descemet Membrane (DM) and damage to the corneal endothelium, a crucial layer for maintaining corneal clarity. Due to cell cycle constraints, the human corneal endothelium cannot proliferate; instead, it compensates for injury through cell enlargement and migration from adjacent areas. Methods: This study examines a notable case of corneal endothelial cell migration following a penetrating eye injury in a patient previously treated with DALK for keratoconus, supplemented by a review of relevant literature to contextualize the regenerative response. Results: A 39-year-old male with a history of DALK suffered a traumatic eye injury, resulting in damage to the Descemet Membrane and loss of the crystalline lens. After primary repair and considerations for further surgery, the patient's cornea cleared remarkably, with an improved visual acuity. This demonstrates the DM's potential for self-repair through endothelial cell migration. Conclusions: The outcomes suggest that delaying corneal transplant surgery for up to 3 months following Descemet Membrane injury due to ocular trauma could be advantageous. Allowing time for natural healing processes might eliminate the need for further invasive surgeries, thereby improving patient recovery outcomes.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation.

Purpose: To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Design: Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. Participants: The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Methods: Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Main Outcome Measures: Vessel and invasion area of vessels in the corneal graft and host beds. Results: This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P = 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P = 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. Conclusions: In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Descemet membrane endothelial keratoplasty graft detachments in superior versus temporal approach.

PURPOSE: To evaluate the difference in Descemet Membrane Endothelial Keratoplasty (DMEK) graft detachment rate comparing superior versus temporal main incision approach. METHODS: Retrospective comparative study on patients who underwent DMEK surgery for Fuchs endothelial dystrophy or bullous keratopathy with main wound incision performed at either 90° in the superior approach, or at 180°/0° in the temporal approach. All main incisions were secured with a single 10-0 nylon suture at the end of surgery. Data collected were donor age and gender, endothelial cell counts, graft diameter, recipient age and gender, indication for transplant, surgeon grade, re-bubbling rate, air fill in the anterior chamber (AC) at day one and intra- and early postoperative complications. RESULTS: 187 eyes were included in the study. 99 eyes had DMEK surgery with superior approach, while 88 eyes had temporal approach. The two groups had no differences in donor age and sex, endothelial cell counts, graft diameter, recipient age and sex, indication for transplant, surgeon grade, and air fill in the anterior chamber at day one. Re-bubbling rate was 38.4% for surgeries performed with superior access and 29.5% for those with temporal access(p = 0.186). After exclusion of patients with intraoperative and/or postoperative complication, the difference in re-bubbling rate was higher, although non-significant (37.5% and 25% for superior and temporal approach respectively, p = 0.098). CONCLUSION: The temporal approach in DMEK showed a trend towards a clinically significant lower rate of post-operative re-bubbling compared to the superior approach, however, no statistically significant difference was noted comparing the two approaches, which both remain feasible options in DMEK surgery.

Carlevale intraocular lens opacification after Descemet stripping automated endothelial keratoplasty.

PURPOSE: To report a case of sutureless scleral-fixated (SSF) Carlevale intraocular lens (IOL) opacification following Descemet stripping automated endothelial keratoplasty (DSAEK) surgery. METHODS: An 82-year-old man underwent combined SSF Carlevale IOL implant and DSAEK surgery for aphakic endothelial decompensation. Surgery was uneventful, while the postoperative period was complicated by multiple graft detachments requiring re-bubbling. After four re-bubbling procedures, the corneal graft attached and cleared over time. RESULTS: 29 months after combined SSF IOL implant and DSAEK surgery, the patient presented with decreased vision due to IOL opacification affecting the visual axis. CONCLUSION: Although combined SSF IOL and DSAEK surgery is an overall safe and effective procedure for aphakic endothelial decompensation, risk of IOL opacification due to anterior chamber air injection is higher when using hydrophilic IOLs and in cases requiring multiple re-bubbling, therefore, intraocular lens material should be chosen after considering the risks and benefits.

Safety and Efficacy of Dexamethasone Intravitreal Implant Given Either First-Line or Second-Line in Diabetic Macular Edema.

Diabetic macular edema (DME) is a common sight-threatening complication of diabetic retinopathy (DR) and the leading cause of severe visual impairment among the working-age population. Several therapeutic options are available for the management of DME, including intravitreal corticosteroids. They have been traditionally used as second-line treatment, due to the risk of intraocular pressure increase and cataract-related adverse events. However, attention has recently been focused on the primary or early use of intravitreal corticosteroids, due to growing evidence of the crucial role of inflammation in the pathogenesis of DME. Furthermore, intravitreal steroid implants offer the additional advantage of a longer duration of action compared to anti-vascular endothelial growth factor agents (anti-VEGF). This review aims to summarize the available evidence on the efficacy and safety profile of dexamethasone (DEX) intravitreal implant, with a specific focus on clinical scenarios in which it might be considered or even preferred as first-line treatment option by adequate selection of patients, considering both advantages and possible adverse events. Patients with contraindications to anti-VEGF, DME with high inflammatory OCT biomarkers, pseudophakic patients and phakic patients' candidates to cataract surgery as well as vitrectomized eyes may all benefit from first-line DEX implant. Additionally, DME not responders to anti-VEGF should be considered for a switch to DEX implant and a combination therapy of DEX implant and anti-VEGF could be a valid option in severe and persistent DME.

Assessment of Corneal Angiography Filling Patterns in Corneal Neovascularization.

The purpose of the paper is to describe vascular filling patterns in corneal neovascularization (CoNV) and evaluate the effect of corneal lesion location, CoNV surface area and multi-quadrant CoNV involvement on the filling pattern. It is a retrospective study of patients who were investigated for CoNV using fluorescein angiography (FA) or indocyanine green angiography (ICGA) between January 2010 and July 2020. Angiography images were graded and analyzed multiple independent corneal specialists. The corneal surface was divided into four quadrants and patient information was obtained through electronic records. A total of 133 eyes were analyzed. Corneal lesions were located on the peripheral (72%) or central (28%) cornea. Central lesions were associated with multi-quadrant CoNV more frequently than peripheral lesions (p = 0.15). CoNV located within the same quadrant of the corneal lesion was often first to fill (88.4%). In multi-quadrant CoNV, the physiological inferior-superior-nasal-temporal order of filling was usually respected (61.7%). Central lesions resulted in larger CoNV surface area than peripheral lesions (p = 0.09). In multi-quadrant CoNV, the largest area of neovascularization was also the first to fill in (peripheral lesion 74%, central lesion 65%). Fillings patterns in healthy corneas have previously been reported. Despite CoNV development, these patterns are usually respected. Several factors that may influence filling patterns have been identified, including corneal lesion location, CoNV surface area and aetiology of CoNV. Understanding filling patterns of neovascularization allows for the identification of areas at higher risk of developing CoNV, aiding in earlier detection and intervention of CoNV.

Diabetic Retinopathy: Soluble and Imaging Ocular Biomarkers.

Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, represents the leading cause of acquired blindness in the working-age population. Due to the potential absence of symptoms in the early stages of the disease, the identification of clinical biomarkers can have a crucial role in the early diagnosis of DR as well as for the detection of prognostic factors. In particular, imaging techniques are fundamental tools for screening, diagnosis, classification, monitoring, treatment planning and prognostic assessment in DR. In this context, the identification of ocular and systemic biomarkers is crucial to facilitate the risk stratification of diabetic patients; moreover, reliable biomarkers could provide prognostic information on disease progression as well as assist in predicting a patient's response to therapy. In this context, this review aimed to provide an updated and comprehensive overview of the soluble and anatomical biomarkers associated with DR.

Yogurt Technique for Descemet Membrane Endothelial Keratoplasty Graft Preparation: Early Clinical Outcomes.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of the Yogurt technique for Descemet membrane endothelial keratoplasty (DMEK) graft preparation. METHODS: This study included patients who underwent DMEK combined or not with phacoemulsification surgery using donor tissues prepared by a surgeon with the DMEK Tzamalis disposable punch at 2 referral hospitals between October 2019 and June 2021. Primary outcomes were duration of graft preparation, surgeon grading of graft quality, and endothelial cell density measured at 1 and 6 months after surgery. Secondary outcomes were best-corrected visual acuity (BCVA) measured at 1 and 6 months postoperatively and DMEK intraoperative and postoperative complications. RESULTS: Forty-nine patients were included in this study. The mean DMEK graft preparation time was 7.2 ± 1.4 minutes. Donor grafts were rated good in 67.3% of cases (33 of 49), sufficient in 24.5% (12 of 49), and poor in 8.2% (4 of 49). Donor mean endothelial cell density was 2580 ± 155 preoperatively, which were reduced to 2269 ± 191 ( P < 0.000) and 1697 ± 142 ( P < 0.0001) at 1 and 6 months, respectively. No significant difference was found in graft preparation outcome ( P = 0.543). The preoperative BCVA was 0.65 ± 0.44 logMAR, which improved to 0.31 ± 0.43 logMAR ( P < 0.0001) and 0.12 ± 0.14 logMAR ( P < 0.0001) at 1 and 6 months after surgery, respectively. CONCLUSIONS: This study shows that the DMEK Tzamalis punch can be used as an effective and safe method for DMEK graft preparation with a shallow learning curve that allows it to be successfully performed by relatively inexperienced surgeons.

Artificial intelligence in cornea and ocular surface diseases.

In modern ophthalmology, the advent of artificial intelligence (AI) is gradually showing promising results. The application of complex algorithms to machine and deep learning has the potential to improve the diagnosis of various corneal and ocular surface diseases, customize the treatment, and enhance patient outcomes. Moreover, the use of AI can ameliorate the efficiency of the health-care system by providing more accurate results, reducing the workload of ophthalmologists, allowing the analysis of a big amount of data, and reducing the time and resources required for manual image acquisition and analysis. In this article, we reviewed the most important and recently published applications of AI in the field of cornea and ocular surface diseases, with a particular focus on keratoconus, infectious keratitis, corneal transplants, and the use of in vivo confocal microscopy.

Comparative performance of humans versus GPT-4.0 and GPT-3.5 in the self-assessment program of American Academy of Ophthalmology.

To compare the performance of humans, GPT-4.0 and GPT-3.5 in answering multiple-choice questions from the American Academy of Ophthalmology (AAO) Basic and Clinical Science Course (BCSC) self-assessment program, available at https://www.aao.org/education/self-assessments . In June 2023, text-based multiple-choice questions were submitted to GPT-4.0 and GPT-3.5. The AAO provides the percentage of humans who selected the correct answer, which was analyzed for comparison. All questions were classified by 10 subspecialties and 3 practice areas (diagnostics/clinics, medical treatment, surgery). Out of 1023 questions, GPT-4.0 achieved the best score (82.4%), followed by humans (75.7%) and GPT-3.5 (65.9%), with significant difference in accuracy rates (always P < 0.0001). Both GPT-4.0 and GPT-3.5 showed the worst results in surgery-related questions (74.6% and 57.0% respectively). For difficult questions (answered incorrectly by > 50% of humans), both GPT models favorably compared to humans, without reaching significancy. The word count for answers provided by GPT-4.0 was significantly lower than those produced by GPT-3.5 (160 ± 56 and 206 ± 77 respectively, P < 0.0001); however, incorrect responses were longer (P < 0.02). GPT-4.0 represented a substantial improvement over GPT-3.5, achieving better performance than humans in an AAO BCSC self-assessment test. However, ChatGPT is still limited by inconsistency across different practice areas, especially when it comes to surgery.

Recent advances in drug treatments for dry eye disease.

INTRODUCTION: Dry eye disease (DED) is a common ocular condition with a significant impact on patients' quality of life. Conventional treatments include behavioral changes, tear substitutes, and anti-inflammatory agents; however, recent advances in the understanding of DED pathogenesis have opened the way to the development of novel treatment strategies able to target several pathways involved in the onset and persistence of DED. AREAS COVERED: Literature search was conducted on PubMed and Scopus around the term 'dry eye disease' and others involving its pathophysiology and therapeutic strategy. The primary focus was on recent drugs approved by FDA or under investigation in phase 3 clinical trials. Google and ClinicalTrials.gov were used for obtaining information about the status of FDA approval and ongoing clinical trials. EXPERT OPINION: Due to its multifaced pathogenesis, DED management is often challenging, and patients' needs are frequently unmet. Recently, several novel treatments have been either FDA-approved or studied in late-phase trials. These novel drugs target-specific biological components of the ocular surface and reduce inflammation and ocular pain. Additionally, new drug delivery systems allow for increased bioavailability, improve effective dosing, and minimize ocular side effects. These advances in drug therapies show real promise for better management of DED patients.

Thinning rate over 24 months in ultrathin DSAEK.

AIM: To describe the changes in corneal graft thickness following ultrathin Descemet's Stripping Automated Endothelial Keratoplasty (UT-DSAEK) comparing pre- and postoperative values over a 24-month period. METHODS: In this retrospective single-center case series, patients who received eye bank-prepared tissues for UT-DSAEK surgery were included. Preoperative and postoperative graft thickness measurements were determined in the eye bank and in clinic using anterior segment optical coherence tomography (AS-OCT) images. Graft thickness measurements and their percentage change between preoperative values and values at 1 day, 1 week and 1, 6, 12, 24 months were calculated. RESULTS: In total, 47 eyes of 47 patients with a mean age of 69 ± 11 years (29 males) were included. Twnty-three patients had Fuchs' endothelial dystrophy (49%) and the remaining 24 had pseudophakic bullous keratopathy (51%). In total, 29/47 eyes underwent UT-DSAEK alone (62%) and 18/47 received combined cataract surgery as a triple procedure (38%). Preoperative donor graft thickness was 92 ± 28 µm. Compared to preoperative values, where graft thickness increased to 194 ± 101.3 µm at 1 day, 151.1 ± 71.4 µm at 1 week, and 108.4 ± 52.5 µm at 1 month. Graft thickness continued to gradually decrease over time until 6 months (91.7 ± 33.6 µm), and then plateaued at 12 months (83.9 ± 25.0 µm), showing minimal changes at 2 years (101.4 ± 37.5 µm). CONCLUSION: Preoperative DSAEK graft thickness measurements as reported by the eye bank are a valid approximation of DSAEK graft thickness at 6 months after surgery and these measurements tend to stabilize over time up to 2 years after surgery.