MRI and Clinical Biomarkers Overlap between Glaucoma and Alzheimer's Disease.

Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber layer, but the damage is not limited to the eye. The involvement of the central visual pathways and disruption of brain network organization have been reported using advanced neuroimaging techniques. The brain structural changes at the level of the areas implied in processing visual information could justify the discrepancy between signs and symptoms and underlie the analogy of this disease with neurodegenerative dementias, such as Alzheimer's disease, and with the complex group of pathologies commonly referred to as "disconnection syndromes." This review aims to summarize the current state of the art on the use of advanced neuroimaging techniques in glaucoma and Alzheimer's disease, highlighting the emerging biomarkers shared by both diseases.

Corneal transplant during COVID-19 pandemic: the Italian Eye Bank national report.

To investigate the impact of Coronavirus Disease-2019 lockdown on the Italian Eye Bank organization. In this national retrospective, multicentric, cohort study, data from the Italian Eye Bank during both the lockdown and the first month after the lockdown period were retrieved. We compared the Italian Eye Bank metrics with the same timeframe of 2019 and 2018. Data from 13 out of 13 (100%) Italian Eye Banks were included in the analysis. A statistically significant reduction in the number of donor corneas retrieved in 2020 was found as compared to the same period in 2019 and in 2018, respectively (2020 = 1284; 2019 = 3088; 2018 = 3221; ANOVA: p < 0.0001). Only 534 corneas have been distributed by Eye Banks during the COVID-19-lockdown period (2020 = 534; 2019 = 1220; 2018 = 1237. ANOVA: p < 0.0001). Similarly, the number of wasted corneas due to postponed or cancelled surgeries was 421, resulting in a considerable increase as compared to the previous 2 years (2020 = 421; 2019 = 67; 2018 = 84; ANOVA: p = 0.0035). Overall, 45 donor corneas were rejected in accordance with the guidance of the Italian National Health Institute Italian National Transplant Centre (CNT). SARS-CoV-2 pandemic has profoundly affected every social and medical field, including the Eye Bank procurement and distribution programs. The current data collected from all the Italian Eye Banks highlights the present and the forthcoming difficulties that the Eye Bank community is going to experience, as for the ongoing pandemic.

Clinical Outcomes of Modified Manual Deep Anterior Lamellar Keratoplasty for Eyes with Previous Radial Keratotomy.

Background: The aim of this study was to evaluate the intraoperative complications and visual outcomes of manual deep anterior lamellar keratoplasty (mDALK) in patients who underwent previous radial keratotomy (RK) for myopia. Methods: The notes of patients who underwent mDALK after RK at three different hospitals-San Giovanni Addolorata Hospital (Rome, Italy), Mount Saint Joseph Hospital (Vancouver, Canada), and Tor Vergata University Hospital (Rome, Italy)-were retrospectively reviewed. We analyzed the manual dissection success rate and conversion to penetrating keratoplasty (PK), the residual recipient stromal thickness, the postoperative corrected distance visual acuity (CDVA), postoperative refraction, and topographic astigmatism. Results: Thirteen eyes of eleven patients were included in the analysis (male 7/11, 63.6%). Preoperatively, mean topographic astigmatism was 5.4 ± 3.5 D (range 1.6-14.8 D), and mean CDVA was 0.47 ± 0.2 logMAR (range 0.3-1.0 logMAR) [Snellen equivalent 20/50]. Manual dissection was performed in all cases. None of the examined eyes were converted to PK. An improvement in both topographic astigmatism (2.8 ± 0.9 D, p = 0.0135) and CDVA (0.23 ± 0.2 LogMAR, p = 0.0122) was recorded at 12-month follow-up. Conclusions: mDALK is a safe and effective surgical technique when applied to eyes previously treated with RK, with an observed improvement in CDVA and topographic astigmatism.

Incidence and outcomes of post-operative endophthalmitis following elective phacoemulsification cataract surgery, between 2015 and 2022.

BACKGROUND: Cataract surgery remains the commonest ophthalmic surgical procedure in the UK. Post-operative endophthalmitis (POE) is a sight-threatening complication. This study presents the incidence and outcomes of POE within Moorfields Eye Hospital NHS Foundation Trust (MEH) in London, UK. METHODS: We conducted a retrospective, tertiary-centre study of the incidence and outcomes of POE following elective phacoemulsification cataract surgery between 2015 and 2022. RESULTS: We report a rate of 18 out of 154 826 (0.012%) cases of POE within seven weeks of cataract surgery. The age range was 43-87 years (mean age 67.1 years), and the male-to-female ratio was 1:1. Two cases were associated with intraoperative vitreous loss, one with anterior capsular tear extending to posterior capsular tear and the other with posterior capsular tear and dropped fragment. Two cases had a concomitant intravitreal injection, one of Triamcinolone Acetonide and the other of Dexamethasone implant (Ozurdex®), to manage chronic uveitic macular oedema. The majority of samples (89.9%) resulted in Gram-positive species. A final best corrected visual acuity (BCVA) of Snellen 6/36 or better was achieved in 12/18 (66.67%). The time from cataract surgery to suspicion of POE ranged from 3 to 44 days (mean 15.8 days). Eight cases (44.4%) required pars plana vitrectomy (PPV). CONCLUSIONS: We demonstrate an incidence of POE of 0.012% following phacoemulsification at MEH from January 2015 to December 2022. Such results are a testament to high-quality surgery, training supervision and post-operative care whilst adhering to local and international standards.

Keratoconus and Personality Traits: A Case-Control Study.

PURPOSE: The aim of this study was to delineate the personality traits of patients affected by keratoconus (KC) compared with a group of nonkeratoconic controls matched in age and sex. METHODS: In this prospective interventional case-control study, 60 consecutive subjects (30 KC cases and 30 healthy controls), aged 18 to 30, were enrolled at the time of their first encounter at the ophthalmology unit of the Fondazione Policlinico "Tor Vergata", Roma. After completing the ophthalmic evaluation, participants were asked to respond to the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). A complete psychiatric assessment was performed, including the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (SCID-5); the Symptom Check List-90-Revised (SCL-90); the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Modified (TEMPS-M); and the NEO Five-Factor Inventory (NEO-FFI). RESULTS: Cases had lower quality of life than controls, as demonstrated by lower scores in all NEI VFQ-25 subdomains. Nine patients with KC (30.0%) were diagnosed by the SCID-5 with at least 1 cluster C personality disorder, resulting in a 9-fold increased risk compared with controls. Moreover, keratoconic patients showed a more pronounced psychosomatic symptomatology (SCL-90) and a characteristic neurotic temperament (TEMPS-M and NEO-FFI). CONCLUSIONS: Our results support the hypothesis that subjects with KC feature dysfunctional coping mechanisms and personality traits, which might already be present at the first clinical encounter. Ophthalmologists should question the mental and emotional status of patients with KC and be especially careful in managing these patients.

Influence of Opacity Depth on Big Bubble Formation During Deep Anterior Lamellar Keratoplasty in Corneal Stromal Scars.

PURPOSE: To identify the key preoperative predictors of big bubble (BB) formation during deep anterior lamellar keratoplasty in patients with corneal stromal scars (CSS). METHODS: This retrospective cohort study included consecutive patients with CSS after infective keratitis who underwent BB-deep anterior lamellar keratoplasty between January 2021 and July 2023 at a tertiary referral center. Topographic and tomographic data were collected to compare the rates and types of BB formations. Anterior segment optical coherence tomography (AS-OCT) was employed to assess the maximum depth of opacity by dividing the stroma into 3 zones of equal thickness: anterior (stage A), mid (stage B), and posterior stroma (stage C). Multivariate logistic regression analysis was performed to identify the potential preoperative predictors of bubble formation. RESULTS: Pneumatic dissection was achieved in 13 of 33 eyes (39.4%), with 11 BB type 1 eyes (33.3%) and 2 BB type 2 eyes (6.1%). According to AS-OCT grading, bubble formation was more frequent with CSS involving more superficial stromal layers (P <0.032). In the eyes with stage C, bubble formation failed 12 out of 14 times (85.7%, P <0.026). Spearman correlation showed that bubble formation was inversely associated with the AS-OCT grading (rho = -0.443, P = 0.001). After logistic regression analysis, AS-OCT grading was found to be the sole factor that predicted bubble formation (coeff. -1.58, confidence interval 95% -3.03 to -0.12, P = 0.034). CONCLUSIONS: Depth of opacity in CSS was the key determinant for predicting the success of pneumatic dissection, as advanced AS-OCT stages are strongly associated with BB failure.

Tomographic and topographic predictive factors of big bubble formation during deep anterior lamellar keratoplasty in keratoconus.

PURPOSE: To identify preoperative predictors of big bubble (BB) formation during deep anterior lamellar keratoplasty (DALK) in patients with keratoconus (KC). METHODS: DESIGN: Retrospective cohort study in an Italian tertiary centre. STUDY POPULATION: Consecutive patients with KC undergoing DALK from January 2021 to July 2023. OBSERVATION PROCEDURE: Tomographic and topographic data including K-max, K-mean, keratometric astigmatism, thinnest point, mean peripheral corneal thickness, difference between the mean peripheral corneal thickness and the thinnest point (peripheral-minimal corneal thickness), position (central/paracentral) and cone area (%), Amsler-Krumeich classification and anterior segment optical coherence tomography (AS-OCT) analysis to assess the severity stage. MAIN OUTCOME MEASURES: Rate of BB formation and type; multivariate logistic regression analysis was used to analyse all preoperative parameters in patients with BB formation versus failure. RESULTS: Pneumatic dissection succeeded in 98 of 140 eyes (70.0%), with 94 type 1 bubbles (67.1%) and four type 2 bubbles (2.9%). BB formation succeeded more frequently in patients with lower K-max (p=0.032), lower K-mean (p=0.010), higher thinnest point (p=0.017), lower peripheral-minimal corneal thickness (p=0.009) and lower Amsler-Krumeich stages (p=0.021). According to the AS-OCT analysis, BB formation was more frequent in the lower stages (p<0.001). After the logistic regression (pseudo-R²=0.176, constant=3.21, 95% CI 1.14 to 5.29, p=0.002), AS-OCT classification was found to be the only factor that predicted BB formation (coefficient=-0.81, 95% CI -1.18 to -0.43, p<0.001). CONCLUSIONS: AS-OCT classification is a reliable predictor for BB formation. Tomographic and topographic analyses indicated that a steeper and more ectatic cornea is more prone to BB failure.

Effect of genotype on individual response to the pharmacological treatment of glaucoma: a systematic review and meta-analysis.

The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.

Effect of Covid-19 on Eye Banks and Corneal Transplantations: Current Perspectives.

The coronavirus disease 2019 (COVID-19) pandemic exerted a great impact on medical practice, which was reframed according to the actual needs. Ophthalmological services and procedures including corneal transplantation did not represent an exception. The adoption and implementation of new standard operating procedures as well as of new technologies for remote consultation and smart-working reshaped daily activities of both eye bankers, physicians, researchers, and patients. Regulatory restrictions were issued redefining corneal donor eligibility criteria, as well as handling and harvesting procedures of donor ocular tissues. Surgical schedules underwent an abrupt contraction with prioritization of urgent procedures. Local lockdowns and confinement strategies resulted in both a reduction and redirection of research activities. The evaluation of SARS-CoV-2 colonization of ocular tissues, long-term corneal storage techniques, new disinfection strategies, split corneal transplants and cell-based therapies for the treatment of corneal disease peaked in the pipeline. Aim of this article is to summarizes the overall impact of the pandemic on the corneal transplantation machinery, and the current and future perspectives for the corneal transplant community.

Impact of the COVID-19 Pandemic on Corneal Transplantation: A Report From the Italian Association of Eye Banks.

Purpose: To analyze the impact of COVID-19 on Italian corneal transplantation from March-2020 to February 2021 compared to the same timeframe of the 2 previous years, in order to identify potential consequences of a global pandemic on corneal procurement and transplantation services during this time. Methods: This national, multicentric, retrospective cohort study evaluated data collected from 12 (100%) Italian eye banks from March 2020 to February 2021 (Group A). The number of tissues collected, distributed and discarded were compared with the same time-frame of the 2 previous years: 2019 and 2018 (group B and C, respectively). The different type of transplants performed were reported. Data were analyzed using a non-parametric Friedman test. Results: Corneal procurement and the percentage of distributed tissues reduced in 2020 by more than 30 and 15%, respectively, compared to the 2 previous years. During the pandemic corneal transplant surgery showed only a modest drop: the number of the penetrating keratoplasties (PKs) and the anterior lamellar keratoplasties (ALKs) decreased by about 30 and 20% in comparison with groups B and C, respectively; between the Endothelial Keratoplasties (EKs), the Descemet membrane endothelial keratoplasty (DMEK) increased slightly from March 2020 to February 2021. Conclusions: Italy was one of the first countries most affected by the outbreak of COVID-19, and the Italian government adopted severe measures to limit viral transmission. The pandemic generated several implications in corneal transplant activity during the first lockdown. Then an efficacious reaction with constant, vigorous work led to a resumption of transplant surgery to a near-normal standard. The increase of EKs, despite the pandemic, is a sign that the advance in corneal transplantation has gone ahead and it continues to evolve.

Imaging biomarkers for Alzheimer's disease and glaucoma: Current and future practices.

Glaucoma is a leading cause of blindness worldwide. Although intraocular pressure is the main risk factor for glaucoma, several intraocular pressure independent factors have been associated with the risk of developing the disease and its progression. The diagnosis of glaucoma relies on clinical features of the optic nerve, visual field test, and optical coherence tomography. However, the multidisciplinary aspect of the disease suggests that other biomarkers may be useful for the diagnosis, thus underling the importance of novel imaging techniques supporting clinicians. This review analyzes the common pathogenic mechanisms between glaucoma and Alzheimer's disease and the possible novel approaches for diagnosis and follow up.

Role of Topical Cenegermin in Management of a Cornea Transplant in a Functionally Monocular Patient with Neurotrophic Keratitis and Facial Nerve Palsy: A Case Report.

BACKGROUND: NK is one of the most challenging ocular conditions to treat and it can represent a devastating complication of acoustic neuroma surgery due to the profound corneal anesthesia and concomitant exposure keratopathy caused by seventh nerve palsy. In such cases, cornea surgery should be considered with extreme caution due to the high risk of devastating complications. The purpose of the study is to report the efficacy of a novel human recombinant nerve growth factor (rhNGF)-based ophthalmic treatment in a functionally monocular patient with a recurrence of severe neurotrophic keratitis (NK) on a corneal graft. CASE PRESENTATION: A 24-year-old woman who underwent acoustic neuroma surgery was referred for the assessment of a lagophthalmos and a paracentral corneal ulcer refractory to medical treatment. The patient presented with a large descemetocele, diagnosed as stage 3 NK that required multilayer amniotic membrane transplantation (AMT) and a following optical penetrating keratoplasty (PK). The recurrence of NK on the graft was successfully treated with a cycle of rhNGF (cenegermin 20 µg/mL) eye drops. Due to the complications of a further NK recurrence after treatment discontinuation, a second AMT and PK approach was chosen. A second cycle of treatment with cenegermin was immediately initiated after PK to prevent further recurrences. No postoperative complications were observed and we report a stable situation at 1 year of follow-up. CONCLUSION: The case presented here is, to our knowledge, the first report of a treatment with cenegermin for a NK recurrence after PK and suggests that such early medical approach could be evaluated to prevent postoperative complications.

Links between obstructive sleep apnea and glaucoma neurodegeneration.

In the last few years, the possible link between obstructive sleep apnea (OSAS) and glaucoma, has attracted the interest of many scientists, especially in those forms of primary open angle glaucoma (POAG) and normal tension glaucoma (NTG), in which a progression of the disease occurs, even though intraocular pressure (IOP) is in the range of normality. The increased prevalence of POAG or NTG in patients affected by OSAS, and vice versa, has stimulated interest in the pathogenetic mechanisms that could trigger these two diseases. Hypoxia generated by apnea/hypopnea cycles has been identified as the main cause of many changes in the vascular and neurological systems, which alter the functioning not only of the optic nerve, but also of the whole organism. However, many other factors could be involved, like mechanical factors, obesity, hormonal imbalance and other sleep disorders. Furthermore, the demonstration of typical glaucomatous or glaucoma-like changes in the anatomy or function of the optic nerve and retinal nerve fiber layer by sensitive specific and diagnostic methods, such as perimetry, optical coherence tomography (OCT), optical coherence tomography angiography (OCTA) and electrophysiological exams keeps interest high for this field of study. For this reason, further investigations, hopefully a source of stronger scientific evidences, are needed.

Cataract surgery with intraocular lens implantation in 3 brothers with megalocornea: Long-term follow-up.

Cataract surgery in patients with megalocornea is challenging because of the large capsular bag in which a conventional intraocular lens (IOL) does not fit and the atrophic nature of the iris. We report the procedures and outcomes of cataract surgery in 6 eyes of 3 brothers with megalocornea. In 2 eyes, a posterior chamber IOL (PC IOL) was inserted and sutured to the iris with 10-0 nylon sutures. In the other 4 eyes, an iris-clip anterior chamber IOL (AC IOL) was inserted. In all cases, the postoperative corrected distance visual acuity (CDVA) was 6/6. In the PC IOL group, 1 IOL dislocated and was replaced with an iris-clip AC IOL. In the AC IOL group, 1 IOL subluxated and was reenclavated. In both eyes with dislocation, the CDVA improved to 6/6.

Spectral Domain Optical Coherence Tomography Assessment of Macular and Optic Nerve Alterations in Patients with Glaucoma and Correlation with Visual Field Index.

INTRODUCTION: To evaluate the sectorial thickness of single retinal layers and optic nerve using spectral domain optic coherence tomography (SD-OCT) and highlight the parameters with the best diagnostic accuracy in distinguishing between normal and glaucoma subjects at different stages of the disease. MATERIAL AND METHODS: For this cross-sectional study, 25 glaucomatous (49 eyes) and 18 age-matched healthy subjects (35 eyes) underwent a complete ophthalmologic examination including visual field testing. Sectorial thickness values of each retinal layer and of the optic nerve were measured using SD-OCT Glaucoma Module Premium Edition (GMPE) software. Each parameter was compared between the groups, and the layers and sectors with the best area under the receiver operating characteristic curve (AUC) were identified. Correlation of visual field index with the most relevant structural parameters was also evaluated. RESULTS AND DISCUSSION: All subjects were grouped according to stage as follows: Controls (CTRL); Early Stage Group (EG) (Stage 1 + Stage 2); Advanced Stage Group (AG) (Stage 3 + Stage 4 + Stage 5). mGCL TI, mGCL TO, mIPL TO, mean mGCL, cpRNFLt NS, and cpRNFLt TI showed the best results in terms of AUC according classification proposed by Swets (0.9 < AUC < 1.0). These parameters also showed significantly different values among group when CTRL vs EG, CTRL vs AG, and EG vs AG were compared. SD-OCT examination showed significant sectorial thickness differences in most of the macular layers when glaucomatous patients at different stages of the disease were compared each other and to the controls.