Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential.

Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.

New perspectives in keratoconus treatment: an update on iontophoresis-assisted corneal collagen crosslinking.

Keratoconus is a bilateral, asymmetric and progressive corneal disease. It usually results in apical thinning and steepening with corneal deformation and impaired vision. Since the early 1990 s, corneal collagen crosslinking (CXL) has remained the primary treatment to stabilize the progression of the disease. Iontophoresis-assisted CXL (I-CXL) has been proposed as a non-invasive alternative to standard epithelium-off technique, showing promising results. In this article, we review up to date literature to provide state of art knowledge and future perspectives of I-CXL.

Neurotrophic Keratopathy after wide retinal endolaser and postoperative Ketorolac eye drops: A case series.

PURPOSE: We report a series of 5 cases, happened in a period of 5 months, who developed neurotrophic keratopathy (NK) following pars plana vitrectomy (PPV) and retinal endolaser for rhegmatogenous retinal detachment (RRD). In our several decennary experience of surgical center predominantly based on vitreoretinal surgery, we had rare cases of postoperative NK. These recent cases of post-surgical NK happened contextually to our change of postoperative non-steroidal anti-inflammatory drugs (NSAIDs) drops, based on Ketorolac Tromethamine 0.5% eye drops. CASES PRESENTATION: Five patients with a mean age of 61 ± 7.3 years were treated with one or more PPV with intraoperative peripheral endolaser for RRD. Nobody had previous herpetic keratitis, systemic disease like diabetes mellitus or other predisposing factors for NK. In the postoperative period, all patients received Ketorolac Tromethamine 0.5% eye drops for a mean period of 54 ± 25 days. During follow-up visits they developed NK and they were successfully treated with suspension of Ketorolac eye drops, application of therapeutic contact lens or amniotic membrane patch and topical lubricant therapy. CONCLUSIONS: Postoperative Ketorolac eye drops, in patients who underwent PPV with endolaser, may reduce the corneal sensitivity, predispose to epithelial disruption and NK development. Studies are needed to explore the effect of NSAIDs on corneal sensitivity reduction in patient who will undergo PPV and extensive endolaser.

Prophylaxis of Ocular Infection in the Setting of Intraocular Surgery: Implications for Clinical Practice and Risk Management.

In this review we discuss the role of intraocular surgery preoperative prophylaxis. The correct choice of antimicrobial drug is variable in each surgical setting, according to the available strengths of evidence, the anatomical district involved, and the type of procedure. In the ophthalmic surgical field, there has been a progressive shift from antibiotic formulations, which are known to cause antibiotic resistance, to a new class of antiseptic compounds, which proved to be effective not only against bacteria, but also against fungi, protozoa, and viruses. Among these, povidone-iodine (PVI) is a water-soluble polymer that can form a complex with iodine, and the perioperative application of PVI 5-10% eye drop for 3 min is the gold standard for infection prophylaxis. A new formulation of 0.6% PVI eye drop is a new option for infection prophylaxis in the days before surgery. Chlorhexidine is a biguanide compound, which is a valid alternative with a good safety and efficacy profile and is the antiseptic of choice in patients with iodine allergy. New compounds that are currently being studied include polyhexamethylene biguanide (PHMB), picloxydine, ozone, hypochlorous acid (HOCl), and Biosecur. PHMB is a biguanide polymer that was found to be more effective than PVI in in vitro studies for reducing microorganisms and extending the duration of antisepsis, but to date, there are no formulations available on the market for preoperative ocular surgery in which it is present as main ingredient. Ozone is a molecule with oxidizing effect, which showed interesting preliminary results but is not effective against virus, Staphylococcus aureus and Candida albicans. HOCl has a natural bactericidal propriety but its applicability to prophylaxis of ocular infection in the setting of ocular surgery is not established. Biosecur is a non-toxic organic alcohol-free compound that exhibited bactericidal and fungicidal effect versus all common microorganisms and is currently available as an ocular spray.

Trans-Scleral Plugs Fixated FIL SSF IOL: A Review of the Literature and Comparison with Other Secondary IOL Implants.

Purpose. To revise the current literature on FIL SSF (Carlevale) intraocular lens, previously known as Carlevale lens, and to compare their outcomes with those from other secondary IOL implants. Methods. We performed a peer review of the literature regarding FIL SSF IOLs until April 2021 and analyzed the results only of articles with a minimum of 25 cases and a follow-up of at least 6 months. The searches yielded 36 citations, 11 of which were abstracts of meeting presentations that were not included in the analysis because of their limited data. The authors reviewed 25 abstracts and selected six articles of possible clinical relevance to review in full text. Of these, four were considered to be sufficiently clinically relevant. Particularly, we extrapolated data regarding the pre- and postoperative best corrected visual acuities (BCVA) and the complications related to the procedure. The complication rates were then compared with those from a recently published Ophthalmic Technology Assessment by the American Academy of Ophthalmology (AAO) on secondary IOL implants. Results. Four studies with a total of 333 cases were included for results analysis. The BCVA improved in all cases after surgery, as expected. Cystoid macular edema (CME) and increased intraocular pressure were the most common complications, with an incidence of up to 7.4% and 16.5%, respectively. Other IOL types from the AAO report included anterior chamber IOLs, iris fixation IOLs, sutured iris fixation IOLs, sutured scleral fixation IOLs, and sutureless scleral fixation IOLs. There was no statistically significant difference in the rates of postoperative CME (p = 0.20), and vitreous hemorrhage (p = 0.89) between other secondary implants and the FIL SSF IOL, whereas the rate of retinal detachment was significantly less with FIL SSF IOLs (p = 0.04). Conclusion. The results of our study suggest the implantation of FIL SSF IOLs is an effective and safe surgical strategy in cases where there is a lack of capsular support. In fact, their outcomes seem to be comparable to those obtained with the other available secondary IOL implants. According to published literature, the FIL SSF (Carlevale) IOL provides favorable functional results with a low rate of postoperative complications.

Camellens FIL622-1 IOL Implantation in the Ciliary Sulcus: Refractive Outcomes and Optimization of A-constant.

PURPOSE: To assess the refractive outcomes of patients who had sulcus implantation of the Camellens FIL622-1 intraocular lens (IOL) (Soleko) after posterior capsular rupture, and to optimize the A-constant suggested by the manufacturer. METHODS: This study included patients who underwent secondary Camellens FIL622-1 IOL implantation in the ciliary sulcus after complicated cataract surgery with posterior capsular rupture. IOL power was calculated by the SRK/T formula, using the recommended A-constant (118.8) for ciliary sulcus implantation. A new optimized A-constant was obtained and used to evaluate the refractive outcomes. The main outcome measures were mean prediction error (PE), median absolute error (MedAE), mean absolute error (MAE), and percentage of eyes with a PE within ±0.50, ±1.00, and ±2.00 diopters (D). RESULTS: Forty patients (40 eyes) were included in the study. The new optimized A-constant was 117.5, and the mean PE, MedAE, and MAE was -0.02 ± 0.73, 0.34, and 0.54, respectively. The percentage of eyes with a PE within ±0.50, ±1.00, and ±2.00 D was 65%, 87.5%, and 100%, respectively. CONCLUSIONS: The Camellens FIL622-1 IOL represents a valid option as sulcus implantation after posterior capsular rupture and it would guarantee the surgeon an on-label option with a more accurate biometric calculation, at the time of surgical implantation, with the new optimized A-constant. [J Refract Surg. 2022;38(12):806-811.].

Corneal Cross-linking for Progressive Keratoconus in Patients Older Than 40 Years: Long-term Follow-up.

PURPOSE: To assess the long-term efficacy and safety of epithelium-off corneal cross-linking according to the standard (Dresden) protocol (S-CXL) in patients with progressive keratoconus older than 40 years. METHODS: Seventy-six eyes of 64 patients with a mean age of 46.4 ± 5.2 years were included. At baseline and after 6, 12, 24, 36, 48, 60, 72, 84, and more than 96 months (when available) after S-CXL, all patients were assessed with distance-corrected visual acuity (DCVA) and corneal topography and tomography with Pentacam HR (OCULUS Optikgeräte GmbH). A generalized linear model was used to compare the groups. Outcome measures were maximum keratometry, thinnest point, coma, spherical, and higher order aberrations, and ABC values. Fixed and random factors were age, gender, atopy, laterality, and group. RESULTS: The mean follow-up time was 62.1 ± 40.1 months (range: 12 to 144 months). The main outcome of the study was the evidence that S-CXL was able to safely stop the progression of keratoconus in all patients with none requiring repeat CXL. The generalized linear model analysis showed no significant change in DCVA over time (P = 1.000), but atopy was negatively associated with DCVA (P = .030, B = -0.69). The generalized linear model also showed that CXL was able to induce a significant flattening demonstrated as reduction of maximum keratometry (P = .001, B = -0.35) and A value (P =.001, B = -0.015) of the ABC display. Similarly, coma aberration was reduced over time (P = .006, B = -0.005). CONCLUSIONS: S-CXL was confirmed to be a safe and effective treatment for progressive keratoconus even after the age of 40 years, inducing a significant flattening of the cone. [J Refract Surg. 2021;37(5):338-342.].

Outcomes of Abrupt Switch to Bevacizumab of Patients Undergoing Aflibercept Intravitreal Injections for Neovascular Age-Related Macular Degeneration in a Tertiary Center in Lombardy, Italy: A Real-Life Retrospective Analysis.

PURPOSE: To assess real-life anatomical and functional outcomes of switch to bevacizumab in patients undergoing aflibercept intravitreal injections for nAMD. METHODS: Retrospective chart review of all patients diagnosed with nAMD and undergoing intravitreal injections of aflibercept who switched to bevacizumab after the resolution XI/1986 of Lombardy Region. RESULTS: Among 128 patients undergoing intravitreal injections, a total of 29 eyes of 29 patients met all inclusion criteria and were included in the statistical analysis. Best corrected visual acuity and central macular thickness did not change significantly (p > 0.05) between baseline, after the loading phase, and at the last follow-up. CONCLUSION: Switching to bevacizumab has been safe and efficacious in patients responding to the loading phase. According to our results, the restrictions imposed by Lombardy Region did not cause any harm to patients undergoing intravitreal anti-VEGF injections.

Management of an ophthalmology department during COVID-19 pandemic in Milan, Italy.

PURPOSE: Spreading from China, COVID-19 pandemic reached Italy, the first massively involved western nation. At the beginning of March, 2020 in Northern Italy a complete lockdown of activities was imposed. Access to all healthcare providers, was halted for patients with elective problems. We present the management experience of the Humanitas Clinical and Research Center Ophthalmology Department in Rozzano, Milan, Italy, during the lockdown. METHODS: Containment measures were taken to reduce viral transmission and identify infected patients. All planned visits were canceled but for those not deferrable. Social distancing was introduced reducing number of visits per hour. Minor surgery for progressive pathologies was continued. As the lockdown prolonged, we reorganized patient care. All canceled cases were evaluated by electronic medical records analysis and telephonic triage, to identify, recall, and visit patients at risk of vision loss. RESULTS: From March 9, to April 30, 2020 we performed a total of 930 visits and 612 exams. Some visits (n = 698) and exams (n = 160) were deemed as necessary for continuity of care and performed as planned. Among the remaining 1283 canceled appointments, after evaluation 144 visits and 32 instrumental exams were classified as urgent and rapidly rescheduled. Performed surgical activities were limited to corneal collagen cross linking (n = 39) and intravitreal injections (n = 91), compared to 34 and 94, respectively, in the same period of 2019. CONCLUSION: In-office activities deemed not deferrable were performed safely. The recall service was highly appreciated by all patients. No patient or staff member reported symptoms of COVID-19.

Characterization of the folding landscape of monomeric lactose repressor: quantitative comparison of theory and experiment.

Recent theoretical/computational studies based on simplified protein models and experimental investigation have suggested that the native structure of a protein plays a primary role in determining the folding rate and mechanism of relatively small single-domain proteins. Here, we extend the study of the relationship between protein topology and folding mechanism to a larger protein with complex topology, by analyzing the folding process of monomeric lactose repressor (MLAc) computationally by using a Go-like C(alpha) model. Next, we combine simulation and experimental results (see companion article in this issue) to achieve a comprehensive assessment of the folding landscape of this protein. Remarkably, simulated kinetic and equilibrium analyses show an excellent quantitative agreement with the experimental folding data of this study. The results of this comparison show that a simplified, completely unfrustrated C(alpha) model correctly reproduces the complex folding features of a large multidomain protein with complex topology. The success of this effort underlines the importance of synergistic experimental/theoretical approaches to achieve a broader understanding of the folding landscape.