Herpes simplex keratitis: A brief clinical overview.

The aim of our minireview is to provide a brief overview of the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type of corneal viral infection is caused by the herpes simplex virus (HSV), which can affect several tissues, including the cornea. One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea. After the initial infection, the HSV can establish a latent infection in the trigeminal ganglion, a nerve cluster near the eye. The virus may remain dormant for extended periods. Periodic reactivation of the virus can occur, leading to recurrent episodes of HSK. Factors triggering reactivation include stress, illness, immunosuppression, or trauma. Recurrent episodes can manifest in different clinical patterns, ranging from mild epithelial involvement to more severe stromal or endothelial disease. The severity and frequency of recurrences vary among individuals. Severe cases of HSK, especially those involving the stroma and leading to scarring, can result in vision impairment or even blindness in extreme cases. The cornea's clarity is crucial for good vision, and scarring can compromise this, potentially leading to visual impairment. The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization. Antiviral medications, such as oral Acyclovir or topical Ganciclovir, may be prescribed for prophylaxis. The immune response to the virus can contribute to corneal damage. Inflammation, caused by the body's attempt to control the infection, may inadvertently harm the corneal tissues. Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation. In summary, the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

Artificial Intelligence (AI) for Early Diagnosis of Retinal Diseases.

Artificial intelligence (AI) has emerged as a transformative tool in the field of ophthalmology, revolutionizing disease diagnosis and management. This paper provides a comprehensive overview of AI applications in various retinal diseases, highlighting its potential to enhance screening efficiency, facilitate early diagnosis, and improve patient outcomes. Herein, we elucidate the fundamental concepts of AI, including machine learning (ML) and deep learning (DL), and their application in ophthalmology, underscoring the significance of AI-driven solutions in addressing the complexity and variability of retinal diseases. Furthermore, we delve into the specific applications of AI in retinal diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), Macular Neovascularization, retinopathy of prematurity (ROP), retinal vein occlusion (RVO), hypertensive retinopathy (HR), Retinitis Pigmentosa, Stargardt disease, best vitelliform macular dystrophy, and sickle cell retinopathy. We focus on the current landscape of AI technologies, including various AI models, their performance metrics, and clinical implications. Furthermore, we aim to address challenges and pitfalls associated with the integration of AI in clinical practice, including the "black box phenomenon", biases in data representation, and limitations in comprehensive patient assessment. In conclusion, this review emphasizes the collaborative role of AI alongside healthcare professionals, advocating for a synergistic approach to healthcare delivery. It highlights the importance of leveraging AI to augment, rather than replace, human expertise, thereby maximizing its potential to revolutionize healthcare delivery, mitigate healthcare disparities, and improve patient outcomes in the evolving landscape of medicine.

The Treatment of Diabetic Retinal Edema with Intravitreal Steroids: How and When.

Diabetic macular edema (DME) is a common complication of diabetes mellitus and a leading cause of visual impairment worldwide. It is defined as the diabetes-related accumulation of fluid, proteins, and lipids, with retinal thickening, within the macular area. DME affects a significant proportion of individuals with diabetes, with the prevalence increasing with disease duration and severity. It is estimated that approximately 25-30% of diabetic patients will develop DME during their lifetime. Poor glycemic control, hypertension, hyperlipidemia, diabetes duration, and genetic predisposition are recognized as risk factors for the development and progression of DME. Although the exact pathophysiology is still not completely understood, it has been demonstrated that chronic hyperglycemia triggers a cascade of biochemical processes, including increased oxidative stress, inflammation, activation of vascular endothelial growth factor (VEGF), cellular dysfunction, and apoptosis, with breakdown of the blood-retinal barriers and fluid accumulation within the macular area. Early diagnosis and appropriate management of DME are crucial for improving visual outcomes. Although the control of systemic risk factors still remains the most important strategy in DME treatment, intravitreal pharmacotherapy with anti-VEGF molecules or steroids is currently considered the first-line approach in DME patients, whereas macular laser photocoagulation and pars plana vitrectomy may be useful in selected cases. Available intravitreal steroids, including triamcinolone acetonide injections and dexamethasone and fluocinolone acetonide implants, exert their therapeutic effect by reducing inflammation, inhibiting VEGF expression, stabilizing the blood-retinal barrier and thus reducing vascular permeability. They have been demonstrated to be effective in reducing macular edema and improving visual outcomes in DME patients but are associated with a high risk of intraocular pressure elevation and cataract development, so their use requires an accurate patient selection. This manuscript aims to provide a comprehensive overview of the pathology, epidemiology, risk factors, physiopathology, clinical features, treatment mechanisms of actions, treatment options, prognosis, and ongoing clinical studies related to the treatment of DME, with particular consideration of intravitreal steroids therapy.

The Role of Human Pluripotent Stem Cells in Amyotrophic Lateral Sclerosis: From Biological Mechanism to Practical Implications.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of both upper and lower motor neurons, resulting in clinical features such as muscle weakness, paralysis, and ultimately, respiratory failure. Nowadays, there is not effective treatment to reverse the progression of the disease, that leads to death within 3-5 years after the onset. Nevertheless, the induced pluripotent stem cells (iPS) technology could be the answer, providing disease modelling, drug testing, and cell-based therapies for this pathology. The aim of this work was to conduct a literature review of the past 5 years about the role of iPS in ALS, to better define the neurobiological mechanisms involved in the pathogenesis and the potential future therapies. The review also deals with advanced and currently available technologies used to reprogram cell lines and generate human motor neurons in vitro, which represent the source to study the pathological processes, the relationship between phenotype and genotype, the disease progression and the potential therapeutic targets of these group of disorders. Specific treatment options with stem cells involve Advance Gene Editing Technology, neuroprotective agents, and cells or exosomes transplantation, aimed to replace dead or damaged nerve cells. In summary, this review comprehensively addresses the role of human pluripotent stem cells (hPSCs) in motor neuron diseases (MND), with a focus on physiopathology, diagnostic and prognostic implications, specific and potential future treatment options. Understanding the biological mechanisms and practical implications of hPSCs in MND is crucial for advancing therapeutic strategies and improving outcomes for patients affected by these devastating diseases.

Unlocking the versatile potential: Adipose-derived mesenchymal stem cells in ocular surface reconstruction and oculoplastics.

This review comprehensively explores the versatile potential of mesenchymal stem cells (MSCs) with a specific focus on adipose-derived MSCs. Ophthalmic and oculoplastic surgery, encompassing diverse procedures for ocular and periocular enhancement, demands advanced solutions for tissue restoration, functional and aesthetic refinement, and aging. Investigating immunomodulatory, regenerative, and healing capacities of MSCs, this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside, addressing common unmet needs in the field of reconstructive and regenerative surgery.

Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.

Glaucoma, a complex and multifactorial neurodegenerative disorder, is a leading cause of irreversible blindness worldwide. Despite significant advancements in our understanding of its pathogenesis and management, early diagnosis and effective treatment of glaucoma remain major clinical challenges. Epigenetic modifications, encompassing deoxyribonucleic acid (DNA) methylation, histone modifications, and non-coding RNAs, have emerged as critical regulators of gene expression and cellular processes. The aim of this comprehensive review focuses on the emerging field of epigenetics and its role in understanding the complex genetic and molecular mechanisms underlying glaucoma. The review will provide an overview of the pathophysiology of glaucoma, emphasizing the intricacies of intraocular pressure regulation, retinal ganglion cell dysfunction, and optic nerve damage. It explores how epigenetic modifications, such as DNA methylation and histone modifications, can influence gene expression, and how these mechanisms are implicated in glaucomatous neurodegeneration and contribute to glaucoma pathogenesis. The manuscript discusses evidence from both animal models and human studies, providing insights into the epigenetic alterations associated with glaucoma onset and progression. Additionally, it discusses the potential of using epigenetic modifications as diagnostic biomarkers and therapeutic targets for more personalized and targeted glaucoma treatment.

Unveiling Ocular Manifestations in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder characterized by immune dysregulation and multi-organ involvement. In this concise brief review, we highlight key insights into Ocular Systemic Lupus Erythematosus (SLE), an intricate autoimmune disorder with diverse organ involvement. Emphasizing the formation of autoantibodies and immune complex deposition, we delve into the inflammation and damage affecting ocular structures. Clinical presentations, ranging from mild dry eye syndrome to severe conditions like retinal vasculitis, necessitate a comprehensive diagnostic approach, including clinical exams, serological testing, and imaging studies. Differential diagnosis involves distinguishing SLE-related ocular manifestations from other autoimmune and non-inflammatory ocular conditions. The multidisciplinary management approach, involving rheumatologists, ophthalmologists, and immunologists, tailors treatment based on ocular involvement severity, encompassing corticosteroids, immunosuppressive agents, and biologics. Follow-up is crucial for monitoring disease progression and treatment response. Future perspectives revolve around advancing molecular understanding, refining diagnostic tools, and exploring targeted therapies. Novel research areas include genetic factors, microbiome composition, and biotechnology for tailored and effective SLE ocular treatments.

Descemetic Deep Anterior Lamellar Keratoplasty versus Penetrating Keratoplasty in Advanced Keratoconus: Comparison of Visual and Refractive Outcomes.

Purpose: To assess and contrast the visual and refractive results of Descemetic deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) in the treatment of advanced keratoconus. Design: Retrospective, comparative, interventional study. Methods: This study enrolled eyes affected by keratoconus with preoperative mean keratometry ≥60 diopters (D) that were treated with either Descemetic DALK (30 eyes) or PK (29 eyes) by using always the same corneal diameters (8.00mm recipient; 8.25mm donor cornea) and the same suture technique (10-0 nylon double-running 12-bites continuous suture). The outcome measures were postoperative uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (CDVA), subjective refractive astigmatism (SRAst), and keratometric astigmatism at 3mm area (SimK), spherical equivalent (SEq). Results: Postoperative visual acuity significantly improved in both groups. Mean CDVA was higher in the DALK group 3 months (DALK 0.61, PK 0.42, p<0.05), 6 months (DALK 0.69, PK 0.44, p<0.05), and 12 months (DALK 0.72, PK 0.45, p<0.05) postoperatively. However, 6 months after suture removal, CDVA was not statistically different between the two groups (DALK 0.71, PK 0.75, p>0.05). Final SRAst and SimK also were comparable between the two groups (respectively DALK 2.97, PK:2.81, p>0.05; DALK 3.91, PK 2.37, p>0.05). No significant statistical differences were noted for UCVA and SEq data during the entire follow-up period between the two groups. Conclusion: Both methods of corneal transplantation resulted in a notable enhancement of visual and refractive outcomes in eyes afflicted by advanced keratoconus. Descemetic DALK demonstrated superior visual acuity before suture removal, whereas DALK and PK exhibited comparable results in terms of visual acuity, refractive correction, and keratometric astigmatism after suture removal.

Uveal melanoma: Recent advances in immunotherapy.

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established. The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM's distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11. As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

From Bedside to Diagnosis: The Role of Ocular Fundus in Systemic Infections.

In this comprehensive review, we delve into the significance of the ocular fundus examination in diagnosing and managing systemic infections at the bedside. While the utilization of advanced ophthalmological diagnostic technologies can present challenges in bedside care, especially for hospitalized patients confined to their beds or during infection outbreaks, the ocular fundus examination often emerges as an essential, and sometimes the only practical, diagnostic tool. Recent discussions have highlighted that the role of an ocular fundus examination might not always be advocated as a routine diagnostic procedure. With this context, we introduce a decision tree tailored for assessing the ocular fundus in inpatients with systemic infections. We also present an overview of systemic infections that impact the eye and elucidate key signs detectable through a bedside ocular fundus examination. Targeted primarily at non-ophthalmology clinicians, this review seeks to offer a comprehensive insight into a multifaceted approach and the enhancement of patient clinical outcomes.

Recent Developments in Gene Therapy for Neovascular Age-Related Macular Degeneration: A Review.

Age-related macular degeneration (AMD) is a complex and multifactorial disease and a leading cause of irreversible blindness in the elderly population. The anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management and prognosis of neovascular AMD (nAMD) and is currently the standard of care for this disease. However, patients are required to receive repeated injections, imposing substantial social and economic burdens. The implementation of gene therapy methods to achieve sustained delivery of various therapeutic proteins holds the promise of a single treatment that could ameliorate the treatment challenges associated with chronic intravitreal therapy, and potentially improve visual outcomes. Several early-phase trials are currently underway, evaluating the safety and efficacy of gene therapy for nAMD; however, areas of controversy persist, including the therapeutic target, route of administration, and potential safety issues. In this review, we assess the evolution of gene therapy for nAMD and summarize several preclinical and early-stage clinical trials, exploring challenges and future directions.

Optical Coherence Tomography (OCT): A Brief Look at the Uses and Technological Evolution of Ophthalmology.

Medical imaging is the mainstay of clinical diagnosis and management. Optical coherence tomography (OCT) is a non-invasive imaging technology that has revolutionized the field of ophthalmology. Since its introduction, OCT has undergone significant improvements in image quality, speed, and resolution, making it an essential diagnostic tool for various ocular pathologies. OCT has not only improved the diagnosis and management of ocular diseases but has also found applications in other fields of medicine. In this manuscript, we provide a brief overview of the history of OCT, its current uses and diagnostic capabilities to assess the posterior segment of the eye, and the evolution of this technology from time-domain (TD) to spectral-domain (SD) and swept-source (SS). This brief review will also discuss the limitations, advantages, disadvantages, and future perspectives of this technology in the field of ophthalmology.

Uncovering the Genetics and Physiology behind Optic Neuritis.

Optic neuritis (ON) is an inflammatory condition affecting the optic nerve, leading to vision impairment and potential vision loss. This manuscript aims to provide a comprehensive review of the current understanding of ON, including its definition, epidemiology, physiology, genetics, molecular pathways, therapy, ongoing clinical studies, and future perspectives. ON is characterized by inflammation of the optic nerve, often resulting from an autoimmune response. Epidemiological studies have shown a higher incidence in females and an association with certain genetic factors. The physiology of ON involves an immune-mediated attack on the myelin sheath surrounding the optic nerve, leading to demyelination and subsequent impairment of nerve signal transmission. This inflammatory process involves various molecular pathways, including the activation of immune cells and the release of pro-inflammatory cytokines. Genetic factors play a significant role in the susceptibility to ON. Several genes involved in immune regulation and myelin maintenance have been implicated in the disease pathogenesis. Understanding the genetic basis can provide insights into disease mechanisms and potential therapeutic targets. Therapy for ON focuses on reducing inflammation and promoting nerve regeneration. Future perspectives involve personalized medicine approaches based on genetic profiling, regenerative therapies to repair damaged myelin, and the development of neuroprotective strategies. Advancements in understanding molecular pathways, genetics, and diagnostic tools offer new opportunities for targeted therapies and improved patient outcomes in the future.

Recent Advances of Adipose-Tissue-Derived Mesenchymal Stem Cell-Based Therapy for Retinal Diseases.

With the rapid development of stem cell research in modern times, stem cell-based therapy has opened a new era of tissue regeneration, becoming one of the most promising strategies for currently untreatable retinal diseases. Among the various sources of stem cells, adipose tissue-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic modality due to their characteristics and multiple functions, which include immunoregulation, anti-apoptosis of neurons, cytokine and growth factor secretion, and antioxidative activities. Studies have shown that ADSCs can facilitate the replacement of dying cells, promote tissue remodeling and regeneration, and support the survival and growth of retinal cells. Recent studies in this field have provided numerous experiments using different preclinical models. The aim of our review is to provide an overview of the therapeutic strategies, modern-day clinical trials, experimental models, and potential clinical use of this fascinating class of cells in addressing retinal disorders and diseases.

Non-Arteritic Anterior Ischemic Optic Neuropathy (NA-AION): A Comprehensive Overview.

Non-arteritic anterior ischemic optic neuropathy (NA-AION) represents one of the most important causes of blindness or severely impaired vision in middle-aged and elderly people. Unilateral optic disc edema and abrupt, painless vision loss are its defining features. It is commonly assumed that NA-AION is caused by an ischemic infarction of the optic nerve head, and, although the exact pathogenesis is still unknown, several risk factors and comorbidities associated with its development have been found. NA-AION occurs generally in patients older than 50 years who have small optic discs and vasculopathy risk factors. Even though numerous treatment options have been proposed, no available effective medical or surgical therapy or prophylactic measure for NA-AION currently exists. The purpose of present-day therapeutic strategies is therefore to identify and possibly control any underlying modifiable risk factors, aiming to prevent the development of new NA-AION episodes in the affected and fellow eye. A thorough assessment of NAION, including its history, epidemiology, etiology, pathophysiology, risk factors, associated comorbidities, clinical findings, diagnostic tests, treatment choices, prognosis, and future research, is the goal of this work.

Exploring Deep Cervical Compartments in Head and Neck Surgical Oncology through Augmented Reality Vision: A Proof of Concept.

BACKGROUND: Virtual surgical planning allows surgeons to meticulously define surgical procedures by creating a digital replica of patients' anatomy. This enables precise preoperative assessment, facilitating the selection of optimal surgical approaches and the customization of treatment plans. In neck surgery, virtual planning has been significantly underreported compared to craniofacial surgery, due to a multitude of factors, including the predominance of soft tissues, the unavailability of intraoperative navigation and the complexity of segmenting such areas. Augmented reality represents the most innovative approach to translate virtual planning for real patients, as it merges the digital world with the surgical field in real time. Surgeons can access patient-specific data directly within their field of view, through dedicated visors. In head and neck surgical oncology, augmented reality systems overlay critical anatomical information onto the surgeon's visual field. This aids in locating and preserving vital structures, such as nerves and blood vessels, during complex procedures. In this paper, the authors examine a series of patients undergoing complex neck surgical oncology procedures with prior virtual surgical planning analysis. For each patient, the surgical plan was imported in Hololens headset to allow for intraoperative augmented reality visualization. The authors discuss the results of this preliminary investigation, tracing the conceptual framework for an increasing AR implementation in complex head and neck surgical oncology procedures.

Surgical Treatment of Spheno-Orbital Meningiomas: A Systematic Review and Meta-Analysis of Surgical Techniques and Outcomes.

BACKGROUND: Spheno-orbital meningiomas (SOMs) are rare tumors arising from the meninges surrounding the sphenoid bone and orbital structures. Surgical resection is the primary treatment approach for SOMs. Several surgical approaches have been described during the decades, including microsurgical transcranial (MTAs), endoscopic endonasal (EEAs), endoscopic transorbital (ETOAs), and combined approaches, and the choice of surgical approach remains a topic of debate. PURPOSE: This systematic review and meta-analysis aim to compare the clinical and surgical outcomes of different surgical approaches used for the treatment of SOMs, discussing surgical techniques, outcomes, and factors influencing surgical decision making. METHODS: A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on the role of surgery for the treatment of SOMs until 2023. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications. RESULTS: A total of 59 studies comprising 1903 patients were included in the systematic review and meta-analysis. Gross total resection (GTR) rates ranged from 23.5% for ETOAs to 59.8% for MTAs. Overall recurrence rate after surgery was 20.7%. Progression-free survival (PFS) rates at 5 and 10 years were 75.5% and 49.1%, respectively. Visual acuity and proptosis improvement rates were 57.5% and 79.3%, respectively. Postoperative cranial nerve (CN) focal deficits were observed in 20.6% of cases. The overall cerebro-spinal fluid (CSF) leak rate was 3.9%, and other complications occurred in 13.9% of cases. MTAs showed the highest GTR rates (59.8%, 95%CI = 49.5-70.2%; p = 0.001) but were associated with increased CN deficits (21.0%, 95%CI = 14.5-27.6%). ETOAs had the lowest GTR rates (23.5%, 95%CI = 0.0-52.5%; p = 0.001), while combined ETOA and EEA had the highest CSF leak rates (20.3%, 95%CI = 0.0-46.7%; p = 0.551). ETOAs were associated with better proptosis improvement (79.4%, 95%CI = 57.3-100%; p = 0.002), while anatomical class I lesions were associated with better visual acuity (71.5%, 95%CI = 63.7-79.4; p = 0.003) and proptosis (60.1%, 95%CI = 38.0-82.2; p = 0.001) recovery. No significant differences were found in PFS rates between surgical approaches. CONCLUSION: Surgical treatment of SOMs aims to preserve visual function and improve proptosis. Different surgical approaches offer varying rates of GTR, complications, and functional outcomes. A multidisciplinary approach involving a skull base team is crucial for optimizing patient outcomes.

Considerations of COVID-19 in Ophthalmology.

Since its emergence in early 2020, the SARS-CoV-2 infection has had a significant impact on the entire eye care system. Ophthalmologists have been categorized as a high-risk group for contracting the virus due to the belief that the eye may be a site of inoculation and transmission of the SARS-CoV-2 infection. As a result, clinical ophthalmologists, optometrists, and eyecare professionals have had to familiarize themselves with the ocular manifestations of COVID-19, as well as its treatments and vaccines. The implementation of measures to prevent the transmission of the virus, such as restrictions, lockdowns, telemedicine, and artificial intelligence (AI), have led to substantial and potentially irreversible changes in routine clinical practice, education, and research. This has resulted in the emergence of a new mode of managing patients in a routine clinical setting. This brief review aims to provide an overview of various aspects of COVID-19 in ophthalmology, including the ocular manifestations related to the disease, the modes of transmission of SARS-CoV-2 infection, precautions taken in ophthalmic practice to prevent the spread of the virus, drugs, and vaccines used in the treatment of COVID-19, the impact of the pandemic on patients, clinicians, and the eye care system as a whole, and the future of ophthalmology conditioned by this global pandemic experience.

Pharmaceutical Approaches to Normal Tension Glaucoma.

Normal tension glaucoma (NTG) is defined as a subtype of primary open-angle glaucoma (POAG) in which the intraocular pressure (IOP) values are constantly within the statistically normal range without treatment and represents approximately the 30-40% of all glaucomatous cases. The pathophysiology of this condition is multifactorial and is still not completely well known. Several theories have been proposed to explain the onset and progression of this disease, which can be divided into IOP-dependent and IOP-independent factors, suggesting different therapeutic strategies. The current literature strongly supports the fundamental role of IOP in NTG. The gold standard treatment for NTG tends to be based on the lowering IOP even if "statistically normal". Numerous studies have shown, however, that the IOP reduction alone is not enough to slow down or stop the disease progression in all cases, suggesting that other IOP-independent risk factors may contribute to the NTG pathogenesis. In addition to IOP-lowering strategies, several different therapeutic approaches for NTG have been proposed, based on vaso-active, antioxidant, anti-inflammatory and/or neuroprotective substances. To date, unfortunately, there are no standardized or proven treatment alternatives for NTG when compared to traditional IOP reduction treatment regimes. The efficacy of the IOP-independent strategies in decreasing the risk or treating NTG still remains inconclusive. The aim of this review is to highlight strategies reported in the current literature to treat NTG. The paper also describes the challenges in finding appropriate and pertinent treatments for this potentially vision-threatening disease. Further comprehension of NTG pathophysiology can help clinicians determine when to use IOP-lowering treatments alone and when to consider additional or alternatively individualized therapies focused on particular risk factors, on a case-by-case basis.

Topography-Guided Transepithelial Photorefractive Keratectomy for the Treatment of Persistent and Visually-Significant Adenoviral Corneal Infiltrates.

Purpose: To evaluate visual and refractive outcomes of customized photorefractive keratectomy (PRK) in subjects with persistent subepithelial corneal opacities secondary to adenoviral epidemic keratoconjunctivitis (EKC). Patients and Methods: Prospective study, which recruited patients with persistent and visually-significant post-EKC corneal opacities unresponsive to prolonged topical therapy (6 months or more). Outcome measures: uncorrected and best-corrected distance visual acuity, subjective refractive astigmatism, keratometric astigmatism, spherical equivalent, minimum corneal thickness, and corneal morphological irregularity index. Subjects were followed for 12 months post-treatment. Results: Eighteen eyes of 18 patients aged between 32 and 75 years treated with topography-guided transepithelial PRK with iRes excimer laser (iVIS Technologies, Taranto, Italy) from June 2020 to July 2021. After 12 months, the mean UDVA improved from 1.0±0.00LogMAR pre-op to 0.15±0.154LogMAR, and the mean CDVA improved from 0.4±0.41LogMAR pre-op to 0.0±0.00LogMAR. With respect to UDVA, all treated eyes (100%) showed an improvement of 6 ETDRS lines or more and with respect to CDVA, 9 out of 18 eyes (50%) showed an improvement of 6 ETDRS lines or more. The mean ablation depth was 54.7±5.9µm. A statistically significant improvement was observed in all topographic indices. No infiltrate recurrence, post-treatment corneal haze, ocular hypertension or other side effects were observed throughout the follow-up period. Conclusion: Topography-guided PRK could be considered an effective and safe treatment option to improve visual acuity in patients affected by persistent and visually-significant subepithelial corneal infiltrates caused by EKC.