Curcumin in Retinal Diseases: A Comprehensive Review from Bench to Bedside.

Recent evidence in basic science is leading to a growing interest in the possible role of curcumin in treating retinal diseases. Curcumin has been demonstrated to be able to modulate gene transcription and reduce ganglion cell apoptosis, downgrade VEGF, modulate glucose levels and decrease vascular dysfunction. So far, the use of curcumin has been limited by poor bioavailability; to overcome this issue, different types of carriers have been used. Multiple recent studies disclosed the efficacy of using curcumin in treating different retinal conditions. The aim of this review is to comprehensively review and discuss the role of curcumin in retinal diseases from bench to bedside.

Excimer laser tissue interactions in the cornea.

Excimer lasers induces significant changes to corneal structure and corneal biomechanics. The aim of this paper is to describe all laser-tissue interactions which are relevant for clinical practice, particularly, we will focus on laser ablations profiles, causes of regression and haze and prevention of those. At last the manuscript will describe the impact on corneal biomechanics of different Laser Vision Corrections techniques.

Safety of silicone oils as intraocular medical device: An in vitro cytotoxicity study.

This study aimed to assess the cytotoxic effect of low molecular weight components (LMWC) and conventional silicone oils (SOs) 1000 cSt with different degree of purification (raw, intermediate, and purified) using in vitro cytotoxicity tests. Direct contact cytotoxicity tests were performed in BALB 3T3 and human retinal pigment epithelial cells (ARPE-19) using quantitative and qualitative evaluation according to the ISO 10993-5 (2009) standards. Conventional SOs 1000 cSt in form of raw, intermediate (intermediate product obtained during distillation process), and purified SO (final product after distillation) and a concentrate of LMWC (including siloxane chains with molecular weight up to 1557 g/mol) were directly applied to 100% of cell layer area for 24 h. Cell viability was quantified using 3-(4,5-dimethylthiazole-2-yl)-2,5-28 diphenyltetrazolium bromide (MTT) and neutral red uptake assays in ARPE-19 and BALB3T3, respectively. All tested samples, including the concentrate of LMWC, resulted to be not cytotoxic according to ISO 10993-5 in both qualitative and quantitative evaluations. However, the cellular viability was significantly higher in the intermediate and purified SO compared with the raw SO in ARPE-19 cells. No reduction in cell viability was detected by LMWC. The absence of cytotoxicity was observed for all tested samples in both BALB3T3 and ARPE-19 after 24 h of application. A direct cytotoxic effect is not likely to be involved in the potential complications related to SO and LMWC. Long-term potential adverse effects of SO could be related to the raw material and to different concentrations of LMWC.

Optic disc drusen: a systematic review : Up-to-date and future perspective.

BACKGROUND: Optic disc drusen (ODD) are acellular deposits in the prelaminar optic nerve head. The most accredited theory is that they are secondary to abnormalities in axonal metabolism and degeneration, but the pathogenesis is not clear to date. CLINICAL MANIFESTATION: Although ODD are often considered a benign condition, the great majority of patients with ODD show visual field defects and are at higher risk for developing anterior ischemic optic neuropathy. ODD are classified as superficial or buried, with the latter being often misdiagnosed as papilledema with optic nerve head swelling, leading to an unnecessary investigation for causes of increased intracranial pressure. AIM: The recent technological improvements in OCT imaging which allowed an earlier and more certain diagnosis even of the smallest ODD, renovated the interest around this pathology. However, an updated systematic review is still missing. Therefore, the aim of this work is to provide a concise yet comprehensive overview of the current state of art, focusing on pathophysiology, clinical presentation, diagnostic methods, treatment modalities and potential future perspectives of this condition.

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.

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.

Ocular-Surface Regeneration Therapies for Eye Disorders: The State of the Art.

The ocular surface is a complex structure that includes cornea, conjunctiva, limbus, and tear film, and is critical for maintaining visual function. When the ocular-surface integrity is altered by a disease, conventional therapies usually rely on topical drops or tissue replacement with more invasive procedures, such as corneal transplants. However, in the last years, regeneration therapies have emerged as a promising approach to repair the damaged ocular surface by stimulating cell proliferation and restoring the eye homeostasis and function. This article reviews the different strategies employed in ocular-surface regeneration, including cell-based therapies, growth-factor-based therapies, and tissue-engineering approaches. Dry eye and neurotrophic keratopathy diseases can be treated with nerve-growth factors to stimulate the limbal stem-cell proliferation and the corneal nerve regeneration, whereas conjunctival autograft or amniotic membrane are used in subjects with corneal limbus dysfunction, such as limbal stem-cell deficiency or pterygium. Further, new therapies are available for patients with corneal endothelium diseases to promote the expansion and migration of cells without the need of corneal keratoplasty. Finally, gene therapy is a promising new frontier of regeneration medicine that can modify the gene expression and, potentially, restore the corneal transparency by reducing fibrosis and neovascularization, as well as by stimulating stem-cell proliferation and tissue regeneration.

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.

ROCK Inhibitors in Corneal Diseases and Glaucoma-A Comprehensive Review of These Emerging Drugs.

Rho kinase (ROCK) inhibitors have gained significant attention as emerging novel treatment options in the field of ophthalmology in recent years. The evidence supporting their efficacy in glaucoma and corneal pathology includes both in vitro and clinical studies. Among the available options, ripasudil and netarsudil have emerged as the leading ROCK inhibitors, and some countries have approved these therapeutic options as treatments for glaucoma. Various dosing regimens have been studied, including monotherapy and combination therapy, especially for patients with secondary glaucoma who are already on multiple medications. Another rising application of ROCK inhibitors includes their use as an adjunct in surgical procedures such as Descemetorhexis Without Endothelial Keratoplasty (DWEK), Descemet Stripping Only (DSO) to accelerate visual recovery, glaucoma surgeries to reduce scarring process and allow better intraocular pressure (IOP) control, or after complicated anterior segment surgery to treat corneal oedema. This article provides a comprehensive overview of the existing literature in the field, offering recommendations for prescribing ROCK inhibitors and also discussing patient selection, drug efficacy, and possible adverse effects.

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.

Posterior stromal ripples increase risk of Descemet's membrane endothelial keratoplasty graft detachment worsening over time.

PURPOSE: To evaluate anterior segment optical coherence tomography (AS-OCT) features of Descemet's membrane endothelial keratoplasty (DMEK) grafts associated with graft attachment worsening over time. METHODS: Retrospective case series on patients who received uncomplicated DMEK surgery and for whom subsequent AS-OCT data were available for analysis. Patients' demographics and surgical details were collected. AS-OCT was analysed for graft detachment axial extension, presence of posterior stromal ripples, quadrant involvement (location and number), degree of detachment extension, peripheral roll, presence and amount of air in the anterior chamber (AC). Features associated with re-bubbling and graft detachment worsening over time were identified. RESULTS: A total of 147 patients with a mean age of 70.8 ± 9.8 years (63% females) were included. AS-OCT was performed at 2.9 ± 2.4 days after surgery. AS-OCT factors associated with re-bubbling were posterior stromal ripples (p = 0.004) and detachment axial extension (p < 0.001). At first follow-up, of the 147 DMEK, 67 showed complete attachment and 80 partial detachment. In those cases of initially completely attached grafts, posterior stromal ripples were associated with the risk of subsequent graft detachment (p = 0.014) together with recipient age (p = 0.043), phaco-combined surgery (p = 0.018) and AS-OCT timing (p = 0.033); while, in the initially partially detached grafts, detachment worsening was associated with posterior stromal ripples (p = 0.025), detachment axial extension (p = 0.003), degrees of detachment involvement (p = 0.029), peripheral roll-in shape (p = 0.033) and presence of air in the AC (p = 0.032). Relative risk (RR) of graft detachment worsening in patients with moderate/severe posterior stromal ripples was 1.75 (95% CI = 1.09-2.81). CONCLUSION: Posterior stromal ripples and detachment axial extension >1/3 of graft surface area were the main risk factors for detachment worsening over time, and patients showing these features should be monitored closely to identify the need for re-bubbling at an early stage, thus improving surgical outcomes.

Managing Post-Keratoplasty Astigmatism: High-Tech vs. Low-Tech Imaging Techniques for Guiding Suture Manipulation.

Astigmatism is a visually significant condition that can develop after keratoplasty. The management of post-keratoplasty astigmatism can be performed both when transplant sutures are in place and when they have been removed. Fundamental for astigmatism management is its identification and characterization in terms of type, amount, and direction. Commonly, post-keratoplasty astigmatism is evaluated through corneal tomography or topo-aberrometry; however, many other techniques can be used in case these instruments are not readily available. Here, we describe several low-tech and high-tech techniques used for post-keratoplasty astigmatism detection in order to quickly understand if it contributes to low vision quality and to determine its characteristics. The management of post-keratoplasty astigmatism through suture manipulation is also described.

Importance of Corneal Angiography in Subclinical Limbitis in a Case of Atopic Keratoconjunctivitis.

PURPOSE: The aim of this study was to report corneal angiography features in subclinical limbitis in a patient with atopic keratoconjunctivitis. METHODS: This is a case report. RESULTS: A 22-year-old woman with a medical history of atopic keratoconjunctivitis was referred for bilateral corneal neovascularization with scarring. On examination, no signs of active disease were noticed at the slit lamp. Ocular surface angiography detected active corneal limbitis, showing as limbal leakage at fluorescein angiography in the early phase and leakage after indocyanine green angiography in the late phase. The patient was treated with topical corticosteroid. At follow-up, the fluorescein angiography and indocyanine green angiography no longer showed limbal leakage, whereas the slit lamp examination was unchanged. CONCLUSIONS: Active allergic corneal limbitis may present as subclinical inflammation, with no signs of activity at the slit lamp examination. Therefore, its diagnosis can be challenging without the use of corneal angiography.

Blast Wound Dehiscence During Descemet Membrane Endothelial Keratoplasty Rebubbling in a Previous Penetrating Keratoplasty: A Case Report.

PURPOSE: The purpose of this study was to describe a rare complication of Descemet membrane endothelial keratoplasty (DMEK) rebubbling. METHODS: An 86-year-old woman with bilateral penetrating keratoplasty (PK) performed 20 years previously for Fuchs endothelial dystrophy underwent DMEK surgery for endothelial corneal decompensation in the left eye. Surgery was complicated in the postoperative period by repeated DMEK graft detachments requiring rebubbling. RESULTS: The third rebubbling procedure caused a traumatic PK wound dehiscence at the graft-host junction with full-thickness opening of approximately 180 degrees. PK wound dehiscence was resutured in the theater, DMEK lenticule was removed from the eye, and the full-thickness graft was repeated. CONCLUSIONS: DMEK graft rebubbling in patients with previous PK may lead to traumatic wound dehiscence. Avoidance of excessive increases in intraocular pressure during the rebubbling procedure should be encouraged to decrease the risk of this rare complication.

Management of refractory and recurrent macular holes: A comprehensive review.

The primary repair of full-thickness macular holes (FTMHs) through pars plana vitrectomy with internal limiting membrane peeling and gas tamponade is the current standard of practice and offers a high closure rate of approximately 90%. On the contrary, the surgical management of refractory (or persistent) and recurrent FTMHs is still a challenging and controversial topic in vitreoretinal surgery as multiple options have been suggested, particularly over the last few years, with no consensus regarding any appropriate selection criteria or the best surgical option. Moreover, the presence of various case series / interventional studies presenting comparable outcomes, as well as the absence of studies with a direct comparison of different surgical techniques, may result in confusion. We provide a structured and comprehensive overview of the different surgical options currently available for the secondary repair of refractory and recurrent FTMHs. In addition to an update on epidemiology, diagnosis and description of the surgical steps, we highlight the evidence available to support each of the described surgical techniques, specifically focusing on the presumed mechanisms of hole closure, advantages, and known prognostic factors.

Association of alkaptonuria and low dose nitisinone therapy with cataract formation in a large cohort of patients.

Homogentisic acid (HGA) lowering, disease modifying off-label nitisinone therapy has been used in the United Kingdom National Alkaptonuria Centre (NAC) since 2012. This study evaluated the serendipitous observation of cataract in a large cohort of patients with the very rare disease alkaptonuria (AKU), over a 5-year period. Patients with AKU who attended the NAC since 2012. Standard physical examination and ocular assessment, including photographs of the crystalline lens were taken before commencement of nitisinone 2 mg daily and annually over 5 years. Photographs were randomised and graded by two independent observers using the WHO cataract classification. AKU patients who did not receive nitisinone were included as a control group. HGA was measured on acidified 24 h urine (u-HGA24) and HGA and tyrosine in fasting acidified serum samples (sHGA, sTYR) at each visit. Patients without suitable lens images were excluded. Cataract (mean grade 1) was noted at baseline in 47 out of 62 (76%) with a mean (SD) age of 44 (14) years. In nitisinone-treated patients, there were significant increases in the mean grade of nuclear (0.18, p < 0.01) and cortical (0.38, p < 0.01) lens opacities over the mean duration of 4.93 years of the study. Worsening of the nuclear cataract and cortical lens opacities by at least 1 grade was noted in 14 out of 46 (30%) and 11 out of 46 (24%) patients, respectively. There is an increased prevalence and progression of cataract in AKU and a possible association of nitisinone with cataract progression.

OCT Analysis of Retinal Pigment Epithelium in Myopic Choroidal Neovascularization: Correlation Analysis with Different Treatments.

Objective: The objective of this study was to analyze the status of the retinal pigment epithelium (RPE) by means of the spectral domain optical coherence tomography (SD-OCT) overlying the myopic neovascular lesions in the involutive phase, looking for any correlations between the status of the RPE and the size of the lesions and the type and duration of the treatment. Methods: SD-OCT examinations of 83 consecutive patients with myopic choroidal neovascularization (CNV) were reviewed and divided into two groups: group A, patients with CNV characterized by uniformity of the overlying RPE, and group B, patients with CNV characterized by non-uniformity of the overlying RPE. Results: The median lesion area, major diameter, and minimum diameter were, respectively, 0.42 mm2 (0.30−1.01 mm2), 0.76 mm2 (0.54−1.28 mm2), and 0.47 mm2 (0.63−0.77 mm2) in group A, and 1.60 mm2 (0.72−2.67 mm2), 1.76 mm2 (1.13−2.23 mm2), and 0.98 mm2 (0.65−1.33 mm2) in group B. These values were lower in group A than in group B (p < 0.001). The number of treatments with a period free of disease recurrence for at least 6 months was greater (p < 0.010) in group B (6.54 ± 2.82) than in group A (3.67 ± 2.08), and treatments include intravitreal anti-vascular endothelial growth factor injection, photodynamic therapy, or both. Conclusions: Our results showed that the size of myopic neovascular lesion influences the development of a uniform RPE above the lesion and therefore the disease prognosis. The presence of uniform RPE was found to be extremely important in the follow-up of patients with myopic CNV, as it influences the duration of the disease and the number of treatments required.

Viscoelastic-assisted inverted cover and free ILM flap techniques.

statement: Surgical technique: an innovative way of using cohesive viscoelastic to stabilize the ILM flap during the cover inverted-flap and free-flap procedures.Summary statement: Surgical technique: an innovative way of using cohesive viscoelastic to stabilize the ILM flap during the covering step in the inverted-flap and free-flap procedures.

Novel Technique for Descemetorhexis Under Ophthalmic Viscosurgical Devices and Air.

PURPOSE: The aim of this study was to describe a novel technique for descemetorhexis that combines the advantages of stable anterior chamber (AC) associated with ophthalmic viscosurgical devices and optimal surgical visualization seen with air to overcome the issues of poor Descemet membrane (DM) visibility or AC instability when each is used alone. METHODS: This study is a description of a new surgical approach. RESULTS: We describe a new technique for performing descemetorhexis. The simultaneous presence of cohesive ophthalmic viscosurgical device and air in the AC offers optimal DM visualization and guarantees a stable AC during this surgical step. It does not require an additional incision for an AC maintainer. CONCLUSIONS: The described technique may facilitate the surgical step of descemetorhexis, offering improved AC stability and better visualization of the DM. It may reduce early postoperative graft detachment due to the presence of residues of the recipient's diseased DM.