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

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

Ophthalmic Manifestations in Patients with Blood Malignancies.

Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 and examines the common ocular complications associated with blood cancers. Ocular complications from primary disease include mass effects from ocular adnexal lymphomas and intraocular lymphomas, with B-cell lymphomas accounting for 95% of primary ocular presentations. Secondary disease involvement from systemic hematological malignancies can lead to a wide range of ocular manifestations, such as leukemic retinopathy. Furthermore, toxicity from antineoplastic therapies and ocular graft versus host disease (oGVHD) after hematopoietic stem cell transplantation present additional risks to ocular health. In conclusion, ocular complications in blood cancer patients are an integral part of patient management, requiring regular ophthalmic evaluations and close collaboration between oncologists and ophthalmologists. Advances in therapy and an increased focus on early symptom recognition are essential for preserving vision and enhancing patient quality of life.

Feasibility of Tear Meniscus Height Measurements Obtained with a Smartphone-Attachable Portable Device and Agreement of the Results with Standard Slit Lamp Examination.

PURPOSE: We aimed to evaluate the feasibility of using a novel device, the Smart Eye Camera (SEC), for assessing tear meniscus height (TMH) after fluorescein staining and the agreement of the results with measurements obtained using standard slit lamp examination. METHODS: TMH was assessed using both SEC and conventional slit lamp examination. The images were analyzed using the software ImageJ 1.53t (National Institutes of Health, Bethesda, MD, USA). A common measurement unit scale was established based on a paper strip, which was used as a calibration marker to convert pixels into metric scale. A color threshold was applied using uniform parameters for brightness, saturation, and hue. The images were then binarized to black and white to enhance the representation of the tear menisci. A 2 mm area around the upper and lower meniscus in the central eye lid zone was selected and magnified 3200 times to facilitate manual measurement. The values obtained using SEC were compared with those obtained with a slit lamp. RESULTS: The upper and lower TMH values measured using the SEC were not statistically different from those obtained with a slit lamp (0.209 ± 0.073 mm vs. 0.235 ± 0.085, p = 0.073, and 0.297 ± 0.168 vs. 0.260 ± 0.173, p = 0.275, respectively). The results of Bland-Altman analysis demonstrated strong agreement between the two instruments, with a mean bias of -0.016 mm (agreement limits: -0.117 to 0.145 mm) for upper TMH and 0.031 mm (agreement limits: -0.306 to 0.368 mm) for lower TMH. CONCLUSIONS: The SEC demonstrated sufficient validity and reliability for assessing TMH in healthy eyes in a clinical setting, demonstrating concordance with the conventional slit lamp examination.

Longitudinal Observation of Two Giant Peripheral Atrophic Retinal Holes Left Untreated.

In this report, two rare cases of large atrophic peripheral retinal holes are described. Both patients presented during a routine visit without reporting any ocular symptoms. The holes did not exhibit significant risk factors for progression to rhegmatogenous retinal detachment: No signs of posterior vitreous detachment, vitreoretinal tractions, or retinal degeneration were visible. For such asymptomatic cases, international guidelines recommend a strict follow-up schedule; however, the unusual size of the holes raised significant concerns about the management of these retinal breaks. The advantages and disadvantages of laser photo-coagulation treatment were discussed, ultimately favoring a watch-and-wait strategy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:176-178.].

Effect of intralenticular dexamethasone implant: A case report.

INTRODUCTION: Intravitreal dexamethasone (DEX) implant is indicated for the treatment of macular oedema due to diabetic retinopathy, retinal vein occlusion and uveitis. The most common complications are cataract and elevated intraocular pressure (IOP). Accidental injection of DEX implant into the lens is a rare complication and only few papers presented it. CASE PRESENTATION: A 40-year-old man was treated with DEX implant for diabetic macular oedema in both eyes. At 1 week follow-up visit, slit lamp examination showed the DEX implant was located in the crystalline lens of the right eye (RE) without any sign of inflammation, cataract or elevated IOP, so we decided to plan a normal follow-up schedule. Macular oedema relapsed 5 months after the injection in the left eye (LE), whereas the RE did not show any sing of intraretinal or subretinal fluid. Six months after DEX implantation an uneventful phacoemulsification and intraocular lens placement were performed in the RE because of IOP elevation. CONCLUSIONS: The therapeutic effect of DEX implant can be maintained for a longer period of time than intravitreal implant, determining complete reabsorption of macular oedema. Intralenticular implant can be maintained inside the lens until either IOP increases, cataract progresses, or other complications occur.

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

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

Update on coronavirus disease 2019: Ophthalmic Manifestations and Adverse Reactions to Vaccination.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 was one of the most devastating public health issues in recent decades. The ophthalmology community is as concerned about the COVID-19 pandemic as the global public health community is, as COVID-19 was recognized to affect multiple organs in the human body, including the eyes, early in the course of the outbreak. Ophthalmic manifestations of COVID-19 are highly variable and could range from mild ocular surface abnormalities to potentially sight and life-threatening orbital and neuro-ophthalmic diseases. Furthermore, ophthalmic manifestations may also be the presenting or the only findings in COVID-19 infections. Meanwhile, global vaccination campaigns to attain herd immunity in different populations are the major strategy to mitigate the pandemic. As novel vaccinations against COVID-19 emerged, so were reports on adverse ophthalmic reactions potentially related to such. As the world enters a post-pandemic state where COVID-19 continues to exist and evolve as an endemic globally, the ophthalmology community ought to be aware of and keep abreast of the latest knowledge of ophthalmic associations with COVID-19 and its vaccinations. This review is a summary of the latest literature on the ophthalmic manifestations of COVID-19 and the adverse ophthalmic reactions related to its vaccinations.

Large Language Model Advanced Data Analysis Abuse to Create a Fake Data Set in Medical Research.

This quality improvement study evaluates the ability of GPT-4 Advanced Data Analysis to create a fake data set that can be used for the purpose of scientific research.

Recent advances in drug treatments for dry eye disease.

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

Treatments for Ocular Diseases in Pregnancy and Breastfeeding: A Narrative Review.

Pregnancy is a medical condition in which the physiological changes in the maternal body and the potential impact on the developing fetus require a cautious approach in terms of drug administration. Individual treatment, a thorough assessment of the extent of the disease, and a broad knowledge of the therapeutic options and different routes of administration of ophthalmic drugs are essential to ensure the best possible results while minimizing risks. Although there are currently several routes of administration of drugs for the treatment of eye diseases, even with topical administration, there is a certain amount of systemic absorption that must be taken into account. Despite continuous developments and advances in ophthalmic drugs, no updated data are available on their safety profile in these contexts. The purpose of this review is both to summarize the current information on the safety of ophthalmic treatments during pregnancy and lactation and to provide a practical guide to the ophthalmologist for the treatment of eye diseases while minimizing harm to the developing fetus and addressing maternal health needs.

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

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

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.

Impact of topographic localization of corneal ectasia on the outcomes of deep anterior lamellar keratoplasty employing large (9 mm) versus conventional diameter (8 mm) grafts.

OBJECTIVES: Visual and topographic outcomes of large (9.0 mm) versus conventional (8.0 mm) deep anterior lamellar keratoplasty (DALK) for the treatment of keratoconus (KC) were compared in relation to the different localization of the corneal ectasia (within or beyond the central 8.0 mm). METHODS: This is a retrospective, comparative case series. Preoperatively, the topographic extension of the conus was calculated by measuring the distance from the geometric center of the cornea and the outermost point of the corneal ectasia (ectasia <8.0 mm, group A; ectasia ≥8.0 mm, group B). DALK was performed using both small grafts (8.0 mm, group 1) and large grafts (9.0 mm, group 2). Best-corrected visual acuity and topographic astigmatism were evaluated preoperatively (T0) and postoperatively after complete suture removal (1 year, T1). RESULTS: Data from 224 eyes of 196 patients (mean age 37.6 ± 15.1 years) were evaluated. Topographic astigmatism improved from T0 to T1 (4.94 ± 2.92 diopters (D) [95% CI, 4.56-5.33] vs 4.19 ± 2.45 D [95% CI, 3.87-4.51], p = 0.001). There was no significant difference in postoperative topographic cylinder between group 1 and group 2 when considering eyes with corneal ectasia <8.0 mm (group 1 A, 4.15 ± 2.19 D [95% CI, 3.64-4.66] vs group 2 A, 3.65 ± 2.13 D [95% CI, 2.92-4.38], p = 0.14); conversely, the difference was significant considering eyes with corneal ectasia ≥8.0 mm (group 1B, 4.74 ± 2.90 D [95% CI, 4.09-5.38] vs group 2B, 3.68 ± 1.94 D [95% CI, 3.10-4.26], p = 0.02). CONCLUSIONS: Large 9.0-mm DALK provided better anatomical outcomes compared to conventional 8.0-mm DALK, particularly in eyes with corneal ectasia extending beyond the central 8.0 mm.

Widefield and Ultra-Widefield Retinal Imaging: A Geometrical Analysis.

Diabetic retinopathy (DR) often causes a wide range of lesions in the peripheral retina, which can be undetected when using a traditional fundus camera. Widefield (WF) and Ultra-Widefield (UWF) technologies aim to significantly expand the photographable retinal field. We conducted a geometrical analysis to assess the field of view (FOV) of WF and UWF imaging, comparing it to the angular extension of the retina. For this task, we shot WF images using the Zeiss Clarus 500 fundus camera (Carl Zeiss Meditec, Jena, Germany). Approximating the ocular bulb to an ideal sphere, the angular extension of the theoretically photographable retinal surface was 242 degrees. Performing one shot, centered on the macula, it was possible to photograph a retinal surface of ~570 mm2, with a FOV of 133 degrees. Performing four shots with automatic montage, we obtained a retinal surface area of ~1100 mm2 and an FOV of 200 degrees. Finally, performing six shots with semi-automatic montage, we obtained a retinal surface area of ~1400 mm2 and an FOV of 236.27 degrees, which is close to the entire surface of the retina. WF and UWF imaging allow the detailed visualization of the peripheral retina, with significant impact on the diagnosis and management of DR.

Serial Sessions of a Novel Low-Level Light Therapy Device for Home Treatment of Dry Eye Disease.

INTRODUCTION: This study aimed to evaluate the changes that a recently developed at-home device using low-level light therapy (LLLT) produced in signs and symptoms of patients with dry eye disease (DED) owing to meibomian gland dysfunction (MGD). METHODS: In this prospective study, patients with DED owing to MGD not successfully responding to first-line therapy (tear substitutes and eye lid hygiene) were treated with four serial sessions (every other day) of mask based on LLLT technology and dedicated for home use (my-mask®, Espansione Marketing S.p.A., Bologna, Italy). Non-invasive ocular surface examination was carried out by means of Keratograph 5M (Oculus, Wetzlar, Germany) before and after four mask sessions for the evaluation of (i) tear meniscus height (TMH); (ii) first and average non-invasive Keratograph breakup time (NIKBUT); (iii) meibomian gland loss (MGL). Ocular Surface Disease Index (OSDI) questionnaire was used to assess ocular discomfort symptoms. RESULTS: Overall, 17 patients (3 male, 14 female; mean age 61.47 ± 11.93 years) were enrolled and all of them regularly completed the entire cycle of four sessions without reporting any adverse event. The mean values of NIKBUT first and NIKBUT average increased significantly after treatment (from 5.29 ± 2.60 at T0 to 9.04 ± 3.49 s at T1 [P = 0.001] and from 9.40 ± 3.81 to 11.28 ± 2.81 s [P = 0.017]); in parallel, the mean value of TMH increased significantly from 0.27 ± 0.06 to 0.32 ± 0.09 mm (P = 0.029). Conversely, there were not statistically significant differences for MGL (P = 0.346). In addition, the mean value of OSDI score decreased after treatment (from 32.00 ± 7.96 at T0 to 20.71 ± 8.03 at T1; P < 0.001). CONCLUSIONS: One week of serial sessions of a newly developed LLLT device for home use significantly improved tear film production and stability along with ocular discomfort symptoms in patients with DED owing to MGD. These findings open up a new scenario for patients with MGD who can enjoy the unique benefits of LLLT at home.