Ocular Chronic Graft Versus-Host Disease after Hematopoietic Stem Cell Transplantation

Graft-versus-host disease (GVHD) is a potentially severe complication that may develop in different tissues including the eye after allogenic hematopoietic stem cell transplantation (HSCT). The purpose of this research project was to evaluate ocular surface parameters of patients undergoing HSCT before and after transplantation, and to correlate them with clinical and HSCT features. Data from the charts of ninety-three patients affected by hematological malignancies undergoing HSCT were collected. Values of Ocular Surface Disease Index, Schirmer Test type I, Tear Film Break-up Time, ocular surface staining and Meibomian Gland Dysfunction score obtained before HSCT and 3-6 months after were retrieved from charts. Diagnosis and staging of Dry Eye disease (DED) was performed according to Dry Eye WorkShop criteria. GVHD was classified according to the National Institutes of Health (NIH) 2015 Criteria. Odds ratios for DED onset after HSCT were estimated for demographic, ocular, hematological and HSCT features. Dry eye disease was diagnosed before HSCT in 50 (53%) of the patients, mostly of hyper-evaporative profile. After HSCT all ocular parameters significantly worsened with no change in DE profile. A 51% of incident cases (22 on the 43 non-DE subjects) were reported. Increasing recipient age and female sex, higher CD34+ cells infused, donor-recipient sex mismatch (males receiving from females), related donors, and peripheral blood cells as stem cell source were associated with a significant higher incidence of DED after HSCT. Systemic chronic GVHD was diagnosed in 42% while ocular GVHD in 35.5% of the patients, which decreased to 12% when taking into account only incident cases. In conclusion, a high DE prevalence was shown already before HSCT. Therefore, an ocular surface assessment should be recommended already before HSCT for early DED diagnosis and treatment. This new protocol also could influence the real prevalence of ocular GVHD after HSCT and its severity

Dealing with the Persistent Pathogenic Issues of Dry Eye Disease: The Importance of External and Internal Stimuli and Tissue Responses

The immune system plays a central role in protecting the ocular surface from exogenous and endogenous insults, maintaining tissue homeostasis thanks to the mechanism of para-inflammation. This physiological adaptive response may induce resident macrophages/monocytes to produce cytokines and growth factors in order to promote epithelial cell recovery. In case of well-controlled para-inflammation, caused by a low amount of stress, cell viability and function are maintained. When stress becomes too intense, there is a response characterized by the activation of autophagic pathways and consequent cell death. Dysregulated homeostasis and chronic sub-clinical inflammation are the starting points for the development of a stable, chronic inflammatory disease, which leads to ocular surface damage, and, in turn, to the onset or progression of chronic dry eye disease (DED). The long-term management of DED should consider all of the pathogenic issues involved in the disease, including the control of persistent external or internal stresses that are capable of activating and maintaining the para-inflammatory adaptive mechanisms, potentially leading to full-blown inflammation. Dysregulated para-inflammation can be corrected by means of the prolonged use of tear substitutes containing minimal doses of safe corticosteroids or other anti-inflammatory molecules (e.g., corticosteroid, cyclosporine) in order to re-equilibrate ocular surface homeostasis

Outcomes of serial sessions of Activa mask combined with intense pulsed light therapy in patients with Meibomian gland dysfunction

Background: To evaluate the effects on ocular surface signs and symptoms of serial sessions of heating and vibrating eye mask followed by intense pulsed light (IPL) therapy for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD). Methods: Consecutive patients with MGD whose signs and symptoms were not satisfactorily controlled with conventional therapy were included. Patients received 3 treatments performed at day 1, 15, and 45 incorporating a session with a newly-developed eye mask (Activa, SBS Sistemi, Turin, Italy) immediately followed by IPL therapy (E > Eye device, E-Swin, Paris, France). Patients were examined before the first session (T0) and 30 days after the last session (T1) for the measurement of: noninvasive break-up time (NIBUT); lipid layer thickness (LLT); tear meniscus height (TMH); meibomian gland loss (MGL); tear osmolarity. Ocular discomfort symptoms were ascertained by ocular surface disease index (OSDI) questionnaire. Results: Thirty patients were ultimately included in the study. At T1, all objective ocular surface parameters improved significantly, except for TMH: NIBUT and LLT increased from 6.4 ± 1.7 to 8.6 ± 1.7 s and from 57.7 ± 15.5 to 81.3 ± 12.0 μm (all P < 0.001), while MGL and tear osmolarity decreased from 21.1 ± 17.3 to 17.0 ± 14.1% and from 302.0 ± 8.5 to 295.7 ± 6.9 mOsm/L (respectively, P = 0.004 and P < 0.001). In parallel, OSDI score decreased significantly from 49.8 ± 13.5 to 29.8 ± 10.6 (P < 0.001). In the historical control group of patients who underwent only IPL, NIBUT, LLT, tear osmolarity and OSDI improved significantly but not MGL and TMH. Conclusions: Serial sessions incorporating the application of an eye mask producing heating and vibration immediately followed by IPL therapy are able to improve all ocular surface parameters as well as ocular discomfort symptoms in MGD patients

Ocular Manifestations and Complications of Patent Foramen Ovale: A Narrative Review

Patent foramen ovale (PFO) is a prevalent congenital cardiac anomaly associated with a persistent opening between the atrial septum, allowing communication between the left and right atria. Despite often being asymptomatic, PFO can lead to various clinical presentations, including cryptogenic stroke and other embolic events. Transient visual disturbances, alterations in the visual field, migraine with aura, impaired eye movement and endogenous eye infections may prompt patients to seek ophthalmological consultation. Understanding these diverse clinical scenarios is crucial for early detection, appropriate management and mitigating the morbidity burden associated with PFO. This narrative review aims at examining the spectrum of clinical presentations of ocular pictures associated with PFO. The pathophysiology, diagnosis and treatment methods for PFO will be described, emphasizing the importance of a multidisciplinary approach involving ophthalmologists, cardiologists, neurologists and imaging specialists. In the future, prospective studies and clinical trials are warranted to provide further insights into the preventive role and optimal therapeutic strategies for managing PFO-related ocular complications, ultimately guiding clinical decision making and optimizing patient care

Short-Term Effects of a Novel Eye Mask Producing Heat and Vibration for the Treatment of Meibomian Gland Dysfunction: A Pilot Study

Purpose. To investigate the short-term effects on tear film parameters and ocular symptoms of a novel eye mask producing heat and vibration developed for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD). Methods. This is a pilot study including the first 20 consecutive patients (6 males, 14 females; mean age 52.4 +/- 16.8 years) who were treated with a novel eye mask producing heat (42 degrees) and vibration (up to 20 Hz) (Activa, SBS Sistemi, Turin, Italy) for 15 minutes. The treatment incorporates 2 phases in the following chronological order: 5 minutes of heating (phase I); 10 minutes of combination of heating and vibration (phase II). Noninvasive ocular surface examination was carried out before (T0) and 30 minutes after the mask session (T1) by means of Idra (SBS Sistemi, Turin, Italy) for the measurement of noninvasive break-up time (NIBUT) and lipid layer thickness (LLT). Patients' satisfaction after treatment was ascertained by asking the patients whether they perceived improvement from their baseline symptoms according to a 5-grade scale: none = 0; trace = 1; mild = 2; moderate = 3; high = 4. Results. All patients completed regularly the mask session and no device-related adverse events were noted. NIBUT improved significantly from T0 to T1 (from 7.2 +/- 1.8 s to 8.1 +/- 2.1; P = 0.014). In parallel, also LLT improved from from T0 to T1 (72.5 +/- 13.9 nm to 83.1 +/- 16.1; P = 0.016). Seven patients (35% of the total) had a moderate satisfaction (grade 3) while 13 patients (65%) had a high satisfaction (grade 4) with treatment. Conclusions. This eye mask represents a novel well tolerated tool in the armamentarium of MGD treatments. Thirty minutes after the session, NIBUT and LLT increased significantly; furthermore, all patients reported an improvement of discomfort symptoms with a moderate to high satisfaction with treatment

Umbilical Cord Blood and Serum for the Treatment of Ocular Diseases: A Comprehensive Review

Several blood derivatives have been proposed for the treatment of various ocular diseases that affect either the anterior or the posterior segment of the eye. Blood sources may range from the patient's own peripheral blood (autologous) to donor tissues, mainly allogeneic peripheral blood and umbilical cord blood (UCB). The utilization of the latter permits the collection of a large amount of serum all at once, and is characterized by therapeutic feasibility in patients with a poor general condition or anemia and blood dyscrasia. Products derived from UCB have two potential uses. First, serum in the form of eye drops can be applied topically onto the ocular surface to efficiently treat anterior segment disorders such as dry eye syndrome or corneal epithelial defects with different etiologies. The rationale for and efficacy of this application derive from the high concentrations of biologically active components and growth factors in UCB, which can nourish the ocular surface. Second, UCB is a source of stem cells, which are used in the field of regenerative medicine because they differentiate into various mature cells, including corneal and retinal cells. Therefore, UCB-derived stem cells have been proposed as a replacement therapy for the treatment of retinal and optic nerve diseases, given that current standard treatments often fail. The present review explores the clinical results that have been obtained using UCB-derived products in the field of ophthalmology, as well as the current limitations of those products in this field. Furthermore, given the promising development of UCB-based therapies, possible future directions in this area are discussed

Effects of Serial Sessions of Activa Mask for the Treatment of Meibomian Gland Dysfunction

Introduction: To analyze outcomes on objective ocular surface parameters and subjective symptoms of serial weekly sessions using the Activa mask in patients with meibomian gland dysfunction (MGD). Methods: This is a prospective study including patients with symptomatic MGD who were treated with four weekly sessions using the Activa mask (SBM Sistemi, Turin, Italy). Noninvasive ocular surface examination was carried out before (T0) and 2 weeks after the last mask session (T1) using Idra (SBM Sistemi, Turin, Italy) for the measurement of: (1) noninvasive break-up time (NIBUT); (2) lipid layer thickness (LLT); (3) tear meniscus height (TMH); (4) meibomian gland loss (MGL) of upper and lower eyelids. The I-Pen tear osmolarity system (I-Med Pharma Inc, Dollard-des Ormeaux, Quebec, Canada) was used to measure tear osmolarity values. Ocular discomfort symptoms were ascertained by means of the ocular surface disease index (OSDI) questionnaire. Results: All 25 patients (11 males, 14 females; mean age 57.1 ± 11.9 years) regularly completed the cycle of four mask sessions. No patients used prohibited medications, and no device-related adverse events were noted. At T1, mean values of NIBUT and LLT increased significantly compared to T0 (respectively from 6.0 ± 1.4 to 6.6 ± 1.2 s, P = 0.043, and from 53.2 ± 17.4 to 65.3 ± 16.3 nm, P < 0.001), while mean values of MGL and tear osmolarity decreased significantly (respectively from 17.1 ± 9.3 to 15.1 ± 8.0%, P = 0.014, and from 307.3 ± 12.2 to 301.5 ± 6.8 mOsm/l, P = 0.005). In parallel, OSDI score reduced significantly from 62.4 ± 11.7 at T0 to 34.5 ± 11.2 at T1 (P < 0.001). Conclusion: Weekly serial sessions using the Activa mask significantly improved objective parameters of the ocular surface as well as subjective ocular discomfort symptoms in patients with recalcitrant MGD. As a further benefit from the treatment, patients were able to avoid the use of concomitant medications, apart from tear substitutes, throughout the study

Diagnostic Performance of a Novel Noninvasive Workup in the Setting of Dry Eye Disease

Purpose. To evaluate the diagnostic performance of a novel noninvasive automated workup employed for the diagnosis of dry eye disease (DED). Methods. One hundred patients with mild to moderate DED and 100 matched control subjects were enrolled in this cross-sectional study. Ocular surface examinations were carried out by means of IDRA Plus (SBM Sistemi, Turin, Italy), which allows the automated evaluation of noninvasive breakup time (NIBUT), lipid layer thickness (LLT), tear meniscus height (TMH), infrared meibography for the measurement of meibomian gland loss (MGL), and blinking analysis. Continuous variables were compared between patients with DED and controls by using the Mann-Whitney U test. The area under the curve (AUC) of receiver operating characteristic curves was calculated. The correlations between ocular surface parameters were evaluated with Pearson correlation analysis. Results. Patients with DED showed significantly lower values of NIBUT, LLT, and TMH compared to controls (6.9 +/- 2.5 vs 10.4 +/- 2.4 s, P < 0.001; 64.6 +/- 20.3 vs 73.4 +/- 21.9 nm, P = 0.003; 0.231 +/- 0.115 vs 0.289 +/- 0.164, P = 0.012, respectively). Conversely, no significant differences were observed for MGL and blinking analysis (both P > 0.05). NIBUT had the highest diagnostic power (AUC = 0.841, sensitivity = 0.89, and specificity = 0.69), followed by LLT (AUC = 0.621, sensitivity = 0.89, and specificity = 0.55), TMH (AUC = 0.606, sensitivity = 0.57, and specificity = 0.63), blink analysis (AUC = 0.533, sensitivity = 0.48, and specificity = 0.59), and MGL (AUC = 0.531, sensitivity = 0.54, and specificity = 0.48). In patients with DED, NIBUT showed a significant correlation with TMH (R = 0.347, P = 0.002) and blinking analysis (R = 0.356, P < 0.001), while blinking analysis was negatively correlated with MGL (R = -0.315, P = 0.008). Conclusions. The automated noninvasive workup validated in this study may be a useful tool for reaching a noninvasive diagnosis of DED with a good performance, especially for NIBUT

A randomized clinical trial assessing theranostic-guided corneal cross-linking for treating keratoconus: the ARGO protocol

The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination