A Novel Ophthalmic Solution Containing Glicopro® Complex for the Treatment of Patients with Dry Eye Disease: Results from a Pilot Study.

(1) Background: Dry eye disease (DED) is a multifactorial ocular surface disease characterized by an imbalance in ocular surface homeostasis, and tear substitutes constitute the first line of treatment. The present study aimed to evaluate the changes in the signs and symptoms of patients with DED treated with a novel tear substitute containing the GlicoPro® complex. (2) Methods: Patients with DED not successfully responding to other tear substitutes were enrolled and treated with a novel ophthalmic solution (two drops four times daily). Patients were examined before starting the study treatment (T0) and after 30 (T1) and 60 (T2) days of treatment by means of Keratograph for the evaluation of the following: (i) tear meniscus height (TMH); (ii) noninvasive Keratograph break-up time (NIKBUT); (iii) bulbar redness; and (iv) infrared meibography. The SANDE questionnaire was administered to assess ocular discomfort symptoms. Analysis of the tear content of proenkephalin and Met/Leu-enkephalin was also performed. (3) Results: At T2, a significant improvement in NIKBUT first, average, and class, TMH, and SANDE score was found. The tear content of proenkephalins was significantly higher at T1, whereas processed active Met/Leu-enkephalins increased at both T1 and T2. (4) Conclusions: Our novel tear substitute based on GlicoPro® resulted in a significant improvement in ocular discomfort symptoms, tear volume, and stability in the patients treated. The increase in active peptides processed in tears may represent the pathophysiological substrate underlying this finding.

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.

Noninvasive Ocular Surface Workup in Patients with Meibomian Gland Dysfunction Using Microwave-Heated Eye Bag.

Purpose: To report the outcomes of a novel microwave heating device (Blepha EyeBag®) used serially for the treatment of meibomian gland dysfunction (MGD). Patients and Methods: This prospective single center study was conducted at University Magna Graecia of Catanzaro. Patients were instructed to apply the compress twice daily for 15 days and once per day every two days, as reported in the package insert. Outcome measures were i) ocular surface disease index (OSDI) score, ii) tear meniscus height (TMH), iii) non-invasive keratograph break-up time (NIKBUT) (first and average), iv) meiboscore, v) bulbar redness. Evaluations were performed at baseline (T0) after 15 days (T1) and after 45 days of therapy (T2). Results: Overall, 19 patients with MGD (8 males, 11 females; mean age 64.58 ± 9.72 years) were included. The mean value of OSDI score showed a significant decrease from 28.16 ± 17.46 at T0 to 13.69 ± 7.62 at T2 (p=0.008). The mean value of NIKBUT first significantly increased from 6.67 ± 3.51 seconds (s) at T0 to 10.46 ± 4.64 at T2 (p=0.0121); in parallel, the mean value of NIKBUT average increased significantly from 11.09 ± 4.15 s at T0 to 14.95 ± 4.85 at T2 (p=0.0049). No significant differences were detected at each time point for bulbar redness, meiboscore and TMH. Throughout the entire study, no adverse events were recorded. Conclusion: The microwave-heated eye bag treatment is both safe and effective for treatment of MGD, being able to significantly ameliorate both patient-reported symptoms and tear film stability.

Noninvasive screening of ocular surface disease in otherwise healthy patients scheduled for cataract surgery.

PURPOSE: To evaluate prevalence and characteristics of pathological ocular surface findings in healthy patients undergoing cataract surgery using a noninvasive ocular surface workup and a validated questionnaire. DESIGN: Prospective single-centre study (sub-analysis clinical trial no. NCT05754437). METHODS: Healthy patients undergoing senile cataract surgery were screened preoperatively by Oculus Keratograph (K5 M; Oculus GmbH, Wetzlar, Germany) for the evaluation of tear meniscus height (TMH), non-invasive keratograph break-up time (NIKBUT), and meibomian gland dropout. Ocular discomfort symptoms were scored by ocular surface disease index (OSDI) questionnaire. RESULTS: 120 eyes of 120 patients (62 females, 58 males; mean age 73.85 years, range 47-91 years) were included. All patients had at least 1 abnormal finding, while 19 (15.8%; 95% CI [0.09-0.22]) had alterations of all parameters. In detail, 39 patients (32.5%; 95% CI [0.24-0.41]) had pathological TMH (mean 0,15 mm [0.03 SD]), 102 (85%; 95% CI [0.79-0.91]) had pathological NIKBUT (mean 3.64 s [2.63 SD]), 117 (97.5%; 95% CI [0.95-1]) had some degree of gland dropout (mean 1.62 [0.70 SD]), 78 patients (65%; 95% CI [0.56-0.74]) had pathological OSDI scores (mean 28.63 [15.08 SD]). Using TFOS DEWS II criteria, 66 patients (55%; 95% CI [0.42-0.60]) resulted affected by dry eye. CONCLUSIONS: This quick noninvasive screening documented the high prevalence of pathological ocular surface parameters in patients without risk factors or previous diagnosis of dry eye who are scheduled for cataract surgery.

Outcomes of low-level light therapy before and after cataract surgery for the prophylaxis of postoperative dry eye: a prospective randomised double-masked controlled clinical trial.

BACKGROUND: Despite increasing evidence shows that optimising ocular surface before cataract surgery is fundamental in patients with pre-existing dry eye disease (DED) to achieve the desired postoperative outcomes, the prophylactic treatment of healthy patients undergoing surgery aiming at preventing iatrogenic DED is worth investigating. METHODS: This was a prospective, interventional, randomised, controlled, double-masked clinical trial. Patients were randomly assigned 1:1 to receive either low-level light therapy (LLLT) or sham treatment (LLLT with a power output <30%). Patients underwent two treatment sessions: 7±2 days before cataract surgery (T0) and 7±2 days after (T1). Outcome measures evaluated 30±4 days after surgery (T2) included Ocular Surface Disease Index (OSDI) questionnaire, non-invasive break-up time (NIBUT), tear meniscus height, meibomian gland loss (MGL) and redness score. RESULTS: Out of 153 patients randomised to receive LLLT (n=73) or sham treatment (n=80), 131 (70 men, 61 women, mean age 73.53±7.29 years) completed regularly the study. Patients treated with LLLT had significantly lower OSDI scores compared with controls at T1 and T2 (respectively, 7.2±8.8 vs 14.8±13.0 and 9.0±9.0 vs 18.2±17.9; both p<0.001), higher NIBUT values at T2 (12.5±6.6 vs 9.0±7.8; p=0.007) and lower MGL Meiboscore values at T1 (1.59±0.70 vs 1.26±0.69; p=0.008). Unlike controls, patients treated with LLLT had significantly lower OSDI scores and higher NIBUT values at T2 compared with T0 (respectively, 9.0±9.0 vs 21.2±16.1; p<0.001 and 12.5±6.6 vs 9.7±7.2; p=0.007). CONCLUSION: Two sessions of LLLT performed before and after cataract surgery were effective in ameliorating tear film stability and ocular discomfort symptoms. TRIAL REGISTRATION NUMBER: NCT05754437.

Clinical Outcomes of Topical 0.1% Ciclosporin Cationic Emulsion Used on Label in Children with Vernal Keratoconjunctivitis.

INTRODUCTION: The purpose of this short article is to report the clinical outcomes of topical 0.1% ciclosporin cationic emulsion (CsA-CE) used on label in children with vernal keratoconjunctivitis (VKC). METHODS: In this prospective, non-comparative, observational study children affected by active severe VKC were treated for at least 12 months with topical 0.1% CsA-CE. The drug was instilled in both eyes 4 times daily. Data collected from medical charts for the baseline visit (T0) and 1-year follow-up visit (T1) included symptomatic score (0-15), clinical score (0-15), side effects, rescue therapy (need and total number of courses with 0.1% dexamethasone 4 times daily for 5 days), ocular complications and tolerability (visual analog scale [0-100]). RESULTS: Data from 25 children (20 boys, 5 girls; mean [± standard deviation] age 8.40 ± 2.54 years) were included in the study. Of the 25 patients, 23 (92%) used 0.1% CsA-CE eye drops as per label recommendations, including four patients who had prematurely stopped using topical galenic CsA due to side effects. Symptomatic and clinical scores decreased significantly after treatment, with the mean symptomatic score decreasing from 9.76 ± 1.27 at T0 to 3.80 ± 1.08 at T1, and the mean clinical score decreasing from 9.20 ± 1.32 at T0 to 3.44 ± 1.00 at T1; both P < 0.0001). Five patients (20%) required at least one course of rescue medication (mean 3.4 ± 4.8 courses/year). No patients experienced ocular complications during the study, and treatment tolerability was very high (mean score 89.40 ± 5.46). CONCLUSION: Our findings confirm that topical CsA-CE is an effective on-label option for children with VKC in the real-life setting. In our pediatric patient population, CsA-CE provided good clinical outcomes with a limited need for rescue medication, and it was well tolerated by almost all patients, including those who were intolerant to galenic formulations.

Low-Level Light Therapy Versus Intense Pulsed Light for the Treatment of Meibomian Gland Dysfunction: Preliminary Results From a Prospective Randomized Comparative Study.

PURPOSE: The purpose of this study was to evaluate and compare the safety and efficacy of low-level light therapy (LLLT) and intense pulsed light (IPL) for the treatment of meibomian gland dysfunction (MGD). METHODS: Forty eyes of 40 patients with MGD were randomized to receive either LLLT or IPL. Four weekly sessions of LLLT (MY MASK-E, Espansione Marketing S.p.A., Bologna, Italy) and IPL (Eye-light device, Espansione Marketing S.p.A., Bologna, Italy) were performed. The following parameters were evaluated before and 2 weeks after the last session for each treatment: Standard Patient Evaluation of Eye Dryness questionnaire, noninvasive break-up time, tear meniscus height, redness score, meiboscore, and meibomian gland loss. RESULTS: All patients completed regularly all the scheduled sessions, and no adverse events were reported in any of the groups. The Standard Patient Evaluation of Eye Dryness score significantly decreased after both LLLT and IPL (P < 0.001) although the improvement was significantly greater in the LLLT compared with the IPL group (-9.9 ± 3.2 vs. -6.75 ± 4.5; P = 0.014). Patients in the LLLT group showed a significantly higher increase in tear meniscus height compared with those in the IPL group (0.06 ± 0.10 mm vs. -0.01 ± 0.014; P = 0.040). In both groups, the noninvasive break-up time, redness score, meiboscore, and meibomian gland loss did not vary significantly after treatment (all P > 0.05). CONCLUSIONS: Both LLLT and IPL were safe and effective in improving ocular discomfort symptoms in patients with MGD; however, the former determined a greater improvement in symptoms and an improvement of tear volume.

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.

Preliminary Results of a Novel Standardized Technique of Femtosecond Laser-Assisted Deep Anterior Lamellar Keratoplasty for Keratoconus.

PURPOSE: To evaluate the feasibility and the initial outcomes of a novel standardized surgical technique of femtosecond laser- (FSL-) assisted big-bubble deep anterior lamellar keratoplasty (BBDALK) for eyes with keratoconus. METHODS: This prospective interventional case series included 11 consecutive FSL-assisted BBDALK procedures performed for the eyes with keratoconus from September 2019 to December 2019. The FSL was used to create (i) an intrastromal channel incision (1.7 mm in length, 4.6 mm in width, 80% depth, and cut energy of 1.70 µJ) and (ii) a 9.0 mm diameter circular lamellar side cut 65 µm above the endothelium (cut energy of 0.90 µJ) intersecting the intrastromal incision. In the operating room, a blunt dissector was used to open the intrastromal channel incision, through which a blunt spatula was inserted, tangentially advanced towards the center of the cornea, and replaced with a blunt cannula for pneumatic dissection. The subsequent surgical steps did not differ from the conventional technique. Main outcome measures were the success rate of pneumatic dissection and the percentage of intraoperative complications. RESULTS: Eleven eyes of 11 patients (6 males and 5 females; mean age: 34.54 ± 13.23 years) underwent FSL-assisted DALK. Using the FSL, both corneal incisions (lamellar side cut and intrastromal channel incision) were successfully created in all cases without the need for repeat docking or additional dissection. Pneumatic dissection with type 1 bubble formation succeeded in all 11 eyes (100%). DALK surgery was completed uneventfully in all cases. Descemet membrane perforation did not occur in any case, and no procedure was converted to penetrating keratoplasty. CONCLUSION: Using standardized FSL parameters for both incision design and cut energy in BBDALK surgery, pneumatic dissection can be achieved in a very high rate of cases with minimal risk of intraoperative complications.

Efficacy and Safety of Wet Wipes Containing Hy-Ter® Solution Compared with Standard Care for Bilateral Posterior Blepharitis: A Preliminary Randomized Controlled Study.

INTRODUCTION: A novel treatment for posterior blepharitis which involves the use of disposable wet wipes imbibed with a solution of terpinen-4-ol and hyaluronic acid (Hy-Ter®) as well as aloe, natural anti-inflammatories and antiseptics (Blephapad Combo; Novelty Technology Care, Milan, Italy) has been proposed. The aim of this study was to compare the efficacy and safety of treatment with Blephapad Combo with standard treatment. METHODS: We conducted 4-week, open-label, randomized controlled study with a closed sequential design at the Magna Graecia University of Catanzaro, Italy in which patients aged > 40 years with symmetrical bilateral posterior blepharitis were enrolled. Each eye represented a single experimental unit. Patients were randomly assigned using a computer-generated randomization list to apply a reusable heated compress to the eyelid of one eye before cleansing the eyelid with the Blephapad Combo wet wipe (Blephapad Combo treatment arm) or to use the standard treatment of applying a wet and warm gauze to the other eye (standard treatment arm), twice daily for 4 weeks. The primary endpoint was the percentage change from baseline to week 4 in meibomian gland dysfunction (MGD) grading scale scores. RESULTS: Eighteen patients (9 men; 9 women) with a mean (± standard deviation) age of 66.9 ± 9.03 years were included in the study. Compared with the eye receiving the standard treatment, treatment with Blephapad Combo appeared to improve the MGD total score after 4 weeks of treatment (mean change from baseline - 29.9 vs. - 38.5%). The assessment of the investigators was that in 11 patients the eye treated with Blephapad Combo showed greater benefit, in two patients the eye treated with the standard treatment showed greater benefit and in four patients there was no difference between treatments. Blephapad Combo was well tolerated, with no serious adverse events (AEs) reported. Minor ocular AEs were reported in 44.4 and 38.9% of patients in the Blephard Combo and standard treatment arms, respectively. CONCLUSIONS: Treatment with Blephapad Combo was more effective than the standard treatment in ameliorating MGD in patients with posterior blepharitis. Minor ocular AEs events were equally distributed between the two treatments arms. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03301844.

Results of viscobubble deep anterior lamellar keratoplasty after failure of pneumatic dissection.

AIM: To report the outcomes of bubble formation obtained by means of intrastromal injection of ophthalmic viscoelastic device (OVD) after failure of pneumatic dissection for deep anterior lamellar keratoplasty (DALK). METHODS: DALK was performed in 140 keratoconic eyes of 130 patients by injecting air and OVD only secondarily, after pneumatic dissection had failed; the bubble formation rates after air and OVD injection were recorded; complications, best spectacle-corrected visual acuity (BSCVA) and corneal tomographic parameters were evaluated 3 months, 6 months and 12 months postoperatively, as well as after complete suture removal. RESULTS: Air injection created a big bubble in 106/140 eyes (75.71%); OVD injection was not attempted in 4 eyes (perforation during cannula insertion n=2; air bubble burst n=2) and created a big bubble in 28 of the remaining 30 eyes (93.33%, 20% of the total). Manual dissection was required in 2/30 eyes (6.66%, 1.42% of the total) after failed OVD-assisted dissection.Deep folds, interface opacity and reduced BSCVA were noted in both eyes after failed OVD-assisted dissection. BSCVA was statistically better after pneumatic-assisted than after OVD-assisted dissection (P 0.01) only up to 3 months postoperatively; no statistically significant differences were recorded between the two techniques at later examinations. CONCLUSION: Intrastromal injection of OVD after failed pneumatic dissection increases considerably the success rate of bubble formation (from 75.71% to 95.71% in our series); however, when bubble formation fails, infiltration of OVD into the residual stroma makes manual dissection particularly challenging and causes severe interface haze resulting in poor visual outcomes.

Curcumin protects against NMDA-induced toxicity: a possible role for NR2A subunit.

PURPOSE: Curcumin, a phenolic compound extracted from the rhizome of Curcuma longa, was found to attenuate NMDA-induced excitotoxicity in primary retinal cultures. This study was conducted to further characterize curcumin neuroprotective ability and analyze its effects on NMDA receptor (NMDAr). METHODS: NMDAr modifications were analyzed in primary retinal cell cultures using immunocytochemistry, whole-cell patch-clamp recording and western blot analysis. Cell death was evaluated with the TUNEL assay in primary retinal and hippocampal cultures. Optical fluorometric recordings with Fura 2-AM were used to monitor [Ca(2+)](i). RESULTS: Curcumin dose- and time-dependently protected both retinal and hippocampal neurons against NMDA-induced cell death, confirming its anti-excitotoxic property. In primary retinal cultures, in line with the observed reduction of NMDA-induced [Ca(2+)](i) rise, whole-cell patch-clamp experiments showed that a higher percentage of retinal neurons responded to NMDA with low amplitude current after curcumin treatment. In parallel, curcumin induced an increase in NMDAr subunit type 2A (NR2A) level, with kinetics closely correlated to time-course of neuroprotection and decrease in [Ca(2+)](i). The relation between neuroprotection and NR2A level increase was also in line with the observation that curcumin neuroprotection required protein synthesis. Electrophysiology confirmed an increased activity of NR2A-containing NMDAr at the plasma membrane level. CONCLUSIONS: These results confirm the neuroprotective activity of curcumin against NMDA toxicity, possibly related to an increased level of NR2A, and encourage further studies for a possible therapeutic use of curcumin based on neuromodulation of NMDArs.

Biocompatibility assessment of liquid artificial vitreous replacements: relevance of in vitro studies.

The biocompatibility of liquid artificial vitreous replacements is generally assessed by performing tests in animal models before their clinical use, whereas in vitro experimentation is seldom carried out due to their physico-chemical characteristics. Since their introduction in vitreoretinal surgery, however, the use of some certified vitreous replacements has been discouraged after clinical trials, because of the occurrence of serious side effects. This observation suggests that the tests currently performed for biocompatibility assessment cannot fully guarantee their safety when they are used in humans. Here we review the available literature on in vitro biocompatibility testing of liquid artificial vitreous replacements and survey our own experience on the subject, obtained by using primary retinal cell cultures, seeded on micro-porous inserts. We suggest that in vitro biocompatibility assessment, conducted before experiments in animal models, could improve the required safety evaluation and decrease the risk of undesired side effects, as well as providing a beneficial reduction of animal experimentation.

Induction of apoptosis in rat retinal cell cultures by partially fluorinated alkanes.

PURPOSE: To test whether the partially fluorinated alkanes (PFAs) perfluorobutylbutane (O(44)), perfluorohexylethan (O(62)), and the oligomer OL(62HV), recently proposed as artificial vitreous replacements (AVRs), have pro-apoptotic effect in rat retinal cultures. DESIGN: Laboratory investigation. METHODS: Rat retinal cell cultures were seeded onto microporous inserts to study AVR-cell interaction without impairing cell survival. Cells were treated for 24 hours with O(62), O(44), and OL(62HV). Apoptosis was analyzed by transferase-mediated dUTP-biotin nick end-labeling assay and Hoechst stain. RESULTS: O(44) and O(62) did not affect structural organization and cell survival in retinal cell cultures; however, OL(62HV) induced increased apoptosis compared with control cultures. CONCLUSIONS: OL(62HV), a high-viscosity PFA, induces severe retinal damage in human eyes, although it successfully passed animal experimentation. Our in vitro study showed a remarkable pro-apoptotic effect of OL(62HV) and suggests that in vitro tests can contribute to AVR biocompatibility assessment.