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The purpose of this study is to characterize the ocular surface microbiota of patients with an anophthalmic cavity. An eNAT with 1 mL of Liquid Amies Medium was used to collect samples. Microbial DNA from anophthalmic socket and healthy fellow control eye samples was isolated and sequenced. Raw reads were analyzed with GAIA (v 2.02). The richness and Shannon alpha diversity metrics, as well as Bray-Curtis beta diversity and Wilcoxon signed-rank test values, were computed with R packages such as phyloseq, mia, or DESeq2 to allow for microbiome analysis. Principal coordinate analysis (PCoA) was performed using the function plotReducedDim from the R package scater. The different taxonomic profiles were described under the concept of eye community state type (ECST). The microbiomes of both eyes from 25 patients with an anophthalmic cavity were analyzed in this study. While the microbial communities of paired eyes from the same patients showed notable dissimilarity, no consistent patterns emerged when comparing healthy eyes to anophthalmic sockets. Alpha diversity values did not significantly differ between healthy eyes and anophthalmic socket samples, though there was considerable variability within each group. Notably, anophthalmic socket samples generally exhibited lower abundances of genera such as Staphylococcus , Enterococcus , Paenibacillus , and Sediminibacterium compared to their healthy counterparts. Microbial variability between healthy eyes and anophthalmic sockets may be due to anatomical differences. Further research is needed to determine whether patients without anophthalmic sockets exhibit similar microbiome patterns in both eyes.

Methods: Multicenter retrospective case series of nd:Yag laser fragmentation of LF in twenty eyes at different clinics discovered after cataract surgery performed through phacoemulsification and implant of intraocular lens (IOL)., Conclusion: Early nd:Yag laser procedure is a good option to use for retained lenticular fragments in the anterior chamber after cataract extraction, to reduce damages to the endothelium caused by the LF, to lower patient discomfort to re-enter surgery, to minimize costs of surgical re-intervention and to avoid possible inflammatory complications given by the retained fragments that may not be reabsorbed properly and may even present several years after primary surgery leading to damages to endothelium caused by the lenticular fragments and visual disturbances., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To investigate the reduction of the ocular surface bacterial load induced by 2 commercially available ophthalmic antiseptic formulations, povidone-iodine (PVI) 0.6% and chlorhexidine (CLX) 0.02%, before ocular surgery., Design: Randomized controlled trial., Methods: Seventy adult patients undergoing intraocular surgery (phacoemulsification) were randomized to receive in the index eye PVI (group A) 4 times a day for 3 days or CLX (group B) 4 times a day for 3 days before surgery. The untreated eye was used as control. A conjunctival swab was taken in both eyes before (T0) and after (T1) therapy. Microbial DNA was quantified with real-time polymerase chain reaction (PCR) analysis. The Mick algorithm was used to compare the abundance of each genus/genera against the distribution of abundances from the reference. At T1, patients filled a questionnaire to evaluate therapy-induced symptoms. Primary outcome was the reduction of bacterial DNA at T1 (microbial load), vs control arm, expressed as mean number of real-time PCR cycle times (CTs). Secondary outcomes were taxonomic composition, differential abundance, and therapy-induced ocular symptoms., Results: The T0-T1 difference in CT was significant in group B, but not in group A (mean [95% CI], 0.99 [0.33] vs 0.26 [0.15], P < .001, and 0.65 [0.3] vs 0.45 [0.41], P = .09, respectively). The taxonomic composition, alpha, and beta diversity remained consistent at all time points in both groups. The rate of patients reporting therapy-induced ocular symptoms and the mean discomfort grade were greater in group A than in group B (97% vs 26% and 4.97±2.48 vs 0.66±1.53, respectively)., Conclusions: Compared with PVI 0.6%, CLX 0.02% induced a greater reduction of ocular surface bacterial load, with no significant alterations of the taxonomic composition. Moreover, CLX was better tolerated than PVI., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose : To characterize microbial keratitis diversity utilizing species richness and Shannon Diversity Index. Methods : Corneal impression membrane was used to collect samples. All swabs were processed and analyzed by Biolab Laboratory (level V-SSN Excellence: ISO 9001:2015), Biolab Srl (Ascoli Piceno, Italy). DNA extraction, library preparation, and sequencing were performed in all samples. After sequencing, low-quality and polyclonal sequences were filtered out by the Ion software. At this point, we employed Kraken2 for microbial community analysis in keratitis samples. Nuclease-free water and all the reagents included in the experiment were used as a negative control. The primary outcome was the reduction in bacterial DNA (microbial load) at T1, expressed as a percentage of the baseline value (T0). Richness and Shannon alpha diversity metrics, along with Bray-Curtis beta diversity values, were calculated using the phyloseq package in R. Principal coordinate analysis was also conducted to interpret these metrics. Results : 19 samples were included in the study. The results exhibited a motley species richness, with the highest recorded value surpassing 800 species. Most of the samples displayed richness values ranging broadly from under 200 to around 600, indicating considerable variability in species count among the keratitis samples. Conclusions: A significant presence of both typical and atypical bacterial phyla in keratitis infections, underlining the complexity of the disease's microbial etiology.

Background: To evaluate the effects of 10% GlicoPro tear substitute therapy in patients with severe dry eye disease (DED). Methods: In this prospective longitudinal study, 30 individuals receiving 10% GlicoPro four times daily for DED were evaluated. The ocular surface disease index (OSDI) questionnaire, average non-invasive break-up time (A-NIBUT), non-anesthetic and anesthetic corneal esthesiometry (CE), ocular pain, and the presence of conjunctivochalasis (CCH) were used as clinical endpoints. Treatment compliance using dosing diaries and AEs was assessed. Results: A significant improvement was observed in the clinical endpoints: the ΔOSDI questionnaire was -39.27 ± 13.22 [-65 to -15] points, ΔA-NIBUT was 3.10 ± 1.31 [1 to 5] s, Δnon-anesthetic CE was 14 ± 6.35 [5 to 25] mm, and Δanesthetic CE was 13 ± 5.35 [5 to 20] mm ( p < 0.001 for all comparisons). Ocular pain was reduced in 92.5% of the patients at the end of the follow-up. However, there was no change in the presence of CCH. In addition, all the patients were fully compliant with the dosing and no AEs related to the use of the 10% GlicoPro tear substitute were reported. Conclusions: The 10% GlicoPro tear substitute has the potential to achieve beneficial effects in ocular surface treatments.

Introduction: Lid-parallel conjunctival folds (LIPCOF) and conjunctivochalasis (CCH) are similar conditions that seem to be related to dry eye severity. In addition, there is a lack of studies on the topic of LIPCOF and CCH on dry eye symptoms in non-contact lens and contact lens (CL) wearers. Therefore, the aim of this study is to review the relationship of LIPCOF and CCH with dry eye symptoms in non-CL and CL wearers, as well as to report the treatment of dry eye disease (DED) in non-CL and CL wearers who present LIPCOF or CCH., Methods: A literature review of full-length original studies in two databases, PubMed and Scopus, was performed. The search period included observational studies in humans published between April 21, 2009 and March 20, 2023., Results: A total of 26 studies were included. The studies suggest that LIPCOF and CCH are significantly related to dry eye symptoms in non-CL and CL wearers. However, the impact of CL wear on LIPCOF and CCH may be complex and may vary depending on individual factors such as lens type, lens care regimen, and pre-existing ocular conditions. Regarding LIPCOF management, tear substitutes seem to significantly reduce LIPCOF and dry eye symptoms in non-CL wearers, while vectored thermal pulsation (VTP) and microblepharoexfoliation (MBE) are suggested as promising treatment for LIPCOF and dry eye symptoms in CL wearers. Regarding CCH management, surgical interventions may be effective in reducing CCH when medical treatments have no response. In addition, an ocular examination by slit lamp is necessary to distinguish both conditions., Conclusions: Tear substitutes, VTP, MBE, and fitting CLs with low coefficient of friction (CoF) seem to reduce and prevent LIPCOF. However, surgical treatment options seem to be more effective in the complete elimination of CCH. An adequate evaluation and differentiation between LIPCOF and CCH are important, and they should be considered by practitioners in managing dry eye symptoms in non-CL and CL wearers., (© 2024. The Author(s).)

Purpose: The aim of this study was to report the 12 to 96 months results of a tissue-preservation algorithm based on ray-tracing-guided transepithelial excimer laser central corneal ablation (RT t-PRK) combined with individualized pachymetry-guided accelerated crosslinking (M nomogram ACXL) in young adult patients with stable keratoconus (KC)., Methods: This was a prospective interventional study including 38 eyes of 38 young adult patients (stage II KC) with a mean age of 35 years (range 26-46 years) who underwent simultaneous RT with t-PRK plus pachymetry-based ACXL in the worst eye. The treatments were performed using the iViS Suite iRES Excimer Laser (Ligi, Taranto, Italy). Ray-tracing-guided treatments were planned using the customized interactive programmed transepithelial ablation (CIPTA) 2 web software and diagnostic data were assessed by the Precisio 2 tomographer (Ligi, Taranto, Italy) and Sirius tomographer (C.S.O., Florence, Italy). The main outcome measures included uncorrected distance visual acuity, best spectacle-corrected visual acuity, Kmax, high-order aberrations, minimum corneal thickness, and posterior elevation, with a mean follow-up of 52 months (range 12-96 m)., Results: The mean UDVA improved + 3.5 ±1.28 Snellen lines (SL); 38% gained ≥ 4 ±1.34 SLs, 35% ≥ 3 ±1.21 SLs, 22% ≥ 2 ±1.12 SLs, and 5% ≥ 1 ±0.75 SLs. The mean best spectacle-corrected visual acuity increased by + 4.3 ±1.3 SL. Sixty-eight percent gained ≥ 4 ±0.88 SLs and 30% ≥ 3 ±0.78 SL. No SLs were lost., Conclusions: RT t-PRK plus ACXL significantly improved the quality of vision in patients with KC, preventing overcorrection and minimizing tissue consumption., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: To evaluate the efficacy and safety of Quantum Molecular Resonance (QMR) treatment in patients with severe dry eye disease (DED), as well as its effects on aqueous-deficient (ADDE), evaporative (EDE), and mixed (MDE) dry eye., Methods: In this prospective, interventional study, 81 patients were randomly allocated to received four treatment sessions of QMR at 1-week intervals (Rexon-Eye ® , Resono Ophthalmic, Trieste, Italy) (QRM group) or tear substitute four times daily, containing 0.15% sodium hyaluronate and 3% trehalose (Thealoz Duo ® , Thea Pharma, France) (SH-TH group). Outcome measures included ocular surface disease index (OSDI) questionnaire, tear meniscus height (TMH), tear breakup time (TBUT), non-invasive breakup time (NIBUT), corneal fluorescein staining (CFS), lipid layer thickness (LLT), tear film osmolarity (OSM), and meibomian gland dysfunction (MGD) grade, which were assessed at baseline and 1-month and 3-month follow-up., Results: The QMR group achieved better improvements than the SH-TH group in OSDI and SANDE questionnaires, NIBUT, LLT, and CFS. The mean differences between the groups were as follows: OSDI (- 12.4 ± 0.25 points, P = 0.01), SANDE (10.6 ± 1.7 points, P = 0.01), NIBUT (2 ± 0.25 s, P = 0.01), LLT (18.7 ± 0.7 nm, P = 0.01), and CFS (1.2 ± 0.1 points, P = 0.02). In subgroups analysis, QMR treatment demonstrated a beneficial role to improve DED symptoms and signs in ADDE, EDE, and MDE., Conclusion: QMR is an effective and well-tolerated treatment that seems to improve DED symptoms and signs in patients with severe DED. However, further studies are needed to confirm this., Trial Registration: ClinicalTrials.gov identifier NCT06119386., (© 2023. The Author(s).)

Purpose: To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED)., Methods: A systematic review that included full-length randomized controlled studies (RCTs), as well as post hoc analyses of RCTs reporting new findings on OC-01 VNS treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included studies published between December 2021 and September 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected., Results: A total of 8 studies were included in this systematic review. OC-01 VNS treatment achieved higher improvement than vehicle in all reported variables. The mean differences between both groups were in favor of OC-01 VNS treatment and were as follow: eye dryness score base on a visual analogue scale (EDS-VAS) of -7.5 ± 2.2 points [-11.6 to -5.6], Schirmer test (ST) with anesthesia of 6.6 ± 2.3 mm [4.9 to 11.8] and total corneal fluorescein staining (tCFS) of -1.2 ± 0.01 points [-1.2 to -1.1]. Similar improvements were reported with OC-01 VNS 0.03 mg and 0.06 mg. Adverse events (AEs) were 15.5 ± 19.4 % [-13 to 80.5] higher in the OC-01 VNS group with an overall adherence > 93 %., Conclusions: OC-01 VNS improves dry eye symptoms and signs with a satisfactory tolerability. Therefore, OC-01 VNS seems to be a safe and effective treatment that could be recommended in patients with DED. This new treatment could be particularly useful in those patients who have difficulties with the administration of traditional topical therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this study was to check the efficacy and safety of a novel tear substitute containing hyaluronic acid and low-dose hydrocortisone in the treatment of moderate dry eye disease. Methods: In this prospective randomized study, 38 patients with moderate dry eye disease were divided into two treatment groups: Group 1 received one drop of 0.2% sodium hyaluronate and 0.001% hydrocortisone four times daily for 3 months, while Group 2 received 0.15% sodium hyaluronate and 3% trehalose at the same dosage. OSDI and SANDE questionnaires, Non-Invasive Break-Up time (NIBUT), Tear Meniscus Height (TMH), meibography, Lipid Layer Thickness (LLT), Tear Break-Up Time (TBUT), Corneal Staining Score (CFS), and Intraocular Pressure (IOP) were evaluated at baseline and after 1, 2, and 3 months of treatment. Results: During the treatment period, Group 1 showed statistically significant improvement in OSDI score ( p = 0.002), SANDE score ( p = 0.01), NIBUT ( p < 0.0001), LLT ( p < 0.0001), TBUT ( p = 0.01), and CFS ( p = 0.02). In Group 2, significant improvement was observed only in the TBUT score ( p < 0.05). Comparison of the two groups showed that NIBUT and LLT were significantly different at the end of treatment ( p = 0.001 for both comparisons), with more favorable results for sodium hyaluronate and hydrocortisone than for sodium hyaluronate and trehalose. No significant variations in intraocular pressure were observed in either group during the treatment period ( p > 0.05). Conclusions : The study confirms that a 3-months treatment with hyaluronic acid 0.2% in combination with low-dose hydrocortisone 0.001% improves the signs and symptoms of moderate DED and that a low-dosage 0.001% hydrocortisone can be helpful in preventing the progression to chronic stages of DED.

Purpose: To compare corneal densitometry in a consecutive series of 52 endothelial keratoplasties (DMEK/DSAEK) using a Scheimpflug-based device after six months of follow-up., Methods: Corneal densitometry (CD) values of 102 eyes were divided into three main groups: 33 DMEKs, 19 DSAEKs, and 50 healthy eyes without previous ocular surgery. The CD values were then analyzed and compared between the groups. We measured three main layers in depth and four different concentric zones at 1, 3, and 6 months postoperatively., Results: In the DMEK group, total CD significantly decreased from 38.02 ± 10.21 grayscale units (GSU) to 31.13 ± 9.25 GSU (P < 0.01) between the first and the sixth month postoperative. In the DSAEK group, we found significant changes only between the first and three months after surgery (from 42.62 ± 9.31 GSU to 38.71 ± 10.53 GSU (P < 0.01). Regarding the concentric zones, CD in the DMEK group significantly decreased in the central zone from 33.55 ± 12.07 GSU to 30.63 ± 10.15 GSU (P < 0.01) and significantly increased in the periphery from 30.63 ± 10.15 GSU to 36.72 ± 9.37 GSU, (P < 0.01). The DSAEK group showed no changes in the central zone (from 36.91 ± 13.80 GSU to 36.14 ± 11.47 GSU, P = 0.52) and CD significantly increased in the periphery (41.91 ± 9.28 GSU, P < 0.01)., Conclusion: When comparing CD values in DMEK versus DSAEK, we found no differences by layers or at central-paracentral concentric zones, although CD differences in the peripheral zones were statistically significant. This finding may be attributed to the thicker graft at periphery with a delayed clearance and less anatomical interphase in DSAEK., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: We aimed to evaluate the effects of 0.3% carboxymethylcellulose (CMC) tear substitute treatment in dry eye disease (DED), as well as treatment compliance and adverse events (AEs)., Methods: In this prospective, longitudinal study, a total of 30 eyes receiving 0.3% CMC tear substitute four times daily for DED were evaluated. Clinical endpoints included an ocular surface disease index (OSDI) questionnaire, average non-invasive tear film break-up time (A-NIBUT), lipid layer thickness (LLT), and a Schirmer test with anesthesia (ST). Treatment compliance and AEs were also assessed. All evaluations were performed at 2, 4, and 12 weeks of follow-up., Results: At the end of the follow-up, significant improvement was observed in all clinical endpoints with the following mean values: ΔOSDI questionnaire of -22.53 ± 14.68 points, ΔA-NIBUT of 4.81 ± 2.88 s, ΔLLT of 5.63 ± 6.53 nm, and ΔST of 2.8 ± 2.1 mm ( p < 0.001 for all comparisons). Although repeated measures analysis showed that all clinical endpoints presented statistically significant differences ( p < 0.001 for all comparisons LLT Baseline -LLT 2-weeks ( p = 0.460) and LLT 4-weeks -LLT 12-weeks ( p = 0.071) were the only pairs of measures that reported non-statistically significant differences). In addition, treatment compliance was 94.3 ± 5.2% and transient AEs related to the use of 0.3% CMC tear substitute were reported., Conclusions: 0.3% CMC tear substitute treatment seems to achieve beneficial effects on the OSDI questionnaire, A-NIBUT, LLT, and ST. However, further studies at this concentration are needed to confirm these results.

Background: To compare corneal densitometry (CD) patterns at the graft-host interface between Descemet Membrane Endothelial Keratoplasty (DMEK) and Descemet Stripping Automated Endothelial Keratoplasty (DSAEK). Corneal densitometry is a quantitative assessment that objectively evaluates corneal clarity and optical quality by measuring the light backscatter from the cornea., Methods: Fifty-one eyes that received DMEK or DSAEK surgery for corneal endothelium dysfunction were evaluated. The primary endpoint included CD patterns at the graft-host interface, which were assessed by the Pentacam HR device at the center point of the corneal horizontal meridian (CD central ), and at six points on the central circumference of the cornea (with a total diameter of 4 mm) (CD I,II,III,IV,V,VI ). Secondary endpoints included the best-corrected distance visual acuity (BCDVA), central corneal thickness (CCT), and graft thickness (GT). All of the evaluations were performed at follow-up appointments one, three, six and twelve months after the procedure., Results: DMEK showed a significant overall CD reduction of -7.9 ± 8.5 grayscale unit (GSU) compared to DSAEK ( p < 0.001). In addition, the DMEK group showed significantly lower CD Central,I,II,III,IV,V,VI values at follow-up appointments one, three, six and twelve months after the procedure compared to the DSAEK group ( p < 0.001). BCDVA, CCT and GT were in favor of the DMEK group with a mean value of 0.39 ± 0.35 LogMar, 552.2 ± 71.1 µm and 11.03 ± 1.4 µm, respectively ( p < 0.001)., Conclusions: CD patterns at the graft-host interface seem to be different depending on the endothelial keratoplasty procedure. This provides specific insight into CD changes in this critical region of surgery, which may provide a better understanding of the postoperative evolution of these patients.

In the field of Ophthalmology, the mNGS 16S rRNA sequencing method of studying the microbiota and ocular microbiome is gaining more and more weight in the scientific community. This study aims to characterize the ocular microbiota of patients diagnosed with keratoconus who have not undergone any prior surgical treatment using the mNGS 16S rRNA sequencing method. Samples of naïve keratoconus patients were collected with an eNAT with 1 mL of Liquid Amies Medium (Copan Brescia, Italy), and DNA was extracted and analyzed with 16S NGS. The microbiota analysis showed a relative abundance of microorganisms at the phylum level in each sample collected from 38 patients with KC and 167 healthy controls. A comparison between healthy control and keratoconus samples identified two genera unique to keratoconus, Pelomonas and Ralstonia. Our findings suggest that alterations in the microbiota may play a role in the complex scenario of KC development.

During infectious keratitis, the production of collagenolytic and inflammatory substances, along with increased corneal matrix metalloproteinase (MMP) activity, induces the degradation of corneal collagen and may cause postkeratitis complications, such as opacity, thinning, and corneal perforation. MMPs, especially MMP-2 and MMP-9, are overexpressed in infectious keratitis and sustained over time by inflammatory and nonmicrobial mechanisms. The high MMP levels are correlated with excessive corneal destruction in bacterial, herpetic, fungal, and acanthamoeba infections. Nonspecific treatments, such as tetracyclines, particularly doxycycline, or corticosteroids, are used as adjuvants to antimicrobials to alleviate the disproportionate degradation and inflammation of the corneal layers caused by corneal MMPs and decrease the recruitment and infiltration of inflammatory cells. Treatments showing inhibition of specific MMPs (Galardin, ZHAWOC7726), interfering with pro-MMP activation (EDTA, ascorbic acid), or showing anticytokine effect (epigallocatechin-2-gallate, TRAM-34) have been reported. Other treatments show a direct action over corneal collagen structure such as corneal cross-linking or have been associated with reduction of MMP levels such as amniotic membrane grafting. Although the use of these drugs has been shown in studies to be effective in controlling inflammation, especially in experimental ones, robust studies are still needed based on randomized and randomized clinical trials to demonstrate their potential effect as adjuvants in the management of infectious keratitis., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To report a case of epithelial downgrowth after penetrating keratoplasty., Case Description: A 58-year-old man presented with graft rejection in his three-month-old, repeat penetrating keratoplasty. Examination revealed centripetal opacification of the posterior cornea due to deep epithelization. He had new retro-corneal membranes and anterior uveitis. Specular microscopy and anterior segment optical coherence tomography were performed, and a clinical diagnosis of epithelial downgrowth was made. The patient had intracameral injections with 5-fluorouracil (5FU) and achieved resolution of intraocular findings after treatment., Conclusions: Epithelial downgrowth is an uncommon complication of penetrating keratoplasty. It affects the patients' visual acuity and graft survival. Clinical observation is preferred in severe cases due to the high risk of intraocular damage; intracameral 5FU promises to be a good option in these cases.

Purpose: To evaluate the microbiota of culture negative Corneal Impression Membrane (CIM) microbial keratitis samples with the use of shotgun metagenomics analysis., Methods: DNA of microbial keratitis samples were collected with CIM and extracted using the MasterPure™ Complete DNA and RNA Purification Kit (Epicentre). DNA was fragmented by sonication into fragments of 300 to 400 base pairs (bp) using Bioruptor® (Diagenode, Belgium) and then used as a template for library preparation. DNA libraries were sequenced on Illumina® HiSeq2500. The resulting reads were quality controlled, trimmed and mapped against the human reference genome. The unmapped reads were taxonomically classified using the Kraken software., Results: 18 microbial keratitis samples were included in the study. Brevundimonas diminuta was found in 5 samples while 6 samples showed the presence of viral infections. Cutibacterium acnes , Staphylococcus aureus , Moraxella lacunata and Pseudomonas alcaligenes were also identified as the presumed putative cause of the infection in 7 samples., Conclusions: Shotgun sequencing can be used as a diagnostic tool in microbial keratitis samples. This diagnostic method expands the available tests to diagnose eye infections and could be clinically significant in culture negative samples.

Purpose: The aim of this study was to evaluate the feasibility of Descemet membrane endothelial keratoplasty (DMEK) tissue preparation using a glasses-assisted 3-dimensional (3D) display system and to compare it with a conventional surgical microscope., Methods: Healthy pairs of human corneas suitable for penetrating keratoplasty surgery were selected for this study. The tissues were randomly divided into 2 groups. Each pair of corneas had 1 cornea (group 1) prepared with NGENUITY (Alcon) with a 5-second staining time with vision blue, and the fellow cornea (group 2) was prepared using a OPMI Lumera 700 surgical microscope (Carl Zeiss Meditec, Jena, Germany) with a 30-second staining time. DMEK graft preparation time, speed of stripping, graft width, and endothelial cell loss were evaluated., Results: Twenty-eight pairs of corneas were included in this study. The graft preparation time was significantly higher in the 3D group than in the conventional group (498 ± 147 vs. 418 ± 85 seconds, P value = 0.031). The mean speed of stripping was 0.59 ± 0.081 mm/s in group 1 and 0.089 ± 0.005 mm/s in group 2 ( P value = 0.024). The mean endothelial cell density in group 1 and group 2 before tissue preparation was 2162 ± 115.21 and 2153 ± 122.45, respectively ( P value > 0.1). After tissue preparation, the endothelial cell density reduced to 1911 ± 150.72 in group 1 and 1998 ± 90.72 in group 2 ( P value = P value > 0.05). The graft width was 5.05 ± 0.71 mm in group 1 and 4.92 ± 0.23 mm in group 2 ( P value > 0.05)., Conclusions: DMEK tissue preparation with 3D display system NGENUITY is feasible with a slightly increased preparation time. The improved visualization allows a reduced staining time that could be beneficial for eye banks because it may reduce the toxic effect of staining colorants., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To report the effectiveness of the surgical procedure of the tarsoconjunctival flap (FTC) in patients with severe ocular surface impairment refractory to previous conventional treatments., Methods: A retrospective, noncomparative, consecutive case series., Results: Pillar tarsoconjunctival flap (PTCF) was performed in eight eyes of eight patients. Three patients had neurotrophic corneal ulcer (NCU), three had exposure keratopathy and two had corneal melting. Seven of them had satisfactory postoperative results, showing total corneal re-epithelialization that lasted throughout the postoperative follow-up (mean 10.33 ± 2.65 months [SD], range 6 to 12 months). Mean time for the re-epithelization was 11.28 ± 8.97 days [SD] (range 4 to 30 days)., Conclusion: This study suggest PTCF is a valid alternative to tarsorrhaphy in cases of persistent epithelial defect (PED) or NCU resistant to conventional treatments. Notwithstanding, prospective comparative trials comparing PTFC with conventional and/or novel therapies in PED or NCU are needed to corroborate these findings.

Purpose: This study aims to explore and characterize healthy eye microbiota., Methods: Healthy subjects older than 18 years were selected for this descriptive cross-sectional study. Samples were collected with an eSwab with 1 mL of Liquid Amies Medium (Copan Brescia, Italy). Following DNA extraction, libraries preparation, and amplification, PCR products were purified and end-repaired for barcode ligation. Libraries were pooled to a final concentration of 26 pM. Template preparation was performed with Ion Chef according to Ion 510, Ion 520, and Ion 530 Kit-Chef protocol. Sequencing of the amplicon libraries was carried out on a 520 or 530 chip using the Ion Torrent S5 system (Thermo Fisher; Waltham, MA, USA). Raw reads were analyzed with GAIA (v 2.02)., Results: Healthy eye microbiota is a low-diversity microbiome. The vast majority of the 137 analyzed samples were highly enriched with Staphylococcus , whereas only in a few of them, other genera such as Bacillus, Pseudomonas, and Corynebacterium predominate. We found an average of 88 genera with an average Shannon index of 0.65., Conclusion: We identified nine different ECSTs. A better understanding of healthy eye microbiota has the potential to improve disease diagnosis and personalized regimens to promote health.

Metagenomics Next-Generation Sequencing can provide taxonomic and functional profiles of microbial keratitis communities without the need to culture infected corneal samples. We share our experience on a case with negative culture but positive metagenomic results.

Pseudopterygium is a non-progressive conjunctival adhesion to the peripheral cornea secondary to a corneal-limbus damage. According to the literature, the main etiology is a previous eye trauma. Nevertheless, this could be biased by the existence of other underdiagnosed causes of pseudopterygium, some of which may have severe consequences for the integrity of the eye and patient's life. This comprehensive literature review was performed based on a search on the PubMed and Google Scholar databases of relevant pseudopterygium published papers according to our current knowledge and seeks to gather the existing evidence about its diverse etiologies and clinical features, as well as to propose a diagnostic algorithm to simplify its correct approach.

Purpose: To assess the outcome of isolated Bowman's layer transplantation (BLT) in advanced keratoconus in the patients not suitable for ultra violet cross-linking and intra stromal corneal ring segments., Study Design: Nonrandomized Quasi-Experimental., Materials and Methods: Mid corneal stromal dissection followed by implantation of manually isolated bowman layer from a donor into the recipient stromal pocket was performed in the Department of Ophthalmology Khyber Teaching Hospital Peshawar from September 2018 to October 2018 and followed up over 18 months., Results: Eleven eyes of 11 patients, 8 male and 3 female within the age range of 7-28 years with progressive keratoconus went under BLT All keratometry values decreased after surgery. Mean anterior pre-operative SimK changed from 69.05 ± 10.85 D to 61.14 ± 6.23 D at 18 months post-operatively (P = 0.005). Means pre-operative Kmax value decreased from 77.24 ± 7.58 D to 71.07 ± 5.37 D at 18 months post-operatively (p = 0.060). The mean pre-operative posterior keratometry value changed from - 10.03 ± 0.88 to - 8.96 ± 1.06 D at 18 months post-operatively (P = 0.002). Mean pre-operative thinnest corneal thickness increased from 281.64 ± 196.86 um to 355.27 ± 19.17 um at 18th months post-operatively (P = 0.001). Pachymetry p-value pre-operative to 18 months (P = 0.001) was statistically significant. Mean anterior SimK at 6 months post-operatively, 60.55 ± 5.56D changed to 61.14 ± 6.23D at 18 months post-operatively (P = 0.000), Kmax at 6 months postoperative 71.60 ± 5.01 D changed to 71.07 ± 5.37 D at 18 months post-operatively (P = 0.008). Both anterior K values at 6 months and 18 months post-operatively showed less significant change, and the same was true for Kmax data at 6 months and 18 months post-operatively. P-values at 6 months to 18 months post-operatively for cornea back data remained (P = 0.001) unchanged. No complications were observed intra-operatively or post-operatively., Conclusion: Bowman layer transplantation is a unique surgical treatment for advanced keratoconus to stabilize progressive ectasia with fewer complications avoiding the need for penetrating or deep anterior lamellar keratoplasty., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

This review discusses the role of opioids in the corneal surface and the different pathways and therapeutic methods of management. A literature review was performed using PubMed database. For the database search, the main searching words "opioid" and "topical opioid treatment" were used with the descriptors "cornea", "ocular surface", "neuropathic corneal pain", "corneal sensitivity" and "naltrexone"; original scientific articles and reviews were included to achieve the purpose of the review. The endogenous opioid system has relevant functions in the organism, and in daily use, opioids are used as painkillers. However, these drugs may be employed for other indications as opioid pathways have a wide spectrum. The corneal surface for topical treatment is easily accessible, hence sparing the side effects of systemic opioids. Instillation of opioid antagonist substances, such as naltrexone, increases corneal healing rates and stimulates the division of corneal epithelium cells without deleterious effects. The natural modulation of endogenous opioids controls different forms of pain, including inflammatory and neuropathic pain, both in the ocular surface and in the central nervous system. There are diverse methods in controlling pain using opioids, especially in refractory forms. This review attempts to collect the literature about corneal surface and opioid pathways to provide an overview image and a possible direction of the news treatments.

Purpose: To measure the effects of Autologous serum (AS), Allogeneic Serum (HS) and Umbilical Cord serum (CS) eye drops in severe dry eye disease (DES), as well as to characterize and quantify several molecules in the three sera (albumin, fibronectin; Vitamin A and E; IgG, IgA and IgM; Transforming growth factor β; Epithelial growth factor)., Methods: Randomized, double-blind, single-centre, three-arm (AS, HS and CS) clinical trial. Sixty-three subjects were included with severe DES, 21 in each arm of the study. Visual acuity, Schirmer test, Breakup time (BUT), lissamine green, fluorescein staining measurements and a questionnaire were performed prior to treatment, and after one-month and three-month follow-up., Results: There was a significant main effect of time on visual acuities, Schirmer and BUT tests and fluorescein and lissamine green staining measurements and questionnaire scores (p = 0.015, p = 0.002, p < 0.001, p < 0.001, p = 0.031 and p < 0.001, respectively), although there was no significant interaction between time and serum type, nor between serum type and the test performed. Regarding the concentration of molecules, in our study AS contained significantly higher concentrations of IgA, IgG and fibronectin whereas HS contained significantly higher concentration of IgM, vitamins A and E, TGF and albumin. Contrary to previous reports, CS did not show higher concentration of any of the molecules analysed., Conclusions and Relevance: The three sera were effective in the treatment of severe DES. CS did not contain a higher proportion of molecules compared to AS/HS. More research is needed to assess the effect of AS in patients with DES and autoimmune diseases., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To analyze astigmatism axis changes after tropicamide and phenylephrine combined instillation., Method: One hundred and thirty-one eyes from 66 patients enrolled this cross-sectional study. An extensive ocular examination was carried out prior to tropicamide and phenylephrine instillation. Power and axis value from flat, steep, and mean keratometry were calculated using an Auto Kerato-Refractometer (AKR). Later, topography and tomography maps were evaluated with Pentacam HR® (Oculus, Wetzlar, Germany). Subsequently, a single drop of tropicamide 1% and phenylephrine hydrochloride 10% were instilled twice, with a five-minute gap between each instillation. After 30 minutes, the AKR and Pentacam HR® tests were repeated., Results: Incyclotorsion was found in 59 eyes (45.1%) and mean absolute incyclotorsion change was 3.91 ± 3.62 degrees (0.10 to 14.20). Excyclotorsion was found in 72 eyes (54.9%) and mean excyclotorsion change was 4.99 ± 5.94 degrees (0.20 to 36.20). We observed that 74.6% and 68.1% of eyes experienced incyclotorsion and excyclotorsion within 0 to 5 degrees, respectively. Fewer patients experienced incyclotorsion and excyclotorsion changes within 5 to 10 degrees, precisely 11.8% and 19.4%, respectively. Eyes that experienced over 10 degrees of incyclotorsion and excyclotorsion were 13.6% and 12.5%, respectively., Conclusion: Astigmatism axis could change after combined tropicamide and phenylephrine instillation. Reference axis marking in astigmatism correction surgery should be performed under the same circumstances as the astigmatism axis has been measured.

Purpose: To review all case series of refractive corneal inlay implantation: Flexivue (Presbia, Netherlands), Invue (BioVision, Brügg, Switzerland) and Icolens (Neoptics, Hünenberg, Switzerland) performed in presbyopia patients and to evaluate the reported visual outcomes. In addition, our aim is to provide assessment for complications and to report the satisfaction rates., Methods: PubMed, Web of Science and Scopus databases were consulted using "refractive corneal inlay", "Flexivue Inlay", "Invue Inlay" and "Icolens inlay" as keywords. 147 articles were found, and they were assessed considering the inclusion and exclusion criteria. After filtering, this systemic review included ten articles, published between 2011 and 2020., Results: 308 eyes from 308 participants were enrolled in this systematic review. Mean maximum follow-up was 13.9 months. Nine of the ten case series included used femtosecond laser for the corneal pocket creation. Mean pocket depth was 293.75 µm. 77.5% of the eyes reported a postoperative uncorrected near visual acuity of 20/32 or better, and 19.20% of the inlay-implanted eyes achieved an uncorrected distance visual acuity of 20/20 or better. The most prominent complications were halos, pain, photophobia, and poor distance visual acuity. 27 eyes (8.7%) had to be explanted due to complications, such as near-distance spectacle dependence or blurred distance vision., Conclusion: Refractive corneal inlay outcomes demonstrated high efficacy, safety, and satisfaction rates. Furthermore, it is a reversible technique. However, the findings must be viewed with caution due potential conflict of interest. Further research with higher sample size is needed to validate these findings., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The corneal endothelium has a crucial role in maintaining a clear and healthy cornea. Corneal endothelial cell loss occurs naturally with age; however, a diagnosis of glaucoma and surgical intervention for glaucoma can exacerbate a decline in cell number and impairment in morphology. In glaucoma, the mechanisms for this are not well understood and this accelerated cell loss can result in corneal decompensation. Given the high prevalence of glaucoma worldwide, this review aims to explore the abnormalities observed in the corneal endothelium in differing glaucoma phenotypes and glaucoma therapies (medical or surgical including with new generation microinvasive glaucoma surgeries). Descemet membrane endothelial keratoplasty (DMEK) is increasingly being used to manage corneal endothelial failure for glaucoma patients and we aim to review the recent literature evaluating the use of this technique in this clinical scenario., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Neeru A Vallabh et al.)

Purpose: To evaluate anterior segment optical coherence tomography (AS-OCT) to detect the wound healing process as per monitoring the effectiveness of cenegermin to treat moderate to severe neurotrophic keratoplasty. Methods: A retrospective chart review was realized to identify patients treated with cenegermin at the Clinica Oculistica, University of Genoa, Italy. All patients underwent careful examinations at baseline and follow-up visits. AS-OCT scans centered on the minimum corneal thickness (CT) area were always performed. We compared findings of AS-OCT with the findings from the slit-lamp examination. A linear regression analysis was used to evaluate factors associated with corneal healing. A further analysis, including a control group treated with 50% autologous serum (AS), was done to investigate and compare the efficacy of cenegermin. Results: Data from 16 eyes were studied. The average patients' age was 60.9 ± 21.1 years; five (31.2%) eyes experienced persistent epithelial defect and 11 (68.8%) eyes had neurotrophic corneal ulcer. The average reepithelialization time was 3.9 ± 0.5 weeks in the cenegermin group versus 5.9 ± 1.9 weeks in the AS group ( p < 0.01). The AS-OCT scans revealed an average CT at the thinnest point of 276.3 ± 74.1 μm before treatment with an average increase of 176.5 ± 60.3 μm at the end of the cenegermin treatment (B = -0.15; p = 0.035). The AS-OCT percentage increase in corneal thickness between the two groups was statistically significant ( p < 0.02). Conclusion: Understanding the cascade of events involved in the nerve growth factor-driven corneal wound healing process is clinically meaningful for the clinician. AS-OCT is an effective tool for systematic anterior segment imaging, allowing the detailed detection of the front-to-back layered corneal structure for quantitative analysis and monitoring of the healing process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bonzano, Olivari, Cutolo, Macrì, Sindaco, Borroni,.Bonzano and Traverso.)