Prospective Randomized Clinical Trial Evaluating Efficacy and Safety of A New Ophthalmic Viscosurgical Device In Patients Undergoing Cataract Surgery.

PURPOSE: To evaluate the efficacy and safety of Bio-Hyalur LVD compared to Viscoat® ophthalmic viscosurgical device (OVD) in patients undergoing routine cataract surgery. SETTING: Two tertiary eye care hospitals in Italy. DESIGN: Prospective randomized clinical trial. METHODS: This study compared the outcomes of Bio-Hyalur LVD versus Viscoat® ophthalmic viscosurgical device in patients undergoing standard cataract surgery with phacoemulsification and intraocular lens implantation from January 2021 to April 2022. The primary outcome was mean change in IOP at 6 hours. Secondary outcomes included 1-, 7-, 30- and 90-day mean intraocular pressure (IOP), 7-, 30- and 90-day best corrected visual acuity, endothelial cell density (ECD), change in central corneal thickness (CCT) and complications including intraocular inflammation. RESULTS: A total of 84 eyes of 84 patients (n = 41 in the Bio-Hyalur LVD group and n = 43 in the Viscoat group) were screened, enrolled, randomized, and included in the analysis. Mean change in IOP was significantly higher in the Viscoat group than in the Bio-Hyalur LVD group 6 hours (p = 0.034), 7 days (p < 0.001), 30 days (p < 0.001) and 90 days (p = 0.003) postoperatively. Mean change in UDVA and CDVA was significantly higher in the Bio-Hyalur LVD group 30 and 90 after surgery. No significant differences in ECD, CCT and complication rates were observed between groups at any time point. CONCLUSION: Bio-Hyalur LVD OVD is safe and effective for use in patients undergoing routine cataract surgery. Bio-Hyalur LVD OVD did not confer a higher risk of postoperative increase in IOP.

Large-diameter deep anterior lamellar keratoplasty: A narrative review.

Deep anterior lamellar keratoplasty (DALK) involves the selective replacement of diseased corneal stroma while preserving healthy unaffected endothelium. While DALK has failed to gain widespread popularity, improved visual and refractive outcomes of large-diameter grafts, which patients directly perceive following suture removal, may represent a compelling reason to shift toward DALK. Since the unaffected host endothelium is retained, DALK offers the opportunity to use large-diameter grafts, which reliably achieves maximum visual potential without an increased risk of immune-mediated stromal rejection. In this narrative review, we evaluate the current evidence on large-diameter DALK including surgical technique and clinical outcomes.

IC3D Classification of Corneal Dystrophies-Edition 3.

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature. METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)]. RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4. Lisch epithelial corneal dystrophy, previously reported as X-linked, has been discovered to be autosomal dominant ( MCOLN1 mutations, chromosome 19). Classic lattice corneal dystrophy (LCD) results from TGFBI R124C mutation. The LCD variant group has over 80 dystrophies with non-R124C TGFBI mutations, amyloid deposition, and often similar phenotypes to classic LCD. We propose a new nomenclature for specific LCD pathogenic variants by appending the mutation using 1-letter amino acid abbreviations to LCD. Pre-Descemet corneal dystrophies include category 1, autosomal dominant, punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) ( PRDX3 mutations, chromosome 10). Typically asymptomatic, it can be distinguished phenotypically from pre-Descemet corneal dystrophy, category 4. We include a corneal dystrophy management table. CONCLUSIONS: The IC3D third edition provides a current summary of corneal dystrophy information. The article is available online at https://corneasociety.org/publications/ic3d .

Outcomes of large-diameter deep anterior lamellar keratoplasty and converted two-piece mushroom penetrating keratoplasty for herpetic corneal scars.

PURPOSE: To report the clinical outcomes of large diameter deep anterior lamellar keratoplasty (DALK) and converted two-piece microkeratome-assisted mushroom keratoplasty (MK) for herpetic corneal scars. METHODS: In this single-centre study, large diameter (9 mm) DALK was attempted in consecutive patients with herpetic corneal scars. In case of macroperforation or unsatisfactory clearance of the optical zone, the procedure was intraoperatively converted to two-piece microkeratome-assisted MK. Outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism, endothelial cell density (ECD), immunologic rejection, herpetic recurrence and graft failure rates in the two groups. RESULTS: DALK was successfully performed in 98 of 120 eyes, while the remaining 22 eyes required intraoperative conversion to MK. At 5 years, mean logMAR BSCVA was 0.10 ± 0.12 in the DALK group and 0.09 ± 0.15 in the MK group (P = 0.75). Refractive astigmatism at 5 years was 2.8 ± 1.4 D in the DALK group and 3.0 ± 1.7 D in the MK group (P = 0.67). ECD was higher in the DALK group than in the MK group at all time points (P < 0.001), with a mean annual cell loss of 10.9% after MK and 4.2% after DALK. The 5-year risk for immunologic rejection (DALK: 3%, MK: 5%, P = 0.38), herpetic recurrence (DALK: 6%, MK: 9%, P = 0.38), and graft failure (DALK: 4%, MK: 5%, P = 0.75) were comparable in both groups. CONCLUSION: Large diameter (9 mm) DALK yields excellent visual and clinical outcomes in eyes with herpetic corneal scars. In case of intraoperative complications, DALK can be converted to two-piece microkeratome-assisted MK to maximize the refractive benefit of a large diameter graft while minimizing the risk of endothelial failure.

Deep Anterior Lamellar Keratoplasty Using Dehydrated versus Standard Organ Culture-Stored Donor Corneas: Prospective Randomized Trial.

PURPOSE: To compare the outcomes of deep anterior lamellar keratoplasty (DALK) using dehydrated versus standard organ culture-stored donor corneas for eyes with keratoconus. DESIGN: Prospective, randomized, single-center trial conducted in Italy. PARTICIPANTS: Adult patients (age ≥ 18 years) with keratoconus scheduled for elective DALK. METHODS: Patients undergoing successful type 1 bubble pneumatic dissection using a standard DALK technique were randomized during surgery to receive either dehydrated (n = 30) or standard organ culture-stored (n = 30) donor corneas. MAIN OUTCOME MEASURES: The primary study outcome was best spectacle-corrected visual acuity (BSCVA) 12 months after surgery. Secondary outcomes were refractive astigmatism (RA), endothelial cell density (ECD), and complication rates. RESULTS: Postoperative BSCVA did not significantly differ between groups at both time points: mean difference at 6 months was 0.030 logarithm of the minimum angle of resolution (logMAR; 95% confidence interval [CI], -0.53 to 0.10 logMAR; P = 0.471) and at 12 months was -0.013 logMAR (95% CI, -0.10 to 0.08 logMAR; P = 0.764). No significant differences between groups were observed in terms of postoperative RA and ECD at all time points. In the first 3 days after DALK, an epithelial defect was present in 10 patients (33%) in the organ culture cornea group and in 29 patients (97%) in the dehydrated cornea group. Complete re-epithelialization was achieved by day 7 in all patients (100%) in both groups. CONCLUSIONS: The study provides evidence that the use of dehydrated corneas is noninferior to the use of standard organ culture donor corneas for DALK. Corneal tissue dehydration represents a viable solution that can allow long-term cornea preservation and avoid wastage of unused corneas. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies.

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival and corneal tumors, retinoblastoma, uveal melanoma, and intraocular melanoma. As non-selective cancer chemotherapies as well as ionizing radiation can be associated with either poor efficacy or dose-limiting toxicities in the eye, reconstitution of the p53 signaling pathway currently represents an attractive target for cancer therapy. The present review discusses the role of p53 in the pathogenesis of these ocular tumors and outlines the various pharmacological activators of p53 that are currently under investigation for the treatment of ocular malignancies.

Microsporidial Stromal Keratitis in Post-Keratoplasty Eyes.

PURPOSE: The purpose of this paper is to report the clinical manifestations, diagnostic evaluation, management and outcomes of microsporidial keratitis in post-keratoplasty eyes. METHODS: This is a retrospective review of three patients diagnosed with microsporidial stromal keratitis in post-keratoplasty eyes between January 2012 and December 2021 at a tertiary referral center (Ospedali Privati Forlì "Villa Igea", Forlì, Italy). RESULTS: All patients presented with fine multifocal granular infiltrates following keratoplasty for a presumed herpetic keratitis. No microorganisms were isolated from the corneal scrapings and no clinical response was observed with broad-spectrum antimicrobial therapy. In all cases, confocal microscopy demonstrated spore-like structures. The histopathologic examination of the excised corneal buttons confirmed the diagnosis of microsporidial stromal keratitis. Following therapeutic keratoplasty and treatment with an initial high dose and extended taper of topical fumagillin, clinical resolution was achieved in all eyes. The Snellen visual acuities at the final follow-up were 20/50, 20/63 and 20/32. CONCLUSIONS: Prior to definitive surgery, confocal microscopy can be employed for the in vivo detection of pathogenic microorganisms such as Microsporidium. In post-keratoplasty eyes, therapeutic keratoplasty and an initial high dose of topical fumagillin with extended taper can allow the resolution of microsporidial stromal keratitis with a satisfactory visual prognosis.

Impact of topographic hot spots on the refractive outcomes of combined DMEK and cataract surgery.

PURPOSE: To compare the refractive results of combined Descemet membrane endothelial keratoplasty (DMEK) and cataract surgery in eyes with Fuchs endothelial corneal dystrophy (FECD) with and without topographic hot spots. SETTING: "Villa Igea" Hospital, Forlì, Italy. DESIGN: Interventional case series. METHODS: 57 eyes of 52 patients with FECD undergoing combined DMEK, cataract surgery, and monofocal intraocular lens (IOL) implantation were included in this single-center study. Patients were classified based on the presence or absence of topographic hot spots on the preoperative axial power map. Prediction error (PE) was calculated as the postoperative manifest spherical equivalent (SE) refraction minus the SE predicted refraction. RESULTS: 6 months postoperatively, mean PE was +0.79 ± 1.12 diopters (D). In eyes with hot spots, mean keratometry (K), K flat, and K steep significantly decreased after surgery (all P < .05), whereas no significant changes were observed in eyes without hot spots (all P > .05). Eyes with hot spots showed a significantly more hyperopic PE than eyes without hot spots (+1.13 ± 1.23 vs +0.40 ± 0.86 D; P = .013). CONCLUSIONS: Combined DMEK and cataract surgery can result in a hyperopic refractive surprise. The presence of topographic hot spots before surgery is associated with a higher hyperopic shift.

Outcomes of Conventional 8.0-mm Versus Large 9.0-mm Diameter Deep Anterior Lamellar Keratoplasty for Keratoconus.

PURPOSE: The purpose of the study was to compare the clinical outcomes of large 9.0-mm diameter and conventional 8.0-mm big-bubble deep anterior lamellar keratoplasty (DALK). METHODS: In this comparative, retrospective interventional case series, medical records of 124 cases of large 9.0-mm diameter DALK from January 2017 to December 2019 and 133 conventional 8.0-mm DALK from January 2014 to December 2016 performed by a single surgeon for the indication of keratoconus were reviewed. Main outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), and postoperative complication rates. RESULTS: Postoperative logarithm of the minimum angle of resolution BSCVA did not significantly differ between 9.0-mm and 8.0-mm DALK at any time points. Although the cumulative percentage of eyes achieving Snellen BSCVA of 20/40 or better was comparable between groups (9.0-mm DALK: 93%, 8.0-mm DALK: 90%, P = 0.571), the cumulative percentage of eyes achieving 20/20 or better (9.0-mm DALK: 44%, 8.0-mm DALK: 26%, P = 0.01) and 20/25 or better (9.0-mm DALK: 74%, 8.0-mm DALK: 59%, P = 0.03) was significantly higher in the 9.0-mm DALK group. RA was significantly lower in the 9.0-mm DALK group compared with the 8.0-mm DALK group during all time points ( P < 0.001). The percentage of eyes with RA less than or equal to 4.0 D was significantly lower in the 9.0-mm DALK patients (90%) compared with in 8.0-mm DALK group (72%) ( P = 0.002). Postoperative complication rates were similar between groups. CONCLUSIONS: Compared with conventional 8.0-mm DALK, large 9.0-mm DALK can provide superior visual outcomes at higher levels of Snellen BSCVA and significantly lower degrees of astigmatism without an increased risk of immune rejection and graft failure.

Stromal peeling for deep anterior lamellar keratoplasty in a post-penetrating keratoplasty eye with hematocornea.

Purpose: To present a case of hematocornea occurring in a post-penetrating keratoplasty (PK) eye and to report the outcomes of deep anterior lamellar keratoplasty (DALK) performed by simple stromal peeling. Observations: A 45-year-old female presented with hematocornea in the left eye that previously underwent PK 26 months prior for keratoconus. Clinical examination revealed a dense reddish-brown opacity within the PK graft which was associated with deep corneal neovascularization. Over 6 months, intracorneal hemorrhage developed a rust-colored appearance with minimal clearing. DALK was performed using the stromal peeling technique for post-PK eyes. Briefly, a dense partially organized hemorrhage was identified at the natural plane of separation, as confirmed by ex vivo histologic examination; after peeling of the deep corneal stroma and evacuation of the intracorneal hemorrhage, the residual bed appeared akin to pre-Descemet's layer-Descemet membrane-endothelium complex. One year after DALK, the graft remained clear with ECD of 1034 cells/mm2. Conclusions and Importance: Intracorneal hemorrhage is a rare but potentially sight-threatening complication following PK. Using the stromal peeling technique, DALK can be attempted to preserve functional endothelium in post-PK eyes. In the presence of a dense intracorneal hemorrhage, the spread of erythrocytic debris within the stroma can guide deep lamellar cleavage.

Large-Diameter Modified Big-Bubble Deep Anterior Lamellar Keratoplasty in Post-Radial Keratotomy Eyes.

PURPOSE: To report the outcomes of our modified large-diameter (9-mm) big-bubble deep anterior lamellar keratoplasty (DALK) technique with improved success rates of pneumatic dissection in post-radial keratotomy (RK) eyes. DESIGN: Retrospective case series. METHODS: At Ospedali Privati Forlì, "Villa Igea," Forlì, Italy., modified big-bubble DALK was performed in consecutive post-RK eyes. The technique included large-diameter (9-mm) deep partial-thickness trephination based on the thinnest anterior segment optical coherence tomography pachymetry value at 9 mm, air injection through a cannula advanced 2 mm centripetally from the base of the trephination, limited stromal clearance of the central 6-mm optical zone, and suturing of a 9-mm anterior lamellar graft prepared by microkeratome dissection. Success rate of pneumatic dissection, corrected distance visual acuity (CDVA), keratometric astigmatism, and complications were recorded. RESULTS: Eight eyes of 7 patients were included. Pneumatic dissection succeeded in 7 cases (87.5%). CDVA significantly improved from 0.94 ± 0.43 to 0.14 ± 0.06 logMAR (P < .001). All eyes reached Snellen CDVA ≥20/40, whereas 3 eyes (37.5%) reached ≥20/25. At the last follow-up, 5 eyes (62.5%) had a final keratometric astigmatism ≤4 diopters, whereas 2 eyes (25.0%) had ≤2 diopters. CONCLUSION: Big-bubble DALK can be successfully performed in post-RK eyes with our standardized technique.

A lack of an association between COVID-19 vaccination and corneal graft rejection: results of a large multi-country population based study.

PURPOSE: The aim of the study was to present the rates of corneal transplant rejection from 2018 to 2022 at both Moorfields Eye Hospital UK, and Ospedali Privati Forli (OPF) "Villa Igea", Italy and evaluate the purported association between COVID-19 vaccination and rejection. METHODS: We performed a retrospective review of rejection cases presenting to the two units. Monthly rates were correlated against regional vaccination programme rates. At OPF, conditional Poisson regression model was employed to estimate the incidence risk ratio (IRR) of graft rejection following COVID-19 vaccination risk period compared with the control period. RESULTS: Between January 2018 and March 2022, there were 471 (Moorfields), 95 (OPF) episodes of rejection. From the start of vaccination programme in the UK in late January 2021, the median number of graft rejections per month at Moorfields was 6 (range: 5-9), which was not significantly different to post-lockdown, pre-vaccination programme (March 2020-January 2021), p = 0.367. At OPF, the median rates of rejection before and after initiation of the vaccination programme were not significantly different (p = 0.124). No significant increase in incidence rate of rejection in the risk period following COVID-19 vaccination was found (IRR = 0.53, p = 0.71). CONCLUSION: No notable increase in rates of transplant rejection was noted in year 2021 when COVID-19 vaccination was broadly implemented. The apparent temporal relationship between COVID-19 vaccination and corneal graft rejection highlighted in several case reports may not represent a causative association.

Factors predictive of cystoid macular oedema following endothelial keratoplasty: a single-centre review of 2233 cases.

AIMS: To describe the incidence of postoperative cystoid macular oedema (CMO) after endothelial keratoplasty (EK) and to identify its contributory risk factors. METHODS: 2233 patients undergoing EK at Ospedali Privati Forlì 'Villa Igea', between January 2005 to October 2018 for Descemet stripping automated endothelial keratoplasty (DSAEK) and June 2014 to August 2018 for Descemet membrane endothelial keratoplasty (DMEK) with a minimum follow-up of 18 months were evaluated. Univariate and multivariate analyses were conducted to identify and quantify contributory risk factors. Receiver operating characteristic (ROC) curve analysis were performed to determine ideal cut-off points of continuous variables. RESULTS: CMO was identified in 2.82% (n=63) of the cases. CMO occurred in 2.36% of DSAEK eyes and in 5.56% of DMEK eyes (p=0.001). Average onset of CMO was 4.27±6.63 months (range: 1-34 months) postoperatively. Compared with those who did not develop CMO, a higher proportion of patients in the CMO group had diabetes (24.2% vs 9.8%, p<0.001) (OR=3.16, 95% CI: 1.72 to 5.81, p<0.001), a higher proportion of patients who underwent DMEK rather than DSAEK (28.6% vs 14.1%, p=0.001) (OR=2.42, 95% CI: 1.35 to 4.33, p=0.003) and were older (70.5±10.0 vs 67.1±14.3 years, p=0.01). Using the cut-off of 67 years as identified by ROC curve analysis, subjects aged >67 years (OR=2.35, 95% CI: 1.30 to 4.26, p=0.005) were more likely to develop CMO. There were no other significant differences between the groups. CONCLUSIONS: Older age (>67 years), diabetes mellitus and DMEK have been identified as independent risk factors for postoperative CMO following EK. Close observation is necessary during the first postoperative year after EK, particularly in patients with risk factors.

Bibliometric Analysis of Ophthalmology Publications from Arab Countries between 2012 and 2022.

PURPOSE: The purpose of this study was to conduct a bibliometric analysis of articles published in Ophthalmology Journals from Arab countries from 2012 to 2022. METHODS: This cross-sectional analysis of all original ophthalmology research and review articles published by authors with an affiliation with an institution from Arab countries and indexed in the ISI Web of Science between January 2012 and December 2022. RESULTS: For the years 2012-2022, 4292 articles published in Ophthalmology Journals by authors from Arab-based institutions were identified. A 2.11-fold progressive increase in the number of publications was observed over the last decade with a substantial increase in publication volume during the first 2 years of the COVID-19 pandemic. The countries with the highest number of publications were Egypt (38.51%), Saudi Arabia (35.56%), and the United Arab Emirates (7.88%). According to affiliation, authors from King Khaled Eye Specialist Hospital (KKESH) (n = 644) published the highest number of ophthalmology articles, followed by King Saud University (n = 585) and Cairo University (n = 393). CONCLUSION: Over the last decade, the overall productivity of research in the field of ophthalmology has significantly increased. Majority of the articles in ophthalmology were published by authors from Egypt and Saudi Arabia with KKESH as the most productive institution among Arab nations.

The role of the mTOR pathway in diabetic retinopathy.

The retina, the part of the eye, translates the light signal into an electric current that can be sent to the brain as visual information. To achieve this, the retina requires fine-tuned vascularization for its energy supply. Diabetic retinopathy (DR) causes alterations in the eye vascularization that reduce the oxygen supply with consequent retinal neurodegeneration. During DR, the mammalian target of rapamycin (mTOR) pathway seems to coordinate retinal neurodegeneration with multiple anabolic and catabolic processes, such as autophagy, oxidative stress, cell death, and the release of pro-inflammatory cytokines, which are closely related to chronic hyperglycemia. This review outlines the normal anatomy of the retina and how hyperglycemia can be involved in the neurodegeneration underlying this disease through over activation or inhibition of the mTOR pathway.

Deep anterior lamellar keratoplasty for keratoconus: Elements for success.

Advanced keratoconus may require keratoplasty when the patient can no longer achieve functional vision with glasses and contact lenses. Deep anterior lamellar keratoplasty (DALK) has become the surgical treatment of choice due to its undisputed advantages over penetrating keratoplasty including the reduced risk of intraoperative complications, the absence of endothelial immune rejection, and the longer graft survival. Albeit "big-bubble" DALK still represents the most popular surgical method, several modifications have been developed over the years. This allowed standardization of the technique, with improved success rates and clinical outcomes. This review presents an overview on the literature on DALK surgery for keratoconus. We discuss state-of-the art surgical techniques, current evidence on the clinical outcomes and complications as well as possible future directions.