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.

Accuracy of intraocular lens power calculation for cataract surgery after deep anterior lamellar keratoplasty.

BACKGROUND: The purpose of this study was to assess the accuracy of intraocular lens power (IOL) formulas for cataract surgery after deep anterior lamellar keratoplasty (DALK). METHODS: This retrospective study included eyes which had previously undergone DALK and underwent standard phacoemulsification with monofocal IOL implantation between January 2012 and January 2021 at Ospedali Privati Forlì "Villa Igea" (Forlì, Italy). The predicted spherical equivalent (SE) was calculated using the Barrett Universal II, Emmetropia Verifying Optical (EVO), Haigis, Hoffer Q, Hoffer QST, Holladay 1, Holladay II, Kane and SRK/T formulas. Prediction error (PE) was calculated as the actual postoperative SE refraction minus the SE predicted refraction. RESULTS: Eighty-two eyes of 82 patients were included. The mean PE was negative using all formulas. Friedman test revealed a statistically significant difference of the median absolute PE (MedAE) among the different IOL formulas (P = 0.005). On the basis of the MedAE, the formulas were ranked as follows: SRK/T (0.805 D), Kane (0.810 D), EVO (0.845 D), Hoffer QST (0.847 D), Barrett (0.895 D), Holladay 1 (0.915 D), Haigis (1.010 D) and Hoffer Q (1.070 D) formulas. CONCLUSIONS: All formulas had a tendency towards a myopic refractive shift in post-DALK eyes. Although the SRK/T, Kane, EVO and Hoffer QST formulas were more accurate, predictability of refractive outcomes was lower than in virgin eyes.

Retinal microcirculation abnormalities in patients with systemic sclerosis: an explorative optical coherence tomography angiography study.

OBJECTIVES: To investigate subclinical and clinical abnormalities in retinal and choroidal vascular plexuses in patients with SSc by means of optical coherence tomography angiography (OCT-A). METHODS: A total of 20 consecutive SSc patients were recruited and compared with 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CCP for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries. RESULTS: The DCP-VD in the whole scan and in the perifoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CCP-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers, significantly decreased SCP-VD was demonstrated in the whole, perifoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with and without interstitial lung disease. Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients. CONCLUSION: We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc.

Culture of corneal endothelial cells obtained by descemetorhexis of corneas with Fuchs endothelial corneal dystrophy.

Currently, endothelial keratoplasty is the gold standard for the surgical treatment of Fuchs endothelial corneal dystrophy (FECD). Despite the remarkable success in terms of surgical outcomes, a shortage of corneal donor tissue poses a limitation to performing endothelial keratoplasty in many parts of the world. Cell therapy is a potential alternative strategy to keratoplasty and is currently under investigation. Considering that corneas with FECD may contain relatively healthy endothelial cells, samples obtained by descemetorhexis of eyes undergoing EK for FECD can be used for ex vivo expansion of endothelial cells as an autologous cell culture. In this study, we established corneal endothelial cell cultures derived from 40 patients that underwent endothelial keratoplasty for advanced FECD. Several parameters were evaluated including patient characteristics such as age, gender, and endothelial cell density as well as various processing and cell culture protocols based on different combinations of shipping temperatures, stabilization periods and treatment methods for corneal endothelial cell dissociation. FECD cultures were classified into three groups as: (i) no cells, (ii) cell cultures with endothelial-like morphology or (iii) cell cultures with fibroblast-like features. Our data seem to suggest that some factors can influence FECD cell culture characteristics including young age, high paracentral endothelial cell density, low shipping temperature and short stabilization period prior to cell isolation. Treatment with type 1 collagenase for cell isolation can delay endothelial-to-mesenchymal transition, but does not increase proliferative capacity. Although heterologous corneal endothelial cultures from healthy donors have shown encouraging outcomes, the feasibility of autologous cell therapy as a potential treatment for FECD remains challenging. Low initial cell concentration as well as endothelial to mesenchymal transition are the main obstacles to the application of FECD cultures in the clinical setting.

Optimizing outcomes for keratoplasty in ectatic corneal disease.

PURPOSE OF REVIEW: Advanced keratectasia often requires corneal transplantation for restoration of vision. This review discusses the surgical approach suitable for these cases including significant updates in the current literature. RECENT FINDINGS: With greater understanding of ectatic corneal disease and its associated operative challenges, several modifications in the surgical approach have been developed. Identified predictive factors for successful pneumatic dissection and intraoperative complications have informed surgical planning and decision-making. In the setting of failed pneumatic dissection, sequential use of alternative lamellar dissection techniques is a reasonable surgical strategy. Surgical refinements to optimize visual outcomes and postoperative interventions to correct residual refractive errors have improved visual rehabilitation after keratoplasty. SUMMARY: With evidence of its undisputed advantages, DALK has been widely recognized as the primary surgical option for ectatic corneal disease.

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.

Outcomes of Corneal Transplantation for Herpetic Keratitis: A Narrative Review.

Herpes simplex virus (HSV) is one of the most common etiologic agents of corneal disease and a significant cause of corneal blindness worldwide. Although most cases can be successfully managed with medical therapy, HSV keratitis associated with visually significant stromal scarring often requires corneal transplantation for visual rehabilitation. While penetrating keratoplasty (PK) represented the traditional keratoplasty technique, the past few decades have seen a shift towards lamellar keratoplasty procedures, including deep anterior lamellar keratoplasty and mushroom keratoplasty. This paper describes the current surgical techniques and perioperative antiviral prophylaxis regimen for herpetic keratitis and reviews their postoperative clinical outcomes.

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.

Genetic Risk Factors and Clinical Outcomes in Childhood Eye Cancers: A Review.

Childhood eye cancers, although rare, present substantial health challenges, affecting the pediatric population with a remarkable impact on their lives and families. This comprehensive review provides insights into the various types of ocular tumors, primarily focusing on malignant eye tumors, their genetic predispositions, and advancements in managing these conditions. Understanding the genetic risk factors is crucial for early detection, risk assessment, and the development of targeted therapies. This review discusses genome-wide association (GWAS) and next-generation sequencing (NGS) studies to find common and rare genetic variants. Furthermore, it also explores the outcomes and implications of these genetic discoveries in treating pediatric ocular cancer. These findings underscore the significance of genetic research in guiding early interventions and improving outcomes in children with ocular cancers.

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 with Viscoat ophthalmic viscosurgical device (OVD) in patients undergoing routine cataract surgery. SETTING: 2 tertiary eyecare hospitals in Italy. DESIGN: Prospective randomized clinical trial. METHODS: This study compared the outcomes of Bio-Hyalur LVD vs Viscoat OVD 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-day, 7-day, 30-day, and 90-day mean intraocular pressure (IOP); 7-day, 30-day, and 90-day corrected distance visual acuity; endothelial cell density (ECD); change in central corneal thickness (CCT); and complications including intraocular inflammation. RESULTS: 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 = .034), 7 days ( P < .001), 30 days ( P < .001), and 90 days ( P = .003) postoperatively. Mean change in uncorrected distance visual acuity and corrected distance visual acuity was significantly higher in the Bio-Hyalur LVD group 30 and 90 days postoperatively. No significant differences in ECD, CCT, and complication rates were observed between groups at any timepoint. CONCLUSIONS: Bio-Hyalur LVD OVD was safe and effective in patients undergoing routine cataract surgery. Bio-Hyalur LVD OVD did not confer a higher risk of postoperative increase in IOP.

Longitudinal Changes of Cornea Volume Measured by Means of Anterior Segment-Optical Coherence Tomography in Patients with Stable and Progressive Keratoconus.

Keratoconus is a corneal disease which results in progressive thinning and protrusion of the cornea leading to irregular astigmatism. The purpose of this study was to evaluate longitudinal changes in corneal volume (CV) occurring over time in keratoconus eyes. Consecutive patients affected by keratoconus were evaluated by means of anterior segment-optical coherence tomography (AS-OCT) at two different time points: baseline (T0) and after 1 year (T1). Anterior and posterior refractive value; corneal thickness at the thinnest point (TP) and corneal volume (CV) calculated within discs of 3, 5 and 8 mm of diameter; anterior chamber depth (ACD); and anterior chamber volume (ACV) were obtained. Enrolled patients were divided into 3 groups (groups 1, 2, 3) according to the increasing disease severity and into 2 groups (groups A, B) according to the progression or stability of the disease. Overall, 116 eyes of 116 patients (76 males and 40 females, mean age 34.76 ± 13.99 years) were included. For the entire group of keratoconus patients, in comparison with T0, mean TP decreased at T1 from 458.7 ± 52.2 µm to 454.6 ± 51.6 µm (p = 0.0004); in parallel, mean value of CV calculated at 5 mm and 8 mm decreased significantly (from 10.78 ± 0.8 at T0 to 10.75 ± 0.79 at T1 (p = 0.02), and from 32.03 ± 2.01 mm3 at T0 to 31.95 ± 1.98 at T1 (p = 0.02), respectively). Conversely, there were no statistically significant differences in CV at 3 mm from T0 to T1 (p = 0.08), as well as for ACD and ACV. Regarding the course of the disease, patients belonging to group A showed statistically significant differences from T0 to T1 for TP, and for CV at 3 mm, 5 mm and 8 mm (p < 0.0001, p < 0.0001, p < 0.001 and p = 0.0058 respectively). There were no statistically significant differences for ACD (p = 0.6916) and ACV calculated at 3, 5 and 8 mm (p = 0.7709, p = 0.3765, p = 0.2475, respectively) in group A. At the same time, no statistically significant differences for ACD (p = 0.2897) and ACV calculated at 3, 5 and 8 mm (p = 0.9849, p = 0.6420, p = 0.8338, respectively) were found in group B. There were statistically significant positive correlations between changes of TP and CV at 3 mm (r = 0.6324, p < 0.0001), 5 mm (r = 0.7622, p < 0.0001) and 8 mm (r = 0.5987 p < 0.0001). In conclusion, given the strong correlation with TP, CV might be considered an additional AS-OCT parameter to be used in association with conventional parameters when detecting longitudinal changes in keratoconic eyes.

A Look into Ocular Diseases: The Pivotal Role of Omics Sciences in Ophthalmology Research.

Precision medicine is a new medical approach which considers both population characteristics and individual variability to provide customized healthcare. The transition from traditional reactive medicine to personalized medicine is based on a biomarker-driven process and a deep knowledge of biological mechanisms according to which the development of diseases occurs. In this context, the advancements in high-throughput omics technologies represent a unique opportunity to discover novel biomarkers and to provide an unbiased picture of the biological system. One of the medical fields in which omics science has started to be recently applied is that of ophthalmology. Ocular diseases are very common, and some of them could be highly disabling, thus leading to vision loss and blindness. The pathogenic mechanism of most ocular diseases may be dependent on various genetic and environmental factors, whose effect has not been yet completely understood. In this context, large-scale omics approaches are fundamental to have a comprehensive evaluation of the whole system and represent an essential tool for the development of novel therapies. This Review summarizes the recent advancements in omics science applied to ophthalmology in the last ten years, in particular by focusing on proteomics, metabolomics and lipidomics applications from an analytical perspective. The role of high-efficiency separation techniques coupled to (high-resolution) mass spectrometry ((HR)MS) is also discussed, as well as the impact of sampling, sample preparation and data analysis as integrating parts of the analytical workflow.

Surgical Strategies to Manage Stromal Interface Irregularity Following Deep Anterior Lamellar Keratoplasty.

PURPOSE: The purpose of this study was to describe the various surgical approaches to manage stromal interface irregularity following deep anterior lamellar keratoplasty (DALK). METHODS: This interventional case series included patients requiring repeat keratoplasty procedures for stromal interface opacity and/or irregularity following DALK. The following surgical techniques with the aim of restoring transparency and regularity of the central optical zone and improving visual acuity in eyes that underwent unsuccessful DALK were performed: 1) simple anterior lamellar graft exchange, 2) repeat DALK with pneumatic dissection, 3) repeat DALK with deepening of manual lamellar dissection, 4) small diameter stripping of the central stroma-endothelium-Descemet complex and its replacement with a new endothelial lamella, and 5) 2-piece microkeratome-assisted mushroom penetrating keratoplasty. Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), slit-lamp examination, tonometry, and anterior corneal tomography were evaluated preoperatively, as well as 3, 6, and 12 months after surgery. Intraoperative and postoperative complications were recorded. RESULTS: Preoperative BCVA was less than 20/200 and improved to 20/40 or better in all cases, reaching 20/20 in 1 patient. Corneal clarity was restored in all eyes, and no recurrence of underlying disease was observed. No intraoperative or postoperative complications were reported. CONCLUSIONS: This case series describes several successful surgical approaches to improve the transparency and regularity of stromal interface obtained after a DALK procedure; the choice of the technique should be customized for the single eyes to still maintain the advantages of lamellar or minimally invasive grafts.

Long-Term Evaluation of Patients with Neurotrophic Keratopathy Undergoing Staged Keratoplasty After Corneal Neurotization.

PURPOSE: Corneal neurotization (CN) is a novel, potentially curative surgical procedure for the treatment of neurothophic keratopathy (NK). Patients with severe NK can present with corneal opacification requiring optical keratoplasty, which would likely fail without a proper trophic support of corneal nerves in the recipient cornea. METHODS: This is a pilot study on 4 patients undergoing keratoplasty after CN. Pre- and postoperative data at 12, 24 months and at the last follow-up were collected for the examination of (i) best corrected visual acuity (BCVA), (ii) slit lamp examination and photograph acquisition with and without fluorescein staining, (iii) corneal aesthesiometry, (iv) in vivo confocal microscopy of the central cornea. Neurophysiological study of the corneal reflex before corneal graft and at last follow up was performed. RESULTS: Four female patients (47.25 ± 5.06 y.o.) underwent keratoplasty after CN (3 penetrating keratoplasty, 1 deep anterior lamellar keratoplasty). The mean interval between CN and keratoplasty was 22 (± 12) months. The mean graft survival time was 42 (± 25) months. Graft follow-up ranged from 72 to 132 months. At the final follow-up, BCVA was improved in 2 out of 4 patients. The mean corneal sensitivity was 11.9 ± 8.3 mm at last follow-up. In vivo confocal microscopy confirmed the presence of functioning nerves at the last follow-up in all patients. NK-related complications occurred in 3 eyes (2 persistent epithelial defect, 1 corneal melting). The former complication was successfully treated by autologous serum eye drops while the latter required repeated keratoplasty. CONCLUSIONS: Keratoplasty is a viable strategy to improve visual acuity in patients with corneal opacity who underwent CN for the treatment of NK. Even in the presence of functioning corneal nerves before keratoplasty, surgeons should be aware of the increased rate of NK-related complications that could require the need for repeated procedure.