Vascular Density and Retinal Function in Patients with Retinitis Pigmentosa Evaluated by Swept-Source OCT Angiography and Microperimetry.

PURPOSE: To determine the retinal and choroidal vessel density in the macular area with swept-source optical coherence tomography (OCT) angiography (SS-OCTA) in patients affected by retinitis pigmentosa (RP), to compare their data with those on healthy subjects, and to study a possible morphofunctional correlation by microperimetry (MP-1). METHODS: A total of 40 eyes of 40 patients affected by RP and 24 eyes of 24 healthy subjects were included in the study. Manually moving down the segmentation line of the SS-OCTA, we have evaluated the vessel density for the superficial retinal plexus, deep retinal plexus, choriocapillaris, and three levels of the choroid. RESULTS: Linear regression analyses were performed of the retinal structure and function. No significant correlation was detected in any case (R2 = 0, p > 0.05). A comparison between RP and healthy controls revealed a significant reduction in SS-OCTA mean capillary density in the RP group (p = 0.0011). This relationship was consistent across vascular layers (p = 0.2413). A significant association between the capillary density of the various vascular complexes was detected within individual eyes (p < 0.0001). CONCLUSIONS: This study represents the first comparing MP-1 and SS-OCTA data in the largest cohort of patients. RP patients showed a reduction in both the retinal and the choroidal vascular network in the macular area compared to healthy subjects.

Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty With Endothelium Inward: A 24-Month Comparative Analysis Between Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy.

PURPOSE: The aim of this study was to compare long-term clinical outcomes of preloaded Descemet membrane endothelial keratoplasty (DMEK) between Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK). METHODS: In this single-center retrospective clinical case series, 71 eyes of 64 patients indicated with FECD (62%) or BK (38%) (with or without cataract) were treated with preloaded DMEK grafts between March 2018 and February 2020. Standard DMEK peeling, followed by manual folding of the tissue with endothelium-inward orientation and storing in a preloaded fashion inside a 2.2-mm intraocular lens cartridge. All tissues were delivered using a bimanual pull-through technique, followed by air tamponade. Graft unfolding time, endothelial cell loss, corrected distance visual acuity, central corneal thickness, rebubbling rate, and intraoperative and postoperative complications at 1, 3, 6, 12, and 24 months were recorded. RESULTS: The mean intraoperative graft unfolding time in FECD did not differ from the BK group ( P = 0.6061). Cystoid macular edema did not differ in either group ( P = 0.6866). The rebubbling rate was found to be significantly higher in FECD compared with the BK group ( P = 0.0423). Corrected distance visual acuity significantly improved at the first month after surgery ( P = 0.0012), with no differences between FECD and BK at 24 months ( P = 0.2578). Central corneal thickness was stable postoperatively and showed no differences between the groups ( P = 0.3693). Significantly higher endothelial cell counts were observed in the FECD group at 24 months ( P = 0.0002). CONCLUSIONS: Preloaded DMEK with "endothelium-in" offers acceptable intraoperative time, rebubbling rate, and clinical outcomes in both FECD and BK groups. Patients with FECD show better postoperative clinical outcomes even if the rebubbling rate is relatively high.

Trabeculectomy versus Xen gel implant for the treatment of open-angle glaucoma: a 3-year retrospective analysis.

OBJECTIVE: To compare the two surgical techniques in terms of efficacy, safety, and postoperative management over 36 months of follow-up. METHODS: This retrospective clinical cohort study compared the outcome of trabeculectomy surgery and Xen gel implant in patients having uncontrolled glaucoma. Patients were recruited using the following inclusion criteria: uncontrolled intraocular pressure (IOP) on maximally tolerated medical therapy, healthy conjunctiva freely mobile in the superior sector, open-angle, glaucomatous visual field damage, full follow upfollow-up of at least 36 months. Thirty-four patients were submitted to trabeculectomy and 34 to Xen gel implant. We set the lower limit at 6mmHg mm Hg and the upper limit ≤12 mm Hg for criteria A, upper limit to ≤15 mm Hg for criteria B and upper limit ≤18 mm Hg for criteria C. Criteria for success have been characterizedcharacterised according to whether or not this has been achieved without (complete success) or with IOP -lowering medications (qualified success). RESULTS: For all survival curves, trabeculectomy was superior to Xen gel implant. When considering complete success, the log-rank test for criteria A was statistically significant (pp=0.006), marginally significant for criteria B (pp=0.065) and not significant for criteria C (pp=0.23). When qualified success was considered, trabeculectomy was superior to Xen gel for criteria A, B, and C (pp=0.012, pp=0.033 and pp=0.025, respectively). Higher number of post-operative flat chamber and bleb leakage was observed in the trabeculectomy group. CONCLUSION: Xen gel implant techniques offer a better safety profile but a lower IOP reduction compared to compared with the gold -standard technique.

Evaluation of macular vessel density changes after strabismus surgery using optical coherence tomography angiography.

PURPOSE: To compare retinal vessel density before and after strabismus surgery using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: In this longitudinal, single-arm pilot study, vascular density in the deep capillary plexus (DCP), superficial retinal capillary plexus (SCP) and choriocapillaris layer (CCL) in consecutive subjects undergoing strabismus surgery was assessed using SS-OCTA preoperatively (T0), on the first day postoperatively (POD1), and 30 days postoperatively (POD30). RESULTS: A total of 92 eyes of 56 patients (54% males) were included. Mean patient age was 41.1 ± 22.7. OCT vascular density of the DCP was 50.20 ± 5.57 at T0, 52.74 ± 4.77 at POD1, and 50.92 ± 4.58 at POD30. The differences were statistically significant for T0 versus POD1 (P < 0.05). Vascular density of the CCL was 50.72 ± 4.80 at T0, 53.59 ± 3.65 at POD1, and 51.39 ± 4.64 at POD30. The differences were statistically significant for T0 versus POD1 (P < 0.05). No significant differences were found in SCP (P > 0.05). CONCLUSIONS: Transitory hemodynamic changes can occur in the DCP and in the CCL following muscle recession procedures.

Delivering Endothelial Keratoplasty Grafts: Modern Day Transplant Devices.

PURPOSE: To summarize the graft loading, transporting and delivery devices used for endothelial keratoplasty (EK). METHODS: A literature search of electronic databases was performed. RESULTS: New techniques and devices have been introduced and implemented to prepare, load, transport and transplant the grafts for EK. The advantages are not only limited to the surgical theatre but also widely spread across the eye banking field. Investigation of advanced materials and designs have been rapidly growing with continuous evolution in the field of eye banking and corneal transplantation. Innovative techniques and modern devices have been evaluated to reduce the endothelial cell loss and increase the precision of the transplant in order to benefit both surgeons and the patients. CONCLUSIONS: It is extremely important to reduce any potential wastage and optimize the use of every available donor cornea due to the limited availability of healthy cadaveric donor corneas required for transplants. As a result, the use of pre-cut and pre-loaded grafts supplied by the eye banks in calibrated devices have been gaining momentum. Innovation in the field of bioengineering for the development of new devices that facilitate excellent clinical outcomes along with reduction in learning curve has shown promising results.

Biomaterials for corneal endothelial cell culture and tissue engineering.

The corneal endothelium is the posterior monolayer of cells that are responsible for maintaining overall transparency of the avascular corneal tissue via pump function. These cells are non-regenerative in vivo and therefore, approximately 40% of corneal transplants undertaken worldwide are a result of damage or dysfunction of endothelial cells. The number of available corneal donor tissues is limited worldwide, hence, cultivation of human corneal endothelial cells (hCECs) in vitro has been attempted in order to produce tissue engineered corneal endothelial grafts. Researchers have attempted to recreate the current gold standard treatment of replacing the endothelial layer with accompanying Descemet's membrane or a small portion of stroma as support with tissue engineering strategies using various substrates of both biologically derived and synthetic origin. Here we review the potential biomaterials that are currently in development to support the transplantation of a cultured monolayer of hCECs.

Evaluating the Correlation between Alzheimer's Amyloid-ß Peptides and Glaucoma in Human Aqueous Humor.

Purpose: Recent studies suggest that glaucoma may share common pathogenic mechanisms with Alzheimer's disease. To test this hypothesis, we investigated the correlation between glaucoma and amyloid-ß42 (Aß42) concentration in human samples of aqueous humor (AH). Methods: Eighty-one candidates for cataract or glaucoma surgery were consecutively enrolled, with a median age of 77 years; of these, 32 subjects were affected by glaucoma and 49 were controls. Before surgery, each patient received an ophthalmological examination including biometry, intraocular pressure (IOP) measurement, fundus photography, and determination of the mean thickness of the ganglion cell complex (GCC) and/or retinal nerve fiber layer. During the surgical procedure, an AH sample was collected and immediately processed for total protein (TP) and Aß42 evaluation. Results: Aß42 levels were not statistically different between the glaucomatous and control samples, but a significant increase in TP concentration was found in the AH of glaucoma patients compared with controls (P = 0.02). In addition, positive correlations were observed between TP and Aß42 (r = 0.51; P < 0.0001), between TP and IOP (r = 0.44; P < 0.0001), and between Aß42 and IOP (r = 0.22; P = 0.033). Conclusions: Our results indicate that an increased protein concentration in the AH could play a role in the pathogenesis of glaucomatous disease. Translational Relevance: This study strongly supports the hypothesis that increased TP in the AH may have a pathogenic role in glaucoma. Further investigations are needed to clarify whether the protein enhancement represents a causative factor and whether it can be used as a marker of disease or as a novel therapeutic target.

Neuroaxonal Degeneration in Patients With Multiple Sclerosis: An Optical Coherence Tomography and in Vivo Corneal Confocal Microscopy Study.

PURPOSE: To investigate the effect of multiple sclerosis (MS) on corneal and retinal nerve fiber by quantifying corneal subbasal nerve fibers and retinal ganglion cells. METHODS: A total of 46 eyes of 23 patients with MS and 42 eyes of 21 healthy subjects were included in the study. All patients and healthy subjects underwent a comprehensive ocular examination. In vivo confocal microscopy with Heidelberg Retina Tomograph in association with Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany) and a swept-source optical coherence tomography (Topcon Corporation) were performed in all patients and healthy subjects. The number of subbasal nerve fibers and the nerve fiber density were calculated. Student t test was used to compare eyes with MS with control eyes. The normal distribution was first confirmed with the Shapiro-Wilk test. RESULTS: A statistically significant (P < 0.05) decrease was found for nerve fiber number, ganglion cell-inner plexiform layer, and retinal nerve fiber layer in patients with MS compared with those of healthy subjects. Moreover, an inverse correlation was found between retinal nerve fiber layer (r = -0.32), nerve fiber number (r = -0.47), and ganglion cell-inner plexiform layer (r = -0.51) and Expanded Disability Status Scale. A direct correlation between Expanded Disability Status Scale and optic neuritis frequency was found (r = 0.322). CONCLUSIONS: In vivo confocal microscopy showed a difference in corneal morphological parameters and retinal damage; moreover, these changes seemed to be related to the degree of neurological disability. Both retinal ganglion and trigeminal cell atrophy measurements could become affordable and accessible biomarkers for clinical trials in progressive disease.

Corneal epithelial dendritic cells in patients with multiple sclerosis: An in vivo confocal microscopy study.

PURPOSE: To evaluate density and morphology of corneal epithelial dendritic cells (DCs) in patients with multiple sclerosis (MS) using in vivo confocal microscopy (IVCM). METHODS: This was a single-center cross-sectional comparative study. All MS patients were clinically scored using the Expanded Disability Status Scale (EDSS) score. Patients underwent ophthalmological examination and then cornea was analyzed by IVCM Heidelberg Retina Tomograph (HRT 3) in combination with Rostock Cornea Module and CCD camera. Five sectors (central, nasal, temporal, inferior, superior and central area) were analyzed in both patient eyes, then for each sector one image was selected and analyzed by using the manual cell counting system offered with the software and ImageJ program. DCs density (cell/mm2) and DCs size (µm2) were considered for the analyses. Difference between the two groups and correlation between DCs, MS type, EDSS score, optic neuritis and ongoing therapy were analyzed. RESULTS: We enrolled 46 consecutive patients: 23 with MS (age 47.87 ± 7.22 years (mean ± standard deviation) and 21 healthy subjects (age 46.0 ± 12.6 years) from July 2017 to July 2018. MS patients showed a lower DCs density when compared with healthy subjects (p < 0.05). Moreover, we found a direct correlation (r:0.48, p < 0.05) between DCs density and ongoing disease-modifying therapy. CONCLUSION: IVCM was able to show a difference in corneal DCs density between MS patients and healthy subjects, providing an insight to the underlying changes of the clinical manifestations of MS. Further studies are needed to provide evidence of possible clinical implications.

Early Postoperative Intraocular Pressure is Associated With Better Pressure Control After XEN Implantation.

PRéCIS:: Gel stent implantation is a bleb-forming surgery designed to achieve predictable pressure drop. An early low intraocular pressure (IOP) is associated with the long-term success of the procedure. PURPOSE: To identify the variables associated with the success of the XEN procedure. PATIENTS AND METHODS: This was part of a prospective, uncontrolled, consecutive case series study. Patients with primary open-angle glaucoma or pseudo-exfoliative glaucoma were included. All the patients underwent surgical XEN implant procedure with mitomycin-C subconjunctival injection 20 minutes before surgery. Success criteria were an off-medication IOP of 6 to 16 mm Hg 12 months after surgery; no additional glaucoma surgery; no visual threatening complications, no visual acuity loss >1 Snellen line. One eye per patient was considered for statistical analysis. A univariate Cox proportional hazard regression analysis was performed to identify potential risk factors for surgical failure. Then, a multivariate Cox model was built. RESULTS: One hundred twenty-three patients were recruited in this study: 93 patients underwent XEN implantation alone whereas 30 the combined procedure with phacoemulsification and intraocular lens implantation. Univariate Cox regression showed that the day after surgery intraocular lens>9 mm Hg was associated with surgical failure (P=0.02) and a postoperative number of needlings ≥2 in the follow-up was also predictive of surgical failure (P<0.01). These data were confirmed by a multivariate model too. At 1 year the surgical success criteria were 76% in the group with 24-hour IOP≤9 mm Hg, whereas it was 43% when above 9 mm Hg (P=0.026). CONCLUSIONS: Our study shows that an early IOP≤9 mm Hg is predictive of the efficacy of the procedure during 1-year follow-up, whereas more than 2 needlings are predictive of failure.

XEN Implant Fracture During Needling Procedure.

PURPOSE: The XEN implant is a small hydrophilic stent designed to be implanted permanently for the treatment of glaucoma. As with other bleb-forming surgical procedures, needling is part of postoperative care. We describe 3 cases of XEN fracture of the subconjunctival portion that occurred during the needling procedure. METHODS: The purpose of this study was to describe the clinical and anatomic outcomes in 3 cases of XEN fracture caused by the needling procedure. RESULTS: In our case series of XEN procedures (n=170), bleb needling has been performed in 98 cases (57.6%). In 3 cases (3.1%), we observed unintentional damage to the implant after the procedure.The mean distal segment length of the fractured XEN measured 0.83 (range: 0.7 to 1) mm. Despite the adverse event, the mean IOP changed from 25.0 (range: 21 to 30) mm Hg before needling to 12.0 (range: 10 to 14) after needling, with a mean follow-up of 15.3 (range: 11 to 18) months. No vision-threatening complications were recorded during the entire follow-up. CONCLUSIONS: XEN fracture related to the needling procedure should be considered as a possible adverse event of bleb management. Because XEN is composed of a soft and flexible gelatin material, it could be easily damaged by the needle. The fracture does not seem to impair the efficacy of the draining device. As a matter of fact, according to Poiseuille's laws, shortening of the implant's length decreases the resistance while increasing the flow rate. Despite our positive results, it is recommended to preserve the integrity of the implant.

The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study.

Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n = 20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n = 10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p < 0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications.