Corneal Endothelial Cell Loss Research Articles

Improved Femtosecond Laser-Assisted Phacoemulsification of Hard Nucleus Cataract

Purpose: The development and clinical study of improved femtosecond laser-assisted phacoemulsification (PE) technology of hard nucleus cataract.Patients and methods. Improved femtosecond laser-assisted PE of hard nucleus cataract performed in 83 patients (93 eyes) (1st group), known femtosecond laser-assisted PE technique performed in 72 patients (78 eyes) (2nd group), torsional PE performed in 81 patients (89 eyes) (3rd group). The degree of intraoperative myosis, effective ultrasound time, corneal endothelial cell loss were evaluated in all groups.Results. Femtosecond laser-assisted PE is an effective technique for hard nucleus cataract removal, which can significantly reduce the energy ultrasonic load on the eye tissue. The proposed method for the instillation of prostaglandin synthesis inhibitors and the observance of the minimum possible interval between the first and second stages of the operation can prevent significant intraoperative narrowing of the pupil. A significant narrowing of the pupil by more than 2 mm after the femtolaser stage was noted in 7 (7.5 %) cases in the 1st group of patients, in 15 (16.9 %) cases in the 2nd group, in 5 (6.4 %) cases in the 3rd group. The results of the study has shown a significant decrease in the effective ultrasound time for a femtosecond laser-assisted PE compared with a torsional PE. The effective ultrasound time was in the 1st group (improved technology of femtosecond laser-assisted PE) — 3.81 ± 0.75, in the 2nd group (known technology of the femtosecond laser-assisted PE) — 5.23 ± 1.07 s (p < 0.05), in the 3rd group (OZil technology) — 8.67 ± 1.83 s (p < 0.05). The decrease in the effective ultrasound time has become a determining factor in reducing the loss of corneal endothelial cells in both femtosecond laser-assisted PE technologies compared to torsional PE. The average loss of corneal endothelial cells 3 months after surgery was 8.7 ± 1.8 % in the 1st group, 10.3 ± 2.1% in the 2nd group, 13.5 ± 2.7 % (p < 0.05) in the 3rd group of patients.Conclusion. The proposed improved technology contributes to the solution of some problems that characterize femtosecond laser-assisted PE, and also helps to reduce the effective ultrasound time and the loss of corneal endothelial cells.

Long-Term Destiny of Corneal Endothelial Cells in Anterior Chamber Intraocular Lens-Implanted Eyes.

Purpose To investigate the long-term changes of corneal endothelial cells (EC) in anterior chamber intraocular lens- (AC-IOL-) implanted eyes. Methods Retrospective study. We included 37 eyes (25 patients) that received AC-IOL implantation previously in the Eye and ENT Hospital of Fudan University between 1995 and 2016. Follow-up outcomes included the best-corrected visual acuity (BCVA), endothelial cell density, hexagonality, coefficient of variance, and central corneal thickness. Results In total, 23 eyes (62.16%) with phakic and 14 eyes (37.84%) with aphakic AC-IOLs were included. Among these, 3 eyes (8.11%) were angle-supported AC-IOLs and 34 eyes (91.89%) were Artisan iris-fixated AC-IOLs. The mean age of patients was 41.40 ± 17.17 years, and the mean follow-up time was 12.12 ± 4.71 years in our study. At the follow-up time, corneal decompensation existed in 3 angle-supported AC-IOL eyes with a rate of 100% and 15 iris-fixated AC-IOL eyes with a rate of 44.12%. AC-IOL displacement occurred in 14 (41.18%) iris-fixated AC-IOL eyes. In the 19 iris-fixated AC-IOL eyes without corneal decompensation, significant changes also took place in corneal endothelial cells. The endothelial cell density decreased from 2843.26 ± 300.76 to 2015.58 ± 567.99 cells/mm2 (29.1% loss, P < 0.001) and hexagonality decreased from 51.21 ± 7.83 to 42.53 ± 9.17 (%) (16.9% loss, P < 0.001). The Kaplan–Meier survival curve also demonstrated the accumulated expectation rates of corneal endothelial cell decomposition for AC-IOLs with a median survival time of 12 years. Conclusion We reported a significant chronic loss and long-term decompensation destiny of corneal endothelial cells in AC-IOL eyes. Semiannual or annual follow-up and evaluation of endothelial cells should be conducted in AC-IOL-implanted patients.

Comparative study of endothelial cell loss in trabeculectomy with combined small incision cataract surgery (SICS), trabeculectomy procedure and temporal small incision cataract surgery (SICS) alone

When a patient suffers from co-existing cataract and glaucoma, the choice of surgery may be a combined procedure of cataract extraction and trabeculectomy as a one-stage procedure, or trabeculectomy first to restore visual rehabilitation and to prevent progressive optic nerve damage. The main purpose of this study was to evaluate the endothelial cell loss in trabeculectomy with small incision cataract surgery (SICS) against trabeculectomy and SICS alone. Materials and Methods: This study was conducted on 90 eyes divided into 3 groups among whom 30 cases underwent trabeculectomy through a superior incision, 30 cases underwent SICS with PC-IOL implantation with trabeculectomy through a common superior incision and 30 patients underwent manual SICS with PCIOL. The corneal endothelial cell count and loss was assessed on first postoperative day, 1st week, 1st month and at 3 months. IOP was assessed on postoperative 1st week, 1st month and at 3 months. Results: The endothelial cell loss was more in combined SICS with trabeculectomy group than trabeculectomy group alone. Conclusion: Preoperative evaluation of endothelial cell count must be considered and adequate intra-operative and postoperative measures should be taken to avoid cell loss. However, to avoid further endothelial cell loss due to a two staged surgery, a combined procedure would be a better choice. Combined SICS with trabeculectomy would also reduce the economical burden, postoperative morbidity and the visits of patient to operation theatre. Keywords: Cataract, Endothelial cell loss, Glaucoma, SICS, Trabeculectomy.

Analysis of aqueous humor total antioxidant capacity and its correlation with corneal endothelial health.

Corneal endothelial decompensation is a serious condition that frequently requires treatment via corneal transplantation which contributes to a global shortage in donor corneas. Therefore, the purpose of this study was to analyze the influence of aqueous humor total antioxidant capacity (TAC) on corneal endothelial health. There is an urgent need for discovering protective factors to combat corneal endothelial cell (CEC) loss. For methods, we developed a cupric ion‐based TAC (CuTAC) assay to analyze TAC level in a small volume of aqueous humor, that is, 10 μL per test, and examined the influences of ascorbic acid (AA) and antioxidant proteins on aqueous humor TAC. To broaden the investigation, we conducted a case–control study with patients classified into two groups, an insufficient endothelial cell density (ECD < 2100 cells/mm2) group, and a control group. These groups were formed based on baseline ECD values and were used to evaluate the influence of aqueous humor TAC and AA on overall corneal endothelial health. A CuTAC assay was used to accurately measure aqueous humor TAC without the need for sample dilution. After analyzing a total of 164 human aqueous humor samples, we found that AA was the major contributor to aqueous humor TAC (73.2%). In addition, TAC and AA levels in the IECD and control groups were both found to be significantly different (1.168 vs. 1.592 mM, p = 0.009 and 0.856 vs. 1.178 mM, p = 0.016). TAC and AA were considered independent protective factors against IECD with adjusted odds ratios of 0.02 (p = 0.017) and 0.023 (p = 0.033), respectively. In conclusion, aqueous humor TAC and AA contribute to the maintenance of sufficient corneal ECD, and our CuTAC assay can be a useful tool for analyzing TAC using only a small aqueous humor sample volume.

Corneal Endothelial Cell Loss after Phacoemulsification in Eyes with a Prior Acute Angle-closure Attack.

PurposeTo evaluate endothelial damage after cataract surgery in eyes affected by an angle-closure attack (ACA) and compare it to that in the unaffected fellow eyes (FEs) of patients with ACA and normal eyes (NEs).MethodsThe medical data of eyes affected by ACA, FEs (with no history of acute glaucoma attack), and NEs of patients who underwent cataract surgery with simultaneous intraocular lens implantation were retrospectively reviewed. Endothelial cell density (ECD) and central corneal thickness (CCT) measured before surgery and at 1 week, 1 month, and 3 months after surgery were analyzed, and the percentages of loss in ECD and increase in CCT of the three groups were compared.ResultsThe study enrolled 140 eyes from 100 patients (50 eyes in the ACA group, 40 eyes in the FE group, and 50 eyes in the NE group). The mean ECD was significantly lower in the ACA group than in the other groups (p < 0.001). However, the percentage of ECD reduction was not significantly greater in the ACA group than in the other groups (p > 0.05). None of the eyes developed corneal edema at 3 months postoperatively. Moreover, the CCTs of the three groups were similar throughout the follow-up period (p > 0.05).ConclusionsPhacoemulsification was not associated with greater endothelial cell loss in the ACA group than in the NE and FE groups. This finding shows that ACA history may not contribute to the exacerbation of corneal endothelial damage in cataract surgery.

Accelerated corneal endothelial cell loss in two patients with granulomatosis with polyangiitis following phacoemulsification

BackgroundGenerally, the loss rate of human endothelial cells (HCEC) in routine cataract surgery is 8.5%. When the corneal endothelial cells density (ECD) drops, the HCEC may decompensate to keep cornea dehydration which leads to corneal edema. Granulomatosis with polyangiitis (GPA) is an uncommon autoimmune disease involving multiple organs including eyes such as conjunctivitis, scleritis, uveitis, and corneal ulcer. In this study, we report two cases of GPA whose corneal ECD decreased significantly after phacoemulsification cataract surgery.Case presentationIn the first case of 69-year-old male with GPA, the ECD dropped 39.6% (OD) four months after phacoemulsification and 38.1% (OS) six months postoperatively respectively. At the final follow-up, the residual ECD was only 55% in the right eye in the 49th month, and 56% remained in the left eye in the 39th month. In the second case of 54-year old female, left ECD dropped 63.9% at the 4th month after surgery and 69.6% ECD remained at the 15th month postoperatively while similar ECD of right eye before and after left eye surgery.ConclusionExtensive preoperative ophthalmic evaluation and meticulous postoperative inflammation control should be applied to prevent severe loss of HCEC in GPA patients.

Femtosecond Laser-Assisted Facoemulsification of Hypermature Cataract

Aim. The development and clinical study of optimized femtosecond laser-assisted phacoemulsification (PE) technology of hypermature cataract. Patients and methods. Femtosecond laser-assisted PE of hypermature cataract was performed in 72 patients (72 eyes). The 1st group included 45 patients (45 eyes) who underwent a femtolaser capsulorexis with a pulse power of 6,700 nanojoules (optimized technique for femtosecond laser-assisted РE). The 2nd group included 27 patients (27 eyes) who underwent a femtolaser capsulorexis with a pulse power of 7000 nanojoules. Results. The use of a femtosecond laser to perform anterior capsulorexis in case of PE hypermature cataract is a technique that allows to obtain capsulorexis of an ideal round shape with high diameter accuracy, which is not possible with manual capsulorexis in patients with hypermature cataract. In the 2nd group, radial tear of the edge of capsulorhexis was noted in 2 (7.4 %) cases. In the postoperative period, in all cases in the 1st group, the periphery of the IOL optics was covered with a smooth edge of capsulorhexis of a regular round shape around the entire circumference. In the 2nd group, in 2 (7.4 %) cases, the exit of the edge of the IOL optics from under the edge of the capsulorexis was noted due to its radial tear with the shift of the IOL optics anteriorly, which can negatively affect the accuracy of the refractive result of IOL implantation. Visual acuity without correction and with maximum correction did not have significant differences in both groups and depended on the state of the neuroreceptor apparatus. The average loss of corneal endothelial cells in the 1st group was 5.7 ± 1.4 % and 8.7 ± 1.8 % in the 2nd group (p < 0.05). Conclusion. The use of a femtosecond laser to perform anterior capsulorhexis in PE of hypermature cataract is an effective surgical technique for the treatment of hypermature cataracts, which ensures a fully in-the-bag position of the IOL in the postoperative period . Optimization of the energy parameters of a femtosecond laser helps prevent capsulorexis edge tears in patients with hypermature cataract .

Three-Year Findings of the HORIZON Trial: A Schlemm Canal Microstent for Pressure Reduction in Primary Open-Angle Glaucoma and Cataract

To report 3-year outcomes of the HORIZON study comparing cataract surgery (CS) with Hydrus Microstent (Ivantis, Inc) implantation versus CS alone. Multicenter randomized clinical trial. Five hundred fifty-six eyes from 556 patients with cataract and primary open-angle glaucoma (POAG) treated with 1 or more glaucoma medication, washed out diurnal intraocular pressure (IOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. After phacoemulsification, eyes were randomized 2:1 to receive a Hydrus Microstent or no stent. Follow-up included comprehensive eye examinations through 3 years. Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts. Three hundred sixty-nine eyes were randomized to microstent treatment and 187 to CS only. Preoperative IOP, medication use, washed-out diurnal IOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 mmHg in the microstent group and 17.0 ± 3.4 mmHg in the CS group (P= 0.85). The number of glaucoma medications was 0.4 ± 0.8 in the microstent group and 0.8 ± 1.0 in the CS group (P < 0.001), and 73% of microstent group eyes were medication free compared with 48% in the CS group (P < 0.001). The microstent group included a higher proportion of eyes with IOP of 18 mmHg or less without medications compared with the CS group (56.2% vs. 34.6%; P < 0.001), as well as IOP reduction of at least 20%, 30%, or 40% compared with CS alone. The cumulative probability of incisional glaucoma surgery was lower in the microstent group (0.6% vs. 3.9%; hazard ratio, 0.156; 95% confidence interval, 0.031-0.773; P=0.020). No difference was found in postoperative corneal endothelial cell loss between groups. No procedure- or device-related serious adverse events resulting in vision loss occurred in either group. Combined CS and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtration surgery than CS alone at 3 years.

Fibrillar Layer as a Marker for Areas of Pronounced Corneal Endothelial Cell Loss in Advanced Fuchs Endothelial Corneal Dystrophy

We sought to assess the correlation of corneal endothelial cell (CEC) density to alterations of collagen composition of Descemet membrane (DM) in advanced Fuchs endothelial corneal dystrophy (FECD) and to image such changes by slit-lamp biomicroscopy invivo. Prospective, observational consecutive case series. Fifty eyes (50 subjects) with advanced FECD were enrolled. After slit-lamp biomicroscopy and corneal Scheimpflug imaging, the Descemet endothelium complex (DEC) was retrieved during DM endothelial keratoplasty (DMEK) surgery. The expression of collagens I, III, and IV (COL I, COL III, and COL IV) and corresponding CEC density were analyzed by immunofluorescence flat mount-staining. Presence, diameter and surface area of collagen expression, and CEC density served as the main outcome measures. Immunofluorescence staining revealed central coherent collagen positive areas (mean surface area= 10mm2 ± 6mm2) corresponding to a fibrillar layer burying the guttae of DM in 84% (42/50) of DECs. CEC density overlying the fibrillar layer compared with the periphery was significantly reduced (-54.8%, P< .0001) with a steep decline of CEC density at its borders. Subgroup analysis revealed that the fibrillar layer may be imaged by slit-lamp biomicroscopy invivo with significant positive correlation of mean maximum diameter detected by slit-lamp biomicroscopy (dSL max= 4.1mm ± 0.9mm) and by immunofluorescence staining (dIF max= 4.7mm ± 1.1mm; r= 0.76; P= .001). A fibrillar layer with a clear geographic pattern marks areas of pronounced loss of CEC density in advanced FECD eyes and may be imaged by slit-lamp biomicroscopy invivo.

Application of a prechop technique using a reverse chopper in small pupil cataract surgery.

BackgroundTo analyze the value of a prechop technique for splitting the nucleus of the lens using a reverse chopper in small-pupil cataract surgeries. A prospective case-control study. Thirty-four cataract patients (34 eyes) who were treated in our center from March 2019 to December 2019 were enrolled and then divided into two groups: small pupil group (18 patients; 18 eyes) and normal pupil group (16 patients; 16 eyes).MethodsThe prechop technique was applied in both groups, and the patients were followed up for three months. The best-corrected visual acuity (BVCA), surgical complications, corneal endothelial cell loss, pupil function, operative time, and cumulative dissipated energy (CDE) were compared between these two groups, and the safety of the nucleus-chopping technique was evaluated. Data were analyzed using the SPSS 23.0 software packages. BVCA, surgical complications, rate of corneal endothelial cell loss, pupil function, operative time, and CDE.ResultsThe surgery was smooth in all cases. The operative time, intraoperative ultrasound energy consumption, BVCA, and surgical complications indicated no significant difference between the two groups (all P>0.05). In the small pupil group, BVCA was significantly improved after surgery and achieved its optimal value three months after surgery (χ2=49.38; P=0). The diameter of the pupil was about 3.22 mm in the small pupil group before nucleus chopping. The postoperative pupil morphology was not statistically different from that before surgery (pupil morphology: χ2=0.131; P=0.717); however, the pupillary light reflex was significantly improved after surgery (χ2=8.378; P=0.004), and the pupil diameter was significantly increased (T=−3.494; P=0.003). The rate of corneal endothelial cell loss was higher in small pupil group than in the normal pupil group in the 3rd postoperative month, but the difference was not statistically significant (T=−0.023; P=0.982).ConclusionsThe prechop technique using a reverse chopper in small-pupil cataract surgery occupies a similar operative time, cumulative energy consumption during operation, BVCA, pupil morphology, and rate of corneal endothelial cell loss, comparing with those in normal-pupil cataract surgery. To such a degree, it is a safe, high-efficiency, a simple and easy-to-operate nucleus-chopping technique that can be used in small-pupil cataract surgery.

Effects of ROCK Inhibitors on Apoptosis of Corneal Endothelial Cells in CMV-Positive Posner-Schlossman Syndrome Patients.

PurposeTo examine the role of aqueous tumor necrosis factor α (TNF-α)–RhoA–Rho kinase (ROCK) signaling in cytomegalovirus (CMV)-induced apoptosis and the barrier function of cultured human corneal endothelial cells (hCECs) in CMV-positive Posner–Schlossman syndrome (CMV+/PSS) patients.MethodsAqueous levels of TNF-α, IL-8, IL-10, and several other cytokines in 19 CMV+/PSS patients and 20 healthy control subjects were quantitated using a multiplex assay. The expression of active RhoA in hCECs post-CMV infection was determined using western blotting (WB). The expression levels of TNF-α and nuclear factor kappa B (NF-κB) in CMV-infected hCECs were examined by immunocytochemistry (ICC) and WB with and without ROCK inhibitors. The apoptotic rate and barrier integrity in CMV-infected hCECs were also examined.ResultsThe expression levels of TNF-α, monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-10 were upregulated in the aqueous humor of CMV+/PSS patients, and among these upregulated cytokines aqueous TNF-α was negatively correlated with the number of corneal endothelial cells. In CMV-infected hCECs, upregulation of TNF-α and NF-κB was determined by WB and ICC. In hCECs, CMV infection induced apoptosis and significantly impaired cell–cell contacts, effects that were attenuated by treatment with a ROCK inhibitor.ConclusionsAqueous TNF-α was upregulated in CMV+/PSS patients, which may have triggered corneal endothelial cell loss. Modulation of TNF-α, including its downstream Rho–ROCK signaling, could serve as a novel treatment modality for corneal endothelial cell loss in CMV+/PSS patients.

Determinants of corneal endothelial cell loss after sulcus placement of Ahmed and Baerveldt drainage device surgery

AimIn patients who underwent multiple intraocular surgeries, we evaluated determinants of decreased corneal endothelial cell density (CECD) after sulcus placement following Ahmed and Baerveldt drainage device surgery.MethodsWe retrospectively reviewed consecutive...

Topical anaesthesia plus intracameral lidocaine versus topical anaesthesia alone for phacoemulsification cataract surgery in adults.

Topical anaesthesia plus intracameral lidocaine versus topical anaesthesia alone for phacoemulsification cataract surgery in adults.

Proline-assisted Tube Insertion Through Sulcus in Ahmed Valve.

To prevent corneal endothelial cell loss, ciliary sulcus tube insertion is preferred for the pseudophakic eye. However, we sometimes encounter technical difficulties when inserting the tube through the sulcus. Even in cases in which we are able to insert a 23-G needle through the sulcus into the space between the iris and intraocular lens, the tube of Ahmed valve may stray into the vitreous cavity or under Elschnig pearls. To remedy such conditions, we developed a new tube insertion method using a 4-0 proline stent as a guide to insert the tube in the appropriate position.

Microporous Drug Delivery System for Sustained Anti-VEGF Delivery to the Eye.

PurposeTo describe a novel microporous drug delivery system (DDS) for sustained anti- vascular endothelial growth factor (VEGF) delivery to the eye and to evaluate its efficacy in a corneal injury model.MethodsA macro-porous DDS (1.5 × 1.5 × 4 mm) loaded with 2 mg of bevacizumab was implanted subconjunctivally in three Dutch-belted pigmented rabbits after corneal alkali injury (2N NaOH). Three rabbits received sham DDS. Animals were followed for three months and assessed in vivo and ex vivo for corneal neovascularization (NV), epithelial defect, stromal scarring, endothelial cell loss, and expression of angiogenic and inflammatory markers in the cornea and retina.ResultsAnti-VEGF DDS treatment led to complete inhibition of superior cornea NV and complete corneal re-epithelialization by day 58 whereas sham DDS resulted in severe cornea NV and persistent epithelial defect (9%∼12% of total cornea area) through the end of the study. Histologically, anti-VEGF DDS significantly reduced CD45+ and F4/80 CD11b+ cell accumulation (79%, P < 0.05) in the cornea, ameliorated tumor necrosis factor–α expression (90%, P < 0.05), reduced corneal stromal scarring and prevented corneal endothelial cell loss, as compared to sham DDS. Moreover, anti-VEGF DDS achieved retinal penetration and reduction in retinal VEGF levels at 3 months.ConclusionsUse of subconjunctival anti-VEGF DDS suppresses cornea NV, inflammation, stromal scarring, prevents endothelial cell loss, and abrogates retinal VEGF upregulation in a rabbit corneal alkali burn model. Moreover, it delivers anti-VEGF antibodies to the retina for three months. This delivery platform could enable antibody therapy of other corneal and retinal vascular pathologies.Translational RelevanceWe describe a method for sustained anti-VEGF delivery to the eye for the treatment of ocular injuries.

Longitudinal corneal endothelial cell loss after corrective surgery for late in-the-bag IOL dislocation: a randomized clinical trial.

To compare safety regarding longitudinal corneal endothelial cell loss (ECL) after IOL exchange vs IOL repositioning for late in-the-bag IOL dislocation. Oslo University Hospital, Norway. Prospective, parallel group, randomized clinical trial. During a 3-year period, 104 patients were randomly assigned to groups receiving either IOL exchange with retropupillary fixation of an iris-claw IOL (n = 50) or IOL repositioning by scleral suturing (n = 54). All operations were performed by 1 surgeon with an anterior approach. Endothelial cell density (ECD) and central corneal thickness were measured preoperatively and at 6 months, 1 year, and 2 years postoperatively. A linear mixed model was applied for the longitudinal analysis, where patients with at least 1 ECD measurement were included (n = 44 exchange; n = 50 repositioning). The main outcome measure was 2-year longitudinal ECL in IOL exchange compared with IOL repositioning. The longitudinal ECL was similar between the IOL exchange (n = 44) and IOL repositioning (n = 50) groups during the 2 years of follow-up (17.5% vs 15.3%, P = .15). A subgroup analysis found no reason to advise against either method for patients with low preoperative ECD (<1500 cells/mm). The mean central corneal thickness was similar between the 2 groups and remained stable over 2 years of follow-up. This randomized clinical trial of late in-the-bag IOL dislocation surgery found that exchanging the IOL was as safe as repositioning in terms of 2-year longitudinal ECL.

Histopathological changes in the anterior segment with anterior and posterior chamber intraocular lens

ObjectivePatients have shown a lowering of intraocular pressure (IOP) after cataract surgery. Histopathology studies have reported trabecular meshwork (TM) changes in pseudophakic eyes with posterior chamber intraocular lens (PCIOL) and have eluded to the mechanisms for IOP decrease. Unlike PCIOLs, TM histopathology changes after implantation of an anterior chamber intraocular lens (ACIOL) have not been studied, to our knowledge. Therefore, this study aims to examine the histopathological changes in both the TM and corneal endothelium among donor eyes with ACIOL, PCIOL, and phakic eyes. MethodsForty fixed postmortem donor eyes were obtained, sectioned, and embedded. Slides were stained with Masson's trichrome and CD31 vascular endothelial antibody, and further digitalized. Customized Medical Parachute TMAN software quantified the cellular components, the trabecular extracellular matrix (ECM), ECM fibrosis, and trabecular area. Schlemm's canal and corneal endothelium were quantified across the ACIOL, PCIOL, and phakic groups. ResultsCellular area component of the TM was lower in the ACIOLs and PCIOLs than in phakic eyes, but statistically significant only between PCIOL and phakic eyes (p = 0.0023). ECM area component, TM fibrosis score and TM lamellae area, ciliary process fibrosis, and CD31 expression in Schlemm's canal showed no differences (p = 0.40, 0.99, 0.10, 0.83, 0.45). Significantly lower corneal endothelial cells were seen in ACIOLs compared with both PCIOLs and phakic eyes (p = 0.0002). ConclusionsACIOLs and PCIOLs in our sample group showed that there is loss of cellular components in the TM compared with the phakic eyes, with PCIOLs displaying the least amount of TM cells statistically, in this cohort. The ACIOLs led to a greater loss of corneal endothelial cells than both PCIOLs and phakic eyes after cataract surgery. The endothelial cells in Schlemm's canal did not seem to be affected by the IOL placements. Therefore, this study illustrates that there are histopathological differences seen with the placements of ACIOLs in both TM and cornea.

Phase 3, Randomized, 20-Month Study of Bimatoprost Implant in Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 1)

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations. Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout. Study eyes received bimatoprost implant 10 μg (n= 198) or 15 μg (n= 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n= 198). Intraocular pressure was measured at hours 0 and 2 at each visit. Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit. Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.

Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice.

Corneal endothelial cell (CEnC) loss after corneal transplantation is the major cause of graft failure and remains a clinically relevant challenge to overcome. Accumulated knowledge derived from long-term clinical outcomes suggested that elevated protein levels in the aqueous humor are associated with CEnC loss. However, the full spectrum of driver proteins and molecular processes remains to be determined. Here, we defined the somatic microenvironmental landscape and cellular response across human aqueous humor in samples with poor corneal transplantation clinical outcomes using multiomics analyses and clarified specific driver alterations, including complement activation and disturbed energy homeostasis. These driver alterations were also confirmed in aqueous humor from a novel murine model that spontaneously develops iris atrophy, leading to CEnC loss. The application of the integrative multiomics performed in human samples to the novel murine model will help the development of therapeutic modalities for patients with CEnC loss after corneal transplantation.

Explantation of the CyPass implant in acase series of patients with corneal decompensation

In microinvasive glaucoma surgery (MIGS) the CyPass microstent (Alcon Inc.) was implanted in the suprachoroidal space to increase the uveoscleral outflow, thereby lowering the intraocular pressure. Due to the excessive loss of corneal endothelial cells, the implant was withdrawn from the global market in August 2018. Aloss of corneal endothelial cells was observed in 6patients (8eyes in total) with early to moderate primary open-angle glaucoma 3years after CyPass implantation. One eye developed abullous keratopathy. In all patients an implant migration in the anterior chamber compared to the original postoperative position was detected, with more than one ring of the CyPass implant being visible in the anterior chamber. In all eight cases the CyPass implant was removed. The local therapy with cortisone eye drops in combination with a5% sodium chloride solution did not improve chronic corneal edema in one patient. Therefore, aDescemet membrane endothelial keratoplasty (DMEK) was performed with postoperative improvement of visual acuity. In patients with more than one visible ring of the CyPass implant in the anterior chamber and subsequent localized loss of corneal endothelial cells, CyPass trimming or removal is recommended to avoid the progression of generalized corneal endothelial cell reduction and the onset of refractory, chronic corneal edema.