[Impact of the ratio between graft and host corneal size on immune rejection, re-bubbling rate and postoperative endothelial cell loss in 457 eyes after Descemet membrane endothelial keratoplasty (DMEK)]. / Einfluss des Verhältnisses von Transplantatgröße zu Hornhautgröße auf Immunreaktion, Re-Bubbling-Rate und postoperativen Endothelzellverlust bei 457 Augen nach Descemet-Membrane-Endothelial-Keratoplastik (DMEK).

BACKGROUND: The aim of this study was to assess the impact of the ratio between the graft and host corneal size (RGH) on postoperative complications, such as immune reactions, re-bubbling rate and endothelial cell loss (ECL) after Descemet membrane endothelial keratoplasty (DMEK). PATIENTS AND METHODS: Retrospectively, 457 patient eyes were included which had undergone surgery between 2016 and 2019 in the Department of Ophthalmology, Saarland University Medical Center in Homburg/Saar using DMEK or triple DMEK, diagnosed as Fuchs' endothelial dystrophy (n = 431), pseudophakic bullous keratopathy (n = 9) and others (n = 17). The follow-up period extended until the end of 2020. Main outcome measures included immune reaction (IR), re-bubbling rate and the postoperative endothelial cell loss (ECL) at 6 weeks, 6 months and 12 months and whether these measures depended on the RGH. RESULTS: The RGH in this study ranged from 0.35 to 0.62 (0.46 ± 0.04). There were 33 (7.2%) postoperative IRs (DMEK n = 25; triple DMEK n = 8). The average RGH without IR (0.46 ± 0.04) was significantly (p = 0.038) smaller than in the group with IR (0.47 ± 0.05). Re-bubbling was necessary in 159 of 457 (34.8%) patient eyes. The RGH in patient eyes with re-bubbling (0.47 ± 0.04) was significantly (p = 0.014) higher than that in eyes without re-bubbling (0.45 ± 0.04). The mean preoperative endothelial cell count (ECD) was 2603 ± 251 cells/mm2 (min: 2161, max: 3500 cells/mm2). It was shown that a larger RGH had no positive influence on endothelial cell loss (r = 0.001; p = 0.974). CONCLUSION: Our results suggest that a larger graft diameter compared to host corneal size is associated with an increased rate of immune reactions and a higher re-bubbling rate after DMEK. Otherwise, a larger RGH had no positive influence on endothelial cell loss after DMEK. Accordingly, the graft size for DMEK should not be unnecessarily large, especially in eyes with Fuchs' endothelial dystrophy.

Narrative review after post-hoc trial analysis of factors that predict corneal endothelial cell loss after phacoemulsification: Tips for improving cataract surgery research.

PURPOSE: Identifying pre/perioperative factors that predict corneal endothelial-cell loss (ECL) after phacoemulsification may reveal ways to reduce ECL. Our literature analysis showed that 37 studies have investigated one or several such factors but all have significant limitations. Therefore, the data of a large randomized controlled trial (PERCEPOLIS) were subjected to post-hoc multivariate analysis determining the ability of nine pre/perioperative variables to predict ECL. METHODS: PERCEPOLIS was conducted in 2015-2016 to compare two phacoemulsification techniques (subluxation and divide-and-conquer) in terms of 3-month ECL. Non-inferiority between the techniques was found. In the present study, post-hoc univariate and multivariate analyses were conducted to determine associations between ECL and age, sex, cataract density, preoperative endothelial-cell density, phacoemulsification technique, effective phaco time (EPT), and 2-hour central-corneal thickness. The data are presented in the context of a narrative review of the literature. RESULTS: Three-month data were available for 275 patients (94% of the randomized cohort; mean age, 74 years; 58% women). Mean LOCSIII cataract grade was 3.2. Mean EPT was 6 seconds. Mean ECL was 13%. Only an older age (beta = 0.2%, p = 0.049) and higher EPT (beta = 1.2%, p = 0.0002) predicted 3-month ECL. Cataract density was significant on univariate (p = 0.04) but not multivariate analysis. The other variables did not associate with ECL. CONCLUSIONS: Older age may amplify ECL due to increased endothelial cell fragility. EPT may promote ECL via cataract density-dependent and -independent mechanisms that should be considered in future phacoemulsification research aiming to reduce ECL. Our literature analysis showed that the average ECL for relatively unselected consecutively-sampled cohorts is 12%.

Corneal endothelial cell loss and intraocular pressure following phacoemulsification using a new viscous-cohesive ophthalmic viscosurgical device.

PURPOSE: To compare results of two ophthalmic viscosurgical devices (OVDs)-Viscoat (a dispersive OVD, Alcon) and FR-Pro (a viscous-cohesive OVD, Rayner), in phacoemulsification surgery. METHODS: A prospective randomized controlled study. Patients undergoing phacoemulsification were randomly assigned to receive one of the two OVDs. Exclusion criteria were age under 40, preoperative endothelial cell count (ECC) below 1,500 cells/mm2 and an eventful surgery. The primary outcome was change in ECC from baseline to postoperative month one and month three. Secondary outcomes were the difference between ECC at postoperative month one and month three, changes in IOP and occurrence of an IOP spike ≥ 30 mmHg after surgery. RESULTS: The study included 84 eyes-43 in the Viscoat group and 41 in the FR-Pro group. Mean cell density loss at month one and month three was 17.0 and 19.2%, respectively, for the Viscoat group and 18.4 and 18.8%, respectively, for the FR-Pro group, with no statistically significant difference between the groups (p = 0.772 and p = 0.671, respectively). The mean ECC difference between the month one and month three visits was 50.5 cells/mm2 and was not statistically significant (p = 0.285). One eye in each group had an IOP spike ≥ 30 mmHg, both normalized by postoperative week one. CONCLUSIONS: Viscoat and FR-Pro have comparable results following phacoemulsification surgery, suggesting that while FR-Pro is not a dispersive OVD, its endothelial cell protection may be comparable to one, perhaps due to the addition of sorbitol. Furthermore, a one-month follow-up of ECC seems sufficient in such trials.

Changes in endothelial cell density after conventional phacoemulsification and FLACS in eyes with dense cataracts.

PURPOSE: To compare the safety, effectiveness, and changes in endothelial cell density (ECD) after standard phacoemulsification and femtosecond laser-assisted cataract surgery (FLACS) in dense cataracts (Lens Opacities Classification System III grade 3.0 NO and above). SETTING: Nethradhama Superspeciality Eye Hospital, Bangalore, India. DESIGN: Prospective, randomized, comparative study. METHOD: 100 eyes of 100 patients were randomly assigned to either conventional phacoemulsification surgery (CPS) or FLACS (LENSAR Laser System) using predefined patterns of nuclear fragmentations. Measured outcomes included intraoperative phacoemulsification time, irrigation fluid volume, surgical time, and complication rates. ECD was evaluated at baseline, 2 weeks, and 6 months postoperatively. RESULTS: The CPS group had significantly higher mean total phacoemulsification time (11.17 ± 6.5 seconds vs 8.03 ± 3.77 seconds), effective phacoemulsification time (6.14 ± 3.62 seconds vs 4.42 ± 2.07 seconds), and total surgical time (8.18 ± 2.36 minutes vs 7.11 ± 1.55 minutes) than the FLACS group ( P < .001). Volume of irrigation fluid was comparable between the 2 groups (CPS, 36.7 ± 12.18 mL; FLACS, 38.64 ± 13.73 mL ( P = .45). Mean corneal edema score and central corneal thickness values on postoperative day 1 were significantly higher for the CPS group. At 6 months, % ECD loss was significantly higher in the CPS group (16.08%) vs the FLACS group (12.8%) ( P < .001). 3 eyes in the CPS group had wound burns of varying severity. CONCLUSIONS: FLACS with customized nuclear fragmentation patterns resulted in significantly less intraoperative phacoemulsification time, surgical time, and endothelial cell loss compared with conventional phacoemulsification when treating dense cataracts. TRIAL REGISTRATION NUMBER: CTRI/2021/12/038887.

Corneal endothelial cell loss after EX-PRESS surgery depends on site of insertion, cornea or trabecular meshwork.

PURPOSE: Previously, we reported that the Ex-press® shunt (EXP) was associated with more rapid reduction in corneal endothelial cells when inserted into the cornea rather than the trabecular meshwork (TM). We compared the reduction rate of corneal endothelial cells between the corneal insertion group and TM insertion group. METHODS: This was a retrospective study. We included patients who had undergone EXP surgery and were followed for > 5 years. We analyzed the corneal endothelial cell density (ECD) before and after EXP implantation. RESULTS: We included 25 patients in the corneal insertion group and 53 patients in the TM insertion group. One patient in the corneal insertion group developed bullous keratopathy. The ECD decreased significantly more rapidly in the corneal insertion group (p < 0.0001), in whom the mean ECD decreased from 2227 ± 443 to 1415 ± 573 cells/mm2 at 5 years with a mean 5-year survival rate of 64.9 ± 21.9%. By contrast, in the TM insertion group, the mean ECD decreased from 2356 ± 364 to 2124 ± 579 cells/mm2 at 5 years, and the mean 5-year survival rate was 89.3 ± 18.0%. The decrease rate of ECD was calculated as 8.3%/year in the corneal insertion group and 2.2%/year in the TM insertion group. CONCLUSIONS: Insertion into cornea is a risk factor for rapid ECD loss. The EXP should be inserted into the TM to preserve the corneal endothelial cells.

Different patterns in the corneal endothelial cell loss after pars plana and pars limbal insertion of the Baerveldt glaucoma implant.

PURPOSE: To assess corneal endothelial cell (CE) loss after pars plana (PP) and pars limbal (PL) insertion of a Baerveldt glaucoma implant (BGI). DESIGN: Retrospective multicenter interventional comparative study. METHODS: We studied central CE loss for 5 years after BGI surgery in 192 eyes. RESULTS: The prevalence of bullous keratopathy (BK) was greater in the PL cohort than in the PP cohort (P = .003). The CE loss after simultaneous PP vitrectomy and tube insertion into the vitreous cavity was 11.9% in the first year, which was greater than that of 2.9% in eyes where the tube was inserted simply into the vitreous cavity after a prior vitrectomy (P = .046). The annual percentage CE loss after the first year decreased unidirectionally in both of those groups and was 1.3% and 1.0% in the fifth year, respectively (P < .001). For limbal insertion, the CE loss in the simple PL cohort was biphasic, decreasing from 10.5% in the first year to 7.0% in the fifth year. Simultaneous cataract and BGI surgery enhanced the CE loss slightly in the first year in the PP and PL cohorts to 13.0% and 14.0%, respectively. However, these increases were not significant (P = .816 and .358, respectively). Low preoperative CE density (P < .001) and insertion site (P = .020) were significant risk factors for the development of BK. CONCLUSIONS: CE loss in the PL and PP cohorts was biphasic and unidirectional, respectively. The difference in annual CE loss became evident over time. PP tube implantation may be advantageous when the preoperative CE density is low.

Comparison of corneal endothelial cell loss during manual small-incision cataract surgery using viscoelastic-assisted nucleus removal versus continuous balanced salt solution plus technique - Randomized controlled trial.

Purpose: The purpose of this study was to compare and analyze the endothelial cell loss during manual small-incision cataract surgery (MSICS) using the viscoelastic-assisted nucleus removal versus basal salt solution plus technique. Methods: This was a prospective randomized trial of 204 patients who underwent MSICS using viscoelastic-assisted nucleus removal (Group 1- OVD) versus basal salt solution plus technique (Group 2- BSS) at a tertiary eye care hospital in North India from January 2018 to 2021. Of these 204 patients, 103 (50.5%) and 101 (49.5%) were allocated to Group 1 and 2, respectively. The parameters assessed were detailed history, demographics, and anterior and posterior segment details. Visual acuity, intraocular pressure (IOP), keratometry, pachymetry, and endothelial cell density were evaluated preoperatively and postoperatively on day 1 and 30. Results: The mean age of the patients was 64.5 ± 8.2 years (range 48-82 years). There were 129 (63.2%) males and 75 (36.8%) females. The mean LogMAR visual acuity for both groups on day 1 (Group 1- 0.3 ± 0.1, Group 2- 0.5 ± 0.2) and day 30 (Group 1- 0.1 ± 0.2, Group 2- 0.1 ± 0.1) was statistically significant (P < 0.001), and the mean IOP value showed a statistically significant value (P < 0.009) on day 1 in Group 2 (15.0 ± 2.4 mmHg) and on day 30 (P < 0.001) in both the groups (Group 1- 13.6 ± 1.8 mmHg, Group 2- 13.5 ± 2 mmHg). The horizontal and vertical k values also showed a statistically significant difference on day 1 and day 30 (P < 0.001). The mean percentage change of central corneal thickness (CCT) in Group 1 was 17.7% and in Group 2 was 17.4% on day 1, and it was 1.1% on day 30 in both the groups, which was statistically significant (P < 0.001) compared to preoperative values. The percentage change in endothelial cell density on day 1 was 9% in Group 1 and 4.6% in Group 2, which was statistically significant (P < 0.001). On day 30, it was 9.7% and 4.8%, respectively, which was statistically significant (P < 0.001). Conclusion: Our study highlights statistically significant endothelial cell loss with viscoelastic-assisted nuclear delivery compared to BSS-assisted nuclear delivery during MSICS in a short follow-up of 1 month. The CCT values showed a slight increase, and the keratometry and IOP were unaffected compared to the preoperative parameters in both the groups.

Corneal Endothelial Cell Density Loss after Glaucoma Surgery Alone or in Combination with Cataract Surgery: A Systematic Review and Meta-analysis.

TOPIC: Corneal endothelial cell density (ECD) loss after glaucoma surgery with or without cataract surgery. CLINICAL RELEVANCE: Corneal ECD loss may occur as the result of intraoperative surgical trauma in glaucoma surgery or postoperatively with chronic endothelial cell trauma or irritation. METHODS: Glaucoma filtration surgery or microinvasive glaucoma surgery (MIGS) in participants with ocular hypertension, primary and secondary open-angle glaucoma, normal-tension glaucoma, and angle-closure glaucoma were included. Electronic databases searched in December 2021 included MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the International Prospective Register of Systematic Reviews, Food and Drug Administration (FDA) Premarket Approval, and FDA 510(k). RESULTS: A total of 39 studies were included in quantitative synthesis. Twelve months after suprachoroidal MIGS, mean ECD loss was 282 cells/mm2 (95% confidence interval [CI], 220-345; P < 0.00001; chi-square = 0.06; I2 = 0%; 2 studies; very low certainty). Mean ECD loss after Schlemm's canal implantable devices was 338 cells/mm2 (95% CI, 185-491; P < 0.0001; chi-square = 0.08; I2 = 0%; 2 studies; low certainty) at 12 months. Mean ECD loss was 64 cells/mm2 (95% CI, 21-107; P = 0.004; chi-square = 4.55; I2 = 0%; 6 studies; low certainty) after Schlemm's canal procedures (without implantable devices) at 12 months. At 12 months, the mean ECD loss after trabeculectomy was 33 cells/mm2 (95% CI, -38 to 105, P = 0.36, chi-square = 1.17; I2 = 0%; moderate certainty). At 12 months, mean ECD loss was 121 cells/mm2 (95% CI, 53-189; P = 0.0005; chi-square = 3.00; I2 = 0%; 5 studies; low certainty) after Express (Alcon) implantation. When compared with the control fellow eye, aqueous shunt surgery reduced ECD by 5.75% (95% CI, -0.93 to 12.43; P = 0.09, chi-square = 1.32; I2 = 0%; low certainty) and 8.11% ECD loss (95% CI, 0.06-16.16 P = 0.05; chi-square = 1.93; I2 = 48%) at 12 and 24 months, respectively. CONCLUSIONS: Overall, there is low certainty evidence to suggest that glaucoma surgery involving long-term implants has a greater extent of ECD loss than glaucoma filtration surgeries without the use of implants. The results of this review support follow-up beyond 36 months to assess ECD loss and corneal decompensation after implantation of glaucoma drainage implants.

Graft survival of Descemet membrane endothelial keratoplasty (DMEK) in corneal endothelial decompensation after glaucoma surgery.

PURPOSE: This study aims to assess the results, rebubbling rate, and graft survival after Descemet membrane endothelial keratoplasty (DMEK) with regard to the number and type of previous glaucoma surgeries. METHODS: This is a clinical retrospective review of 1845 consecutive DMEK surgeries between 07/2011 and 08/2017 at the Department of Ophthalmology, University of Cologne. Sixty-six eyes were included: group 1 (eyes with previous glaucoma drainage devices (GDD); n = 27) and group 2 (eyes with previous trabeculectomy (TE); n = 39). Endothelial cell loss (ECL), central corneal thickness, graft failure, rebubbling rate, and best spectacle-corrected visual acuity (BSCVA) up to 3 years after DMEK were compared between subgroups of patients with different numbers of and the two most common types of glaucoma surgeries either GDD or TE or both. RESULTS: Re-DMEK rate due to secondary graft failure was 55.6% (15/27) in group 1 and 35.9% in group 2. The mean graft survival time in group 1 was 25 ± 11 months and 31.3 ± 8.6 months in group 2 (p = 0.009). ECL in surviving grafts in group 1 was 35% (n = 13) at 6 months, 36% at 12 months (n = 8), and 27% (n = 4) at 2 years postoperatively. In group 2, ECL in surviving grafts was 41% (n = 10) at 6 months, 36% (n = 9) at 12 months, and 38% (n = 8) at 2 years postoperatively. Rebubbling rate in group 1 was 18.5% (5/27) and 35.9% (14/39) in group 2 (p = 0.079). CONCLUSION: Eyes with previous GDD had no higher risk for an increased rebubbling rate but a higher risk for a re-DMEK due to secondary graft failure with a mean transplant survival time of about 2 years. Compared to eyes with preexisting glaucoma drainage device, eyes after trabeculectomy had less secondary graft failures and a longer mean graft survival rate.

The long-term postoperative effect of the Baerveldt glaucoma drainage device and of a trabeculectomy on the corneal endothelium.

PURPOSE: To determine whether the postoperative corneal endothelial cell density (ECD) differs between glaucoma patients who underwent Baerveldt implant (BGI) surgery and patients who underwent a trabeculectomy (TE) over 5 years ago. METHODS: Cross-sectional, observational study including 34 patients who underwent TE and 36 patients who underwent BGI surgery 5-11 years ago, as part of a randomized clinical trial. None of the patients had a history of intraocular surgery prior to their glaucoma surgery. Central and peripheral ECD was measured by using a non-contact specular microscope. RESULTS: Central and peripheral ECD in the TE group was 2285 ± 371 cells/mm2 (mean ± SD) and 2463 ± 476 cells/mm2 , respectively. Central and peripheral ECD in the BGI group was 1813 ± 745 cells/mm2 and 1876 ± 764 cells/mm2 , respectively. The central and peripheral ECD was statistically significantly higher in the TE group than in the BGI group (p = 0.001 for both). Additional intraocular surgical interventions were more prevalent in the BGI group (23) than in the TE group (5) (p < 0.001). In a subanalysis, without eyes that had undergone additional surgical interventions, only the peripheral ECD was statistically significantly higher in the TE group compared with the BGI group (p = 0.011). For the BGI group, a longer postoperative period resulted in a lower central ECD (r = -0.614, p = 0.004). CONCLUSION: Long-term ECD in eyes that underwent a BGI was considerably lower compared with eyes that underwent a TE, mainly in the peripheral cornea. This suggests that BGI causes a larger decrease of ECD than TE. Additionally, the decrease after BGI appears to continue for a longer period than after TE.

Corneal endothelial cell damage after scleral fixation of intraocular lens surgery.

PURPOSE: To analyze corneal endothelial cell damage after scleral fixation of intraocular lens (SFIOL) surgery. STUDY DESIGN: Retrospective study. METHODS: Medical records of consecutive eyes undergoing SFIOL surgery performed by a single surgeon were reviewed between January 2011 and June 2019. The patients were classified into three groups according to surgical methods: Group I, re-fixating the existing intraocular lens (IOL) or fixating a new IOL in an aphakic eye; Group II, removing the existing IOL and fixating a new IOL; and Group III, phacoemulsification and fixating a new IOL simultaneously. Preoperative and postoperative specular microscopy (SM) status were compared. Changes in SM were compared among the three groups. RESULTS: Ninety-four eyes were included. Thirty-four eyes in Group I, 39 in Group II, and 21 in Group III. The endothelial cell density (ECD) loss in Group I was 1.5%, less than the ECD loss of 14.3% (p < 0.001) in Group II and 15.4% (p = 0.005), in Group III. In no eye was there an ECD decrease to < 1000/mm2 following the surgical procedure. CONCLUSIONS: ECD loss was related to IOL removal or phacoemulsification rather than SFIOL surgery. SFIOL using the existing IOL should be considered preferential in eyes with low ECD and dislocated IOL.

Association between aqueous humor cytokines and postoperative corneal endothelial cell loss after Descemet stripping automated endothelial keratoplasty.

This study measured the intraoperative anterior aqueous humor concentrations of various cytokines during corneal endothelial transplantation and searched for relationships between these concentrations and postoperative corneal endothelial cell (CEC) depletion. We recruited 30 consecutive patients who underwent corneal endothelial transplantation with Descemet's stripping automated endothelial keratoplasty (DSAEK) at Tohoku University Hospital between February 2014 and July 2017. During surgery, we obtained aqueous humor samples and later measured the concentrations of 27 cytokines with a Multiplex Bead Assay (Bio-Plex Pro). We counted CECs 1, 6 and 12 months after surgery, and used Spearman's rank correlation coefficient to identify relationships between CEC depletion and the concentrations of detected cytokines. The loss of CECs 1-6 months after surgery was significantly correlated with IL-7, IP-10, MIP-1a and MIP-1b concentrations (-0.67, -0.48, -0.39, and -0.45, respectively, all P <0.01). CEC loss 1-12 months after surgery was significantly correlated with IL-1b, IL-7, IP-10 and RANTES concentrations (-0.46, -0.52, -0.48, and -0.43, respectively). Multiple regression analysis showed that IL-7 concentration was significantly associated with CEC loss 1-6 months after surgery (b = -0.65, P < 0.01) and IP-10 concentration was associated with CEC loss 1-12 months after surgery (ß = -0.38, P < 0.05). These results suggest that not only inflammatory cytokines but also IL-7, a cytokine related to lymphocytes, may be involved in the depletion of CECs after DSAEK, particularly depletion that occurs relatively early.

Ab interno supraciliary microstent surgery for open-angle glaucoma.

BACKGROUND: Glaucoma is the leading cause of global irreversible blindness, often associated with raised intraocular pressure (IOP). Where medical or laser treatment has failed or is not tolerated, surgery is often required. Minimally-invasive surgical approaches have been developed in recent years to reduce IOP with lower surgical risks. Supraciliary microstent surgery for the treatment of open-angle glaucoma (OAG) is one such approach. OBJECTIVES: To evaluate the efficacy and safety of supraciliary microstent surgery for the treatment of OAG, and to compare with standard medical, laser or surgical treatments. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2020, Issue 8); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 27 August 2020. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of supraciliary microstent surgery, alone or with cataract surgery, compared to other surgical treatments (cataract surgery alone, other minimally invasive glaucoma device techniques, trabeculectomy), laser treatment or medical treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts from the database search to identify studies that met the selection criteria. Data extraction, analysis, and evaluation of risk of bias from selected studies was performed independently and according to standard Cochrane methodology. MAIN RESULTS: One study met the inclusion criteria of this review, evaluating the efficacy and safety of the Cypass supraciliary microstent surgery for the treatment of OAG, comparing phacoemulsification + supraciliary microstent surgery with phacoemulsification alone over 24 months. This study comprised 505 eyes of 505 participants with both OAG and cataract, 374 randomised to the phacoemulsification + microstent group.  In this study, the perceived risk of bias from random sequence generation, allocation concealment and selective reporting was low. However, we considered the study to be at high risk of performance bias as surgeons/investigators were unmasked. Attrition bias was unclear, with 448/505 participants contributing to per protocol analysis. Insertion of a Cypass supraciliary microstent combined with phacoemulsification probably increases the proportion of participants who are medication-free (not using eye-drops) at 24 months compared with phacoemulsification alone (85% versus 59%, risk ratio (RR) 1.27, 95% confidence interval (CI) 1.09 to 1.49, moderate-certainty evidence). There is high-certainty evidence that a greater improvement in mean IOP occurs in the phacoemulsification + microstent group - mean (SD) change in IOP from baseline of -5.4 (3.9) mmHg in the phacoemulsification group, compared to -7.4 (4.4) mmHg in the phacoemulsification + microstent group at 24 months (mean difference -2.0 mmHg, 95% CI -2.85 to -1.15). There is moderate-certainty evidence that insertion of a microstent is probably associated with a greater reduction in use of IOP-lowering drops (mean reduction of 0.7 medications in the phacoemulsification group, compared to a mean reduction of 1.2 medications in the phacoemulsification + microstent group). Insertion of a microstent during phacoemulsification may reduce the requirement for further glaucoma intervention to control IOP at a later stage compared to phacoemulsification alone (RR 0.26, 95% CI 0.07 to 1.04, low-certainty evidence). There is no evidence relating to the rate of visual field progression, or proportion of participants whose visual field loss progressed in this study. There is moderate-certainty evidence showing little or no difference in the proportion of participants experiencing postoperative complications over 24 months between participants in the microstent group compared to those who received phacoemulsification alone (RR 1.1, 95% CI 0.8 to 1.4). Five year post-approval data regarding the safety of the Cypass supraciliary microstent showed increased endothelial cell loss, associated with the position of the microstent in the anterior chamber. There were no reported health-related quality of life (HRQoL) outcomes in the included study. AUTHORS' CONCLUSIONS: Data from this single RCT show superiority of supraciliary microstent surgery when combined with phacoemulsification compared to phacoemulsification alone in achieving medication-free control of OAG. However, there are long-term safety concerns with the device used in this trial, relating to the observed significant loss of corneal endothelial cells at five years following device implantation. At the time of this review, this device has been withdrawn from the market. This review has found that few high-quality studies exist comparing supraciliary microstent surgery to standard medical, laser or surgical glaucoma treatments. This should be addressed by further appropriately designed RCTs with sufficient long-term follow-up to ensure robust safety data are obtained. Consideration of health-related quality of life outcomes should also feature in trial design.

Cigarette Smoke Triggers Loss of Corneal Endothelial Cells and Disruption of Descemet's Membrane Proteins in Mice.

Purpose: To investigate changes at a molecular level in the mouse corneal endothelium (CE) exposed to chronic cigarette smoke (CS). Methods: Pregnant mice (gestation days 18-20) were placed in a whole-body exposure smoking chamber, and a few days later pups were born. After 3.5 months of CS exposure, a ConfoScan4 scanning microscope was used to examine the corneal endothelial cells (CECs) of CS-exposed and control (Ct) mice. The CE was peeled under a microscope and maintained as four biological replicates (two male and two female) for CS-exposed and Ct mice; each replicate consisted of 16 CEs. The proteome of the CE was investigated through mass spectrometry. Results: The CE images of CS-exposed and Ct mice revealed a difference in the shape of CECs accompanied by a nearly 10% decrease in CEC density (P < 0.00003) following CS exposure. Proteome profiling identified a total of 524 proteins exhibiting statistically significant changes in CE from CS-exposed mice. Importantly, proteins associated with Descemet's membrane (DM), including COL4α1, COL4α2, COL4α3, COL4α4, COL4α5, COL4α6, COL8α1, COL8α2, and FN1, among others, exhibited diminished protein levels in the CE of CS-exposed mice. Conclusions: Our data confirm that exposure to CS results in reduced CEC density accompanied by diminished levels of multiple collagen and extracellular matrix proteins associated with DM.

Descemet Membrane Endothelial Keratoplasty versus Descemet Stripping Automated Endothelial Keratoplasty in Complicated Vitrectomized Eyes.

PURPOSE: Vitrectomized eyes pose a technical challenge when performing endothelial keratoplasty (EK). The aim of the study was to compare outcomes of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in complex eyes undergoing pars plana vitrectomy (PPV) prior to or during surgery. METHODS: This retrospective study included consecutive eyes that underwent pars plana infusion-assisted DMEK or pull-through DSAEK which underwent PPV prior to or during the EK at a tertiary center. Included were eyes with at least 1-year follow-up. The main outcome measures were best-corrected visual acuity (BCVA) and serious adverse events. RESULTS: Fifty-two eyes (n = 52) with a mean follow-up time of 24.6 ± 7.4 months were included. Both groups were similar in terms of baseline characteristics although the DMEK group had a significantly larger proportion of Fuchs' patients (p = .009). There was no significant difference in postoperative logMAR BCVA between groups at each visit (p > .05 for all). There was a significantly higher proportion of overall serious adverse events (50.0% versus 15.4%, p = .02), retinal detachments (19.2% versus 0.0%, p = .05) and cystoid macular edema (23.1% versus 0.0%, p = .02) following DMEK. Graft detachment occurred more often following DMEK (53.9% versus 11.5%, p = .001) with no significant difference in rebubbling rates (23.1% versus 11.5%, p = .27). CONCLUSIONS: A significant and similar improvement in BCVA was achieved following DMEK and DSAEK in complex vitrectomized eyes. Patients should be advised regarding the higher rates of potential serious complications associated with a pars plana infusion DMEK in this situation.

Risk Factors for Repeat Descemet Membrane Endothelial Keratoplasty Graft Failure.

PURPOSE: To evaluate repeat Descemet membrane endothelial keratoplasty (re-DMEK) success rates and to identify risk factors for re-DMEK failure. DESIGN: Retrospective case series. METHODS: Settings: Institutional. PATIENTS AND INTERVENTIONS: A chart review was performed, including all eyes with primary DMEK failure that underwent re-DMEK between 2013 and 2019 at the Toronto Western Hospital and the Kensington Eye Institute (Toronto, Ontario, Canada) and had at least 6 months of follow-up. MAIN OUTCOME MEASURE: Predicting factors for re-DMEK outcome. RESULTS: Of 590 consecutive DMEK surgeries, 40 eyes (6.7%) were identified for having a secondary DMEK surgery after primary DMEK failure. Etiologies for primary DMEK were Fuchs endothelial corneal dystrophy (32.5%), pseudophakic bullous keratopathy (35%), previous failed graft (27.5%), and other indications (5%). Fifty-five percent of the cohort were categorized as having a complicated anterior segment including 11 eyes with previous glaucoma surgery, 7 eyes post-penetrating keratoplasty, 4 eyes post-Descemet stripping automated endothelial keratoplasty, 3 eyes peripheral anterior synechia, 3 eyes previous pars plana vitrectomy, 2 eyes aphakia, and 1 eye each with aniridia, anterior chamber intraocular lens, and iris-fixated intraocular lens. Re-DMEK failure was documented in 12 eyes (30%) of the entire cohort. The risk factor for re-DMEK failure was the presence of a complicated anterior segment (P = .01, odds ratio = 17.0 [95% confidence interval: 1.92-150.85]), with 50% re-DMEK failure rate in this subgroup. CONCLUSION: Re-DMEK is a viable option for cases of primary DMEK failure, especially for eyes with Fuchs endothelial corneal dystrophy as the indication for primary DMEK without other ocular morbidities; however, eyes categorized with a complicated anterior segment had high re-DMEK failure rates..

Corneal endothelial cell loss after trabeculectomy and phacoemulsification in one or two steps: a prospective study.

OBJECTIVE: The objective of this study was to analyse the results of the surgical treatment of coexisting cataract and glaucoma and its effects on corneal endothelial cell density (CECD). METHODS: We include two longitudinal prospective studies: one randomised that included 40 eyes with open angle glaucoma that received one- (n = 20) or two-step (n = 20) phacotrabeculectomy and another that included 20 eyes that received phacoemulsification. We assess the impact of surgery on different clinical variables and in particular in CECD using Confoscan 4™ confocal microscopy and semiautomatic counting methods. RESULTS: Phacoemulsification and phacotrabeculectomy, but not trabeculectomy, increase significantly best-corrected visual acuity and anterior chamber depth and trabeculectomy and one- or two-step phacotrabeculectomy decreased similarly the intraocular pressure. We document percentages of endothelial cell loss of 3.1%, 17.9%, 31.6% and 42.6% after trabeculectomy, phacoemulsification and one- or two-step phacotrabeculectomy, respectively. The coefficient of variation did not increase significantly after surgery but the percentage of hexagonality decreased significantly after phacoemulsification and after two-step phacotrabeculectomy. CONCLUSIONS: Trabeculectomy, phacoemulsification and phacotrabeculectomy are surgical techniques that cause morphological changes and decrease the densities of the corneal endothelial cells. Trabeculectomy produces lesser endothelial cell loss than phacoemulsification, and phacoemulsification lesser cell loss than phacotrabeculectomy. Two-step phacotrabeculectomy (trabeculectomy followed 3 months later by phacoemulsification) causes more cell loss than one-step phacotrabeculectomy, and this could be due to the cumulative effects of two separate surgical traumas or to a negative conditioning lesion effect of the first surgery. For the treatment of coexisting glaucoma and cataract, one-step phacotrabeculectomy is the treatment of choice.

XEN Gel Stent versus trabeculectomy: Short-term effects on corneal endothelial cells.

PURPOSE: To compare the short-term changes in corneal endothelial cells after trabeculectomy or XEN Gel Stent implantation. DESIGN: Prospective, interventional, comparative study. METHODS: Changes in corneal endothelium in patients that underwent XEN Gel Stent implantation or trabeculectomy were prospectively evaluated. Eighty eyes of 62 diagnosed with open-angle glaucoma were divided into two the trabeculectomy and XEN Gel Stent groups. Corneal specular microscopy was performed at the central cornea using a noncontact specular microscope preoperatively and 3 months after surgery. RESULTS: The baseline mean corneal endothelial cell density in the trabeculectomy group was 2390.3 ± 324.8 cells/mm2, and this was significantly reduced to 2148 ± 352.5 cells/mm2 3 months after surgery, representing a cell loss of 10.0% (p < 0.001). The baseline mean corneal endothelial cell density in the XEN Gel Stent group was 2156.2 ±559.7 cells/mm2, and this was significantly reduced to 2098.4 ± 556.2 cells/mm2 3 months after surgery, representing a cell loss of 2.1% (p = 0.002). The corneal endothelial cell density change rate of the trabeculectomy group (-10.0% ± 9.7%) was statistically higher than the XEN Gel Stent group (-2.1% ± 13.8%) (p = 0.002). A statistically significant difference was observed in the trabeculectomy group between the baseline and postoperative values in the coefficient of variation (p = 0.029). CONCLUSION: Trabeculectomy caused more endothelial cell damage than XEN Gel Stent implantation in the short-term follow-up period. The XEN Gel Stent may be the treatment of choice in patients with a significantly low preoperative corneal endothelial cell density.

Corneal Endothelial Cell Loss after Baerveldt Glaucoma Implant Surgery.

PURPOSE: To evaluate risk factors for corneal endothelial cell density (ECD) loss after Baerveldt glaucoma implant (BGI) insertion. DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-two patients (72 eyes) with glaucoma. METHODS: Before and 1, 2, 3, 4, and 5 years after anterior chamber BGI insertion, we evaluated the central corneal ECD (CCECD) and peripheral corneal ECD (PCECD) in the area of the tube; anterior chamber (AC) flare; tube insertion entry site position relative to Schwalbe's line (SL), defined as all of the entry site behind SL (tube insertion position 1), less than 50% of entry site anterior to SL (tube insertion position 2), more than 50% but less than 100% of entry site anterior to SL (tube insertion position 3 [TIP3]), and all of the entry site in front of SL (tube insertion position 4 [TIP4]); anterior segment (AS) OCT tube parameters, including posterior cornea-to-tube tip distance, tube angle-to-posterior corneal surface distance, tube tip-to-anterior iris distance, tube length (TL), and tube angle-to-anterior iris distance. MAIN OUTCOME MEASURES: Primary outcomes were CCECD and PCECD loss at 5 years. Secondary outcomes included prognostic factors for ECD loss: tube insertion entry site position relative to SL, AS OCT tube parameters, AC flare, and clinical factors including IOP. RESULTS: Sixty-four patients (64 eyes) completed the study. The mean percentage CCECD and PCECD losses at 5 years were 36.8% and 50.1%, respectively. On univariate analysis at 5 years, a lower CCECD was associated with TIP3. Tube angle-to-anterior iris distance, TL, and TIP3 were associated with lower PCECD at 5 years. Multiple regression analysis revealed TIP3 to be associated with both lower CCECD (standardized ß coefficient, -0.27; P = 0.015) and PCECD (standardized ß coefficient, -0.23; P = 0.028). A short TL (standardized ß coefficient, 0.26; P = 0.016) also was associated with lower PCECD. The fastest rate of cell loss was associated with TIP3 for CCECD and TIP4 for PCECD. CONCLUSIONS: Anterior chamber BGI insertion is associated with ECD loss greatest close to the tube. Tube insertion in the vicinity of, or anterior to SL, and short TL were associated with significant ECD loss with time.