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%.

Five-year clinical outcomes of 107 consecutive DMEK surgeries.

PURPOSE: The long-term clinical outcomes, postoperative complications, and graft survival of Descemet-membrane endothelial keratoplasty (DMEK) remain poorly understood. We retrospectively assessed these variables in all consecutive eyes that underwent DMEK for any indication in 2014-2018. The findings were compared to the long-term DMEK studies of five other groups (3-10-year follow-up). METHODS: Patients underwent ophthalmological tests preoperatively, at 1, 3, 6, and 12 postoperative months, and then annually. Five-year graft survival was determined by Kaplan-Meier estimator. Change in best-corrected visual acuity (BCVA), endothelial-cell density (ECD), and central-corneal thickness (CCT) at each timepoint was determined. RESULTS: 107 eyes (80 patients; 72 years old; 67% female) underwent first-time DMEK for uncomplicated Fuchs endothelial corneal dystrophy (94% of eyes), pseudophakic bullous keratopathy (3%), and regraft after previous keratoplasty (3%). The most common complication was graft detachment requiring rebubbling (18%). Thirteen grafts (12%) failed at ≤15 months. Cumulative 5-year graft-survival probability was 88% (95% confidence intervals = 79-94%). BCVA improved from 0.6 logMAR preoperatively to 0.05 logMAR at 1 year (p<0.0001) and then remained stable. Donor ECD dropped by 47% at 6 postoperative months and then continued to decrease by 4.0%/year. Five-year endothelial-cell loss was 65% (from 2550 to 900 cells/mm2). CCT dropped from 618 to 551 µm at 5 years (p<0.0001). These findings are generally consistent with previous long-term DMEK studies. CONCLUSIONS: DMEK has low complication and high graft-survival rates and excellent clinical outcomes that persist up to 5 years post-surgery. DMEK seems to be a safe and effective treatment in the long term.

Postoperative, but not preoperative, central corneal thickness correlates with the postoperative visual outcomes of Descemet membrane endothelial keratoplasty.

Descemet membrane endothelial keratoplasty (DMEK) restores visual acuity in patients with progressive corneal endothelial diseases such as Fuchs endothelial corneal dystrophy (FECD). However, patients often prefer to delay the surgery as long as possible, even though outcomes are poorer in advanced FECD. A recent study proposed that preoperative central corneal thickness (CCT) of ≥625 µm associated with worse best spectacle-corrected visual acuity (BSCVA) after DMEK for FECD. Since this threshold could signal to both surgeons and patients when to perform DMEK, we further explored the relationship between CCT and BSCVA with a retrospective cohort study. The cohort consisted of all patients with FECD who underwent DMEK in a tertiary-care hospital in 2015-2020 and were followed for 12 months. Extremely decompensated corneas were not included. Relationships between preoperative CCT and BSCVA on days 8 and 15 and months 1, 3, 6, and 12 were examined with Pearson correlation analyses. Eyes with preoperative CCT <625 or ≥625 µm were also compared in terms of postoperative BSCVA. Relationships between postoperative CCT and final BSCVA were also explored. The cohort consisted of 124 first-operated eyes. Preoperative CCT did not correlate with postoperative BSCVA at any timepoint. Eye subgroups did not differ in postoperative BSCVA. However, postoperative CCT at 1-12 months correlated significantly with 12-month BSCVA (r = 0.29-0.49, p = 0.020-0.001). Thus, postoperative, but not preoperative, CCT correlated with postoperative BSCVA. This phenomenon may reflect factors that distort preoperative CCT measurements but disappear after surgery. This observation and our analysis of the literature suggest that while there is a relationship between CCT and post-DMEK visual acuity, preoperative CCT measurements may not always adequately reflect that relationship and may therefore not be a reliable predictor of DMEK visual outcomes.

Membranoproliferative glomerulonephritis after intravitreal vascular growth factor inhibitor injections: A case report and review of the literature.

Systemic administration of agents that inhibit vascular endothelial growth factor (VEGF) and therefore vascular proliferation is often used to treat various cancers. However, these agents are associated with a number of side effects, including proteinuria and renal injury. Intravitreal injection of anti-VEGF agents has become the cornerstone of macular disease treatment. Since these agents cross the blood-retina barrier and enter the circulation, systemic side effects have been reported. We report the novel case of a 57-year-old patient who presented with macular oedema secondary to central retinal vein occlusion, underwent three monthly loading-dose injections with the anti-VEGF agent ranibizumab, and 2 weeks after the second injection presented with biopsy-verified membranoproliferative glomerulonephritis. Twelve weeks after presenting with renal failure and 10 weeks after his last anti-VEGF injection, the patient demonstrated spontaneous recovery of his kidney function. The patient had a history that promoted renal fragility, including hypertension, liver transplantation 6 years earlier for alcohol-related cirrhosis and new-onset diabetes mellitus after transplant. Our literature review and case suggest that although adverse renal events after intravitreal anti-VEGF injections are very rare, ophthalmologists and nephrologists should be aware of this risk.

Evolution of corneal transplantation techniques and their indications in a French corneal transplant unit in 2000-2020.

PURPOSE: This retrospective cohort study assessed the evolution of corneal transplantation and its indications in the last 21 years (2000-2020) in a specialized ophthalmology department in a tertiary referral center in France. METHODS: The surgical techniques and indications, patient age and sex, and postoperative best-corrected visual acuity (BCVA) 6 months after keratoplasty were extracted. RESULTS: In total, 1042 eyes underwent keratoplasty in 2000-2020. Annual numbers of corneal transplantations increased by 2.2-fold. Penetrating keratoplasty (PKP) was the sole technique for the first 11 years. Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) were introduced in 2011 and 2014, respectively. Cases of both quickly increased, accounting for 28% and 41% of cases in 2015-2020, respectively. Eventually, DSAEK and DMEK were respectively used for most pseudophakic bullous keratopathy (PBK) and all Fuchs endothelial cell dystrophy (FECD) cases. PKP cases declined to 27%. Deep anterior lamellar keratoplasty (DALK) was rare (3% of all cases). These changes associated with rises in PBK and particularly FECD cases, and a strong decline in keratoconus, causing FECD, PBK, and keratoconus to move from being the 4th, 1st, and 3rd most common indications to the 1st, 2nd, and 6th, respectively. On average, BCVA improved by 0.1-0.3 logMAR. Patient age dropped steadily over time. Female predominance was observed. CONCLUSIONS: The invention of DSAEK and then DMEK precipitated an enormous change in clinical practice and a large expansion of keratoplasty to new indications. This study confirms and extends previous findings in other countries.

Identification of the preoperative and perioperative factors that predict postoperative endothelial cell density after Descemet membrane endothelial keratoplasty: A retrospective cohort study.

Low postoperative endothelial-cell density (ECD) plays a key role in graft failure after Descemet-membrane endothelial keratoplasty (DMEK). Identifying pre/perioperative factors that predict postoperative ECD could help improve DMEK outcomes. This retrospective study was conducted with consecutive adult patients with Fuchs-endothelial corneal dystrophy who underwent DMEK in 2015-2019 and were followed for 12 months. Patients underwent concomitant cataract surgery (triple-DMEK) or had previously undergone cataract surgery (pseudophakic-DMEK). Multivariate analyses assessed whether: patient age/sex; graft-donor age; preoperative ECD, mean keratometry, or visual acuity; triple DMEK; surgery duration; surgical difficulties; and need for rebubbling predicted 6- or 12-month ECD in the whole cohort or in subgroups with high/low ECD at 6 or 12 months. The subgroups were generated with the clinically relevant threshold of 1000 cells/mm2. Surgeries were defined as difficult if any part was not standard. In total, 103 eyes (95 patients; average age, 71 years; 62% women) were included. Eighteen eyes involved difficult surgery (14 difficult graft preparation or unfolding cases and four others). Regardless of how the study group was defined, the only pre/perioperative variable that associated significantly with 6- and 12-month ECD was difficult surgery (p = 0.01, 0.02, 0.05, and 0.0009). Difficult surgery also associated with longer surgery duration (p = 0.002). Difficult-surgery subgroup analysis showed that difficult graft dissection associated with lower postoperative ECD (p = 0.03). This association may reflect endothelial cell loss due to excessive graft handling and/or an intrinsic unhealthiness of the endothelial cells in the graft that conferred unwanted physical properties onto the graft that complicated its preparation/unfolding.

Graft Thickness at 6 Months Postoperatively Predicts Long-Term Visual Acuity Outcomes of Descemet Stripping Automated Endothelial Keratoplasty for Fuchs Dystrophy and Moderate Phakic Bullous Keratopathy: A Cohort Study.

PURPOSE: It remains unclear whether preoperative central graft thickness (CGT) contributes to visual outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK). This retrospective cohort study examined the ability of preoperative and postoperative CGT to predict 12-month best spectacle-corrected visual acuity (BSCVA) after DSAEK for Fuchs endothelial corneal dystrophy/moderate pseudophakic bullous keratopathy/second graft. METHODS: All consecutive patients who underwent DSAEK in 2015 to 2018 were included. The primary end point was 12-month BSCVA. DSAEK-CGT was measured preoperatively and 6 times between postoperative day 8 and month 12. Eyes were divided according to preoperative CGT 130 µm (ultrathin-DSAEK threshold) or 6-month postoperative CGT 100 µm (mean 6-month postoperative DSAEK-CGT). The t test assessed CGT evolution of the 4 groups over time. Multivariate analyses examined whether preoperative CGT or 6-month CGT categories predicted 12-month BSCVA. Multivariate analysis assessed the preoperative/perioperative factors that predicted 6-month CGT. RESULTS: A total of 108 eyes (68 patients) underwent DSAEK. Preoperative CGT was >130 and ≤130 µm in 87 and 21 eyes, respectively. Postoperative CGT was >100 and ≤100 µm in 50 and 58 eyes, respectively. Thin 6-month postoperative grafts thinned significantly more relative to preoperative thickness than thick grafts ( P < 0.001). Preoperative CGT subgroups did not show this difference. Six-month postoperative CGT ( P = 0.01), but not preoperative CGT, predicted 12-month BSCVA. Preoperative CGT strongly predicted 6-month CGT ( P = 0.0003). CONCLUSIONS: Postoperative, but not preoperative, DSAEK-CGT predicted 6-month BSCVA. The correlation between preoperative and postoperative CGT and interstudy variation in preoperative CGT measurement accuracy may explain literature disparities regarding the importance of preoperative CGT in DSAEK outcomes.

Efficacy and safety of single-step transepithelial photorefractive keratectomy with the all-surface laser ablation SCHWIND platform without mitomycin-C for high myopia: A retrospective study of 69 eyes.

BACKGROUND: Studies suggest that transepithelial photorefractive keratectomy (TransPRK) with the all-surface laser ablation (ASLA)-SCHWIND platform is effective and safe for both low-moderate myopia and high myopia. In most studies, mitomycin-C is administered immediately after surgery to prevent corneal opacification (haze), which is a significant complication of photorefractive keratectomy in general. However, there is evidence that adjuvant mitomycin-C induces endothelial cytotoxicity. Moreover, a recent study showed that omitting adjuvant mitomycin-C did not increase haze in low-moderate myopia. The present case-series study examined the efficacy, safety, and haze rates of eyes with high myopia that underwent ASLA-SCHWIND TransPRK without adjuvant mitomycin-C. METHODS: All consecutive eyes with high myopia (≤-6 D) that were treated in 2018-2020 with the SCHWIND Amaris 500E® TransPRK excimer laser without adjuvant mitomycin-C in a tertiary-care hospital (France) and were followed up for 6 months were identified. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), and spherical equivalent (SE) were recorded before and after surgery. Postoperative haze was graded using the 4-grade Fantes scale. Efficacy rate (frequency of eyes with 6-month UCVA ≤0.1 logMAR), safety rate (frequency of eyes that lost <2 BSCVA lines), predictability (frequency of eyes with 6-month SE equal to target SE±0.5 D), efficacy index (mean UCVA at 6 months/preoperative BSCVA), and safety index (BSCVA at 6 months/preoperative BSCVA) were computed. RESULTS: Sixty-nine eyes (38 patients) were included. Mean preoperative and 6-month SE were -7.44 and -0.05 D, respectively. Mean 6-month UCVA and BSCVA were 0.00 and -0.02 logMAR, respectively. Efficacy rate and index were 95.7% and 1.08, respectively. Safety rate and index were 95.7% and 1.13, respectively. Predictability was 85.5%. Grade 3-4 haze never arose. At 6 months, the haze rate was zero. CONCLUSIONS: ASLA-SCHWIND TransPRK without mitomycin-C appears to be safe as well as effective and accurate for high myopia.