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Purpose: The aim of this study was to assess long-term endothelial cell loss (ECL) and graft failure with Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping endothelial keratoplasty (DSEK) versus penetrating keratoplasty (PK) performed for the same indications (primarily Fuchs dystrophy and pseudophakic corneal edema) in the Cornea Donor Study., Methods: This retrospective study included consecutive primary DMEK (529 recipients, 739 eyes) and DSEK cases (585 recipients, 748 eyes) with 1 or more endothelial cell density (ECD) measurements at 6 months to 16 years. Main outcomes were ECD, longitudinal ECL, and graft failure., Results: Between 6 months and 8 years the ECD declined linearly by approximately 118 cells/mm 2 /yr after DMEK and 112 cells/mm 2 /yr after DSEK. Beyond 8 years postoperatively the rate of decline slowed substantially. Selective dropout from graft failure did not significantly affect the ECD trend. At 10 years, median ECL (interquartile range) was 63% (45, 73) with DMEK, 68% (48, 78) with DSEK, and 76% (70, 82) with PK ( P = 0.01 DMEK vs. DSEK, P <0.001 DMEK vs. PK, and P < 0.001 DSEK vs. PK). The proportion of surviving grafts with 10-year ECD <500 cells/mm 2 was 1.4% with DMEK, 7.3% with DSEK, and 23.9% with PK. The cumulative risk of graft failure between 6 months and 10 years was 5% with DMEK, 11% with DSEK, and 19% with PK ( P < 0.001)., Conclusions: Compared with PK and DSEK, DMEK had significantly lower ECL and significantly lower risk of secondary graft failure through 10 years., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The purpose of this study was to assess off-label use of loteprednol etabonate 0.25% ophthalmic suspension for prevention of immunologic rejection after Descemet membrane endothelial keratoplasty (DMEK)., Methods: This prospective, open-label study enrolled 70 eyes of 70 participants without preexisting glaucoma 1 month after DMEK. Participants used topical loteprednol 0.25% 4 times daily for 2 months, tapered by 1 drop/month to once daily use, and continued use through 1 year after DMEK. Main outcomes were rate of intraocular pressure (IOP) elevation (defined as a relative increase of ≥10 mm Hg over the pretransplant IOP) and rate of initial allograft rejection episodes. The results were compared with historical data using the log-rank test., Results: All participants had Fuchs dystrophy, and 40 of 70 (57%) were female. None (0%) experienced an immunologic graft rejection episode, matching the previously reported efficacy of prednisolone acetate 1% suspension and loteprednol 0.5% gel (both 0% incidence). One study eye developed IOP elevation 3 months after DMEK (cumulative risk 1.5%). Compared with historical data, this was similar to the risk with loteprednol 0.5% gel (4%, P = 0.36) and significantly lower than the risk with prednisolone 1% suspension (18%, P = 0.0025). Two participants (3%) complained of instillation site discomfort, consistent with the 5% rate reported on package labeling., Conclusions: Loteprednol 0.25% suspension, approved for short-term treatment of dry eyes, effectively prevented immunologic rejection episodes with minimal risk of IOP elevation when used from 1 month until 12 months after DMEK in patients without preexisting glaucoma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to compare aqueous humor cytokine levels in eyes with an initial endothelial keratoplasty (EK) that cleared and later decompensated versus control eyes., Methods: In this prospective case-control study, aqueous humor samples were collected under sterile conditions at the start of planned cataract or EK surgery in normal controls (n = 10), Fuchs dystrophy controls with no previous surgery (n = 10) or previous cataract surgery only (n = 10), eyes with Descemet membrane EK (DMEK) endothelial decompensation (n = 5), and eyes with Descemet stripping EK (DSEK) endothelial decompensation (n = 9). Cytokine levels were quantified with the LUNARIS Human 11-Plex Cytokine Kit and compared using the Kruskal-Wallis nonparametric test and post hoc Wilcoxon pairwise 2-sided multiple comparison test., Results: Levels of granulocyte-macrophage colony-stimulating factor, interferon gamma, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, and tumor necrosis factorα did not differ significantly between groups. However, IL-6 was significantly increased in DSEK regraft eyes versus controls without previous ocular surgery. IL-8 was significantly increased in eyes with previous cataract or EK surgery versus eyes without previous surgery, and IL-8 was significantly increased in DSEK regraft eyes versus eyes with previous cataract surgery., Conclusions: The levels of innate immune cytokines IL-6 and IL-8 were elevated in the aqueous humor of eyes with failed DSEK, but not with failed DMEK. The differences between DSEK and DMEK may be related to the lower inherent immunogenicity of DMEK grafts and/or the more advanced stage of some of the DSEK graft failures at the time of diagnosis and treatment., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate spherical intraocular lens (IOL) implantation for cataracts in keratoconic eyes followed by optional refractive toric lens exchange to improve uncorrected visual acuity., Methods: This retrospective study evaluated cataract surgery outcomes in keratoconic eyes. Eyes treated with a spherical IOL targeted for -2.00 diopters (D) either achieved acceptable manifest refraction and desired exchange with a toric IOL (Group 1); achieved satisfactory manifest refraction and chose to use spectacles or contact lenses (Group 2); or did not achieve acceptable refraction and used contact lenses (Group 3). Group 4 had single-stage toric IOL implantation with plano target. Corrected and uncorrected distance visual acuity (CDVA and UDVA) and keratometry were analyzed., Results: Groups 1 to 4 had 18, 23, 18, and 26 eyes, respectively. A staged toric exchange resulted in significantly better ( P = .02) UDVA (mean: 0.15 logMAR; 20/25 Snellen) than initial toric IOL implantation (0.24 logMAR; 20/30 Snellen). All toric IOL exchange eyes achieved 20/30 or better CDVA and 94% had 20/40 or better UDVA. Mean manifest cylinder significantly decreased from 3.39 D before lens exchange to 1.10 D postoperatively., Conclusions: Initial implantation of a spherical IOL in keratoconic eyes allows basing toric calculations on the manifest refraction, which may be more reliable than keratometry measurements in keratoconic eyes. UDVA after staged toric IOL exchange was significantly better than after initial toric IOL implantation. Importantly, by staging use of toric lenses, the authors avoided cases where patients required a rigid contact lens after a toric IOL was implanted. [ J Refract Surg . 2024;40(4):e207-e217.] .

Purpose: The aim of this study was to assess the long-term risk of steroid-induced ocular hypertension and the need for glaucoma treatment with long-term use of topical prednisolone acetate 1% in patients without preexisting glaucoma., Methods: We retrospectively reviewed the charts of 211 patients without previous glaucoma, who underwent Descemet stripping endothelial keratoplasty (DSEK) and used topical prednisolone acetate long-term to prevent graft rejection. Dosing was 4 times daily for 4 months and tapered to once daily. The main outcomes were ocular hypertension (defined as intraocular pressure ≥24 mm Hg, or increase of ≥10 mm Hg over baseline) and initiation of glaucoma treatment., Results: The median patient age was 70 years (range: 34-94 years). The indications for DSEK were Fuchs dystrophy (88%), pseudophakic corneal edema (7%), failed DSEK (3%), and failed penetrating keratoplasty (2%). The median follow-up period was 7 years (range, 1-17 years). At 1, 5, and 10 years, the cumulative risks of steroid-induced ocular hypertension were 29%, 41%, and 49%, respectively, and the risks of requiring glaucoma treatment were 11%, 17%, and 25%, respectively. Among 35 eyes treated for glaucoma, 28 (80%) were managed medically and 7 (20%) had filtration surgery., Conclusions: Long-term use of potent topical corticosteroids, such as prednisolone acetate 1%, entails substantial risk of developing steroid-induced ocular hypertension, so frequent monitoring of intraocular pressure is required. With corneal transplantation, the risk can be mitigated by using techniques with a low inherent risk of rejection, such as Descemet membrane endothelial keratoplasty, whenever possible, to allow earlier reduction of steroid potency., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, age-related, female-predominant disorder characterized by loss of post-mitotic corneal endothelial cells (CEnCs). Ultraviolet-A (UVA) light has been shown to recapitulate the morphological and molecular changes seen in FECD to a greater extent in females than males, by triggering CYP1B1 upregulation in females. Herein, we investigated the mechanism of greater CEnC susceptibility to UVA in females by studying estrogen metabolism in response to UVA in the cornea. Loss of NAD(P)H quinone oxidoreductase 1 (NQO1) resulted in increased production of estrogen metabolites and mitochondrial-DNA adducts, with a higher CEnC loss in Nqo1 -/- female compared to wild-type male and female mice. The CYP1B1 inhibitors, trans-2,3',4,5'-tetramethoxystilbene (TMS) and berberine, rescued CEnC loss. Injection of wild-type male mice with estrogen (E2; 17β-estradiol) increased CEnC loss, followed by increased production of estrogen metabolites and mitochondrial DNA (mtDNA) damage, not seen in E2-treated Cyp1b1 -/- male mice. This study demonstrates that the endo-degenerative phenotype is driven by estrogen metabolite-dependent CEnC loss that is exacerbated in the absence of NQO1; thus, explaining the mechanism accounting for the higher incidence of FECD in females. The mitigation of estrogen-adduct production by CYP1B1 inhibitors could serve as a novel therapeutic strategy for FECD., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to document, to our knowledge, the first reported case of keratoconus progression accompanied with newly diagnosed pellucid marginal degeneration after corneal cross-linking (CXL)., Methods: A novel case of further keratoconus progression plus development of pellucid marginal degeneration in the same eye after CXL was documented with supporting evidence from Scheimpflug and optical coherence tomography imaging., Results: A male patient was diagnosed with progressive keratoconus in the left eye and treated with CXL when aged 25 years. Although strongly cautioned not to rub his eyes, he admitted that he continued eye rubbing in association with atopic disease. At a follow-up examination 3.5 years after CXL, progressive keratoconus was detected and pellucid marginal degeneration was newly diagnosed in the left eye. The eye was retreated with CXL., Conclusions: This case illustrates that progressive keratoconus and pellucid marginal degeneration can occur in the same eye after CXL and demonstrates the deleterious effects that can develop with continued eye rubbing., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Fuchs Endothelial Corneal Dystrophy (FECD), a late-onset oxidative stress disorder, is the most common cause of corneal endothelial degeneration and is genetically associated with CTG repeat expansion in Transcription Factor 4 (TCF4). We previously reported accumulation of nuclear (nDNA) and mitochondrial (mtDNA) damage in FECD. Specifically, mtDNA damage was a prominent finding in development of disease in the ultraviolet-A (UVA) induced FECD mouse model. We hypothesize that an aberrant DNA repair may contribute to the increased DNA damage seen in FECD. We analyzed differential expression profiles of 84 DNA repair genes by real-time PCR arrays using Human DNA Repair RT-Profiler plates using cDNA extracted from Descemet's membrane-corneal endothelium (DM-CE) obtained from FECD patients with expanded (>40) or non-expanded (<40) intronic CTG repeats in TCF4 gene and from age-matched normal donors. Change in mRNA expression of <0.5- or >2.0-fold in FECD relative to normal was set as cutoff for down- or upregulation. Downregulated mitochondrial genes were further validated using the UVA-based mouse model of FECD. FECD specimens exhibited downregulation of 9 genes and upregulation of 8 genes belonging to the four major DNA repair pathways, namely, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and double strand break (DSB) repair, compared to normal donors. MMR gene MSH2 and BER gene POLB were preferentially upregulated in expanded FECD. BER genes LIG3 and NEIL2, DSB repair genes PARP3 and TOP3A, NER gene XPC, and unclassified pathway gene TREX1, were downregulated in both expanded and non-expanded FECD. MtDNA repair genes, Lig3, Neil2, and Top3a, were also downregulated in the UVA-based mouse model of FECD. Our findings identify impaired DNA repair pathways that may play an important role in DNA damage due to oxidative stress as well as genetic predisposition noted in FECD., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to evaluate 15-year outcomes of Descemet stripping endothelial keratoplasty (DSEK)., Methods: We retrospectively reviewed an initial, consecutive series of 350 DSEK cases in 290 patients (mean age 69 years), performed between December 2003 and December 2005 for Fuchs dystrophy (86%), pseudophakic/aphakic bullous keratopathy (10%), or failed penetrating keratoplasty (4%). Outcomes included best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), and graft failure (defined as regraft for any reason or persistent loss of stromal clarity)., Results: At 15 years, 46 of 350 DSEK grafts (13%) had failed, 155 (44%) were in patients who died, and 84 of the remaining 149 grafts (56%) were examined. After accounting for loss to follow-up, the probability of graft failure was 7% at 5 years, 16% at 10 years, and 23% at 15 years. The main risk factor for late endothelial failure was preoperative glaucoma (hazard ratio: 4.4 for medically managed and 24 for surgically managed glaucoma). The probability of an immunologic rejection episode was 7% by 1 year, 14% by 10 years, and 17% by 15 years. The median donor ECD decreased from 3030 cells/mm 2 before DSEK to 1973 cells/mm 2 at 6 months (36% loss) and 705 cells/mm 2 at 15 years (78% loss). The median BSCVA, including the eyes with ocular comorbidity, was 20/60 preoperatively, 20/40 at 3 through 12 months, and 20/30 from 2 to 15 years., Conclusions: DSEK provided excellent long-term visual rehabilitation and graft survival in this early cohort, performed when the technique was still being refined., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate safety and efficacy of a custom-manufactured artificial iris device (CustomFlex Artificial Iris; HumanOptics AG) for the treatment of congenital and acquired iris defects., Design: Multicenter, prospective, unmasked, nonrandomized, interventional clinical trial., Participants: Patients with photophobia, sensitivity secondary to partial or complete congenital or acquired iris defects, or both., Methods: Eyes were implanted from November 26, 2013, to December 1, 2017, with a custom, foldable artificial iris by 1 of 4 different surgical techniques. Patients were evaluated 1 day, 1 week, and 1, 3, 6, and 12 months after surgery. At each examination, slit-lamp findings, intraocular pressure, implant position, subjective visual symptoms, and complications were recorded. Corrected distance visual acuity (CDVA) and endothelial cell density (ECD) were measured at 3, 6, or 12 months as additional safety evaluations. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to assess health-related quality of life affected by vision. The Global Aesthetic Improvement Scale was used to assess cosmetic results., Main Outcome Measures: Photosensitivity, glare, visual symptoms, NEI VFQ-25 score, Global Aesthetic Improvement Scale rating, prosthesis-related adverse events, intraocular lens (IOL)-related adverse events, and surgery-related adverse events 12 months after surgery., Results: At the 12-month postoperative examination, a 59.7% reduction in marked to severe daytime light sensitivity (P < 0.0001), a 41.5% reduction in marked to severe nighttime light sensitivity (P < 0.0001), a 53.1% reduction in marked to severe daytime glare (P < 0.0001), and a 48.5% reduction in severe nighttime glare (P < 0.0001) were found. A 15.4-point improvement (P < 0.0001) in the NEI VFQ-25 total score was found, and 93.8% of patients reported an improvement in cosmesis as measured by the Global Aesthetic Improvement Scale 12 months after surgery. No loss of CDVA of > 2 lines related to the device was found. Median ECD loss was 5.3% at 6 months after surgery and 7.2% at 12 months after surgery., Conclusions: The artificial iris surpassed all key safety end points for adverse events related to the device, IOL, or implant surgery and met all key efficacy end points, including decreased light and glare sensitivity, improved health-related quality of life, and satisfaction with cosmesis. The device is safe and effective for the treatment of symptoms and an unacceptable cosmetic appearance created by congenital or acquired iris defects., (Copyright © 2022. Published by Elsevier Inc.)

Importance: AGN-190584 (Allergan, an AbbVie company) is an optimized topical formulation of pilocarpine hydrochloride, 1.25%, designed for managing presbyopia and enhanced with a proprietary vehicle., Objective: To evaluate the efficacy and safety of pilocarpine hydrochloride, 1.25%, in individuals with presbyopia., Design, Setting, and Participants: This vehicle-controlled, participant- and investigator-masked, randomized, phase 3 clinical study, GEMINI 1, enrolled individuals with presbyopia, aged 40 to 55 years, at 36 sites in the United States from December 21, 2018, to October 31, 2019. Analysis took place between February 2020 and December 2021., Interventions: AGN-190584 or the AGN-190584 formulation vehicle was administered bilaterally, once daily for 30 days., Main Outcomes and Measures: The proportion of participants with improvement of 3 or more lines in mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) at hours 3 and 6 on day 30 were the primary and key secondary efficacy end points, respectively. Safety measures included adverse events., Results: Of 323 participants who were randomized, 235 (72.8%) were female and 292 (90.4%) were White. The mean (SD) age was 49.6 (3.5) years, and the baseline mean (SD) mesopic DCNVA was 29.2 (6.3) letters. A total of 163 individuals were randomized to AGN-190584 and 160 were randomized to vehicle. GEMINI 1 met its primary and key secondary efficacy end points. On day 30, hour 3, the percentage of participants with improvement of 3 or more lines in mesopic DCNVA was 30.7% (50 of 163) in the AGN-190584 group and 8.1% (13 of 160) in the vehicle group (difference, 22.5% [95% CI, 14.3%-30.8%]; adjusted P < .001). At hour 6, those percentages were 18.4% (30 of 163) and 8.8% (14 of 160), respectively (difference, 9.7% [95% CI, 2.3%-17.0%]; adjusted P = .01). At hour 8, the between-group difference in 3 or more lines of mesopic DCNVA gains was not statistically significant, but clinically relevant prespecified outcome measures demonstrated AGN-190584 superiority to vehicle in least-squares mean (SE) mesopic DCNVA change from baseline at hour 8 (5.4 [0.51] vs 3.6 [0.52] letters; P = .009) and photopic distance-corrected intermediate visual acuity at hour 8 (3.9 [0.44] vs 2.4 [0.45] letters; P = .01) and hour 10 (3.5 [0.46] vs 1.7 [0.47] letters; P = .004). No participants with mesopic DCNVA improvement of 3 or more lines at hour 3 had losses of more than 5 letters in mesopic, high-contrast, binocular-corrected distance visual acuity. The onset of effect was at 15 minutes. AGN-190584 demonstrated an acceptable safety and tolerability profile., Conclusions and Relevance: AGN-190584 demonstrated superiority over vehicle in mesopic DCNVA on day 30, hours 3 and 6, with an acceptable safety profile. AGN-190584 is a safe and efficacious topical therapy for presbyopia through 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT03804268.

Purpose: To determine the safety, efficacy, and tolerability of combinations of pilocarpine (Pilo) and oxymetazoline (Oxy) ocular drops dosed once daily and identify the optimal concentration of each for the pharmacologic treatment of presbyopia., Design: Two concurrent Phase 2, multicenter, double-masked, randomized, vehicle-controlled studies, 1 short-term and 1 extended study., Participants: Emmetropic individuals affected by presbyopia and in good general health., Methods: Uncorrected near visual acuity (UNVA) was measured throughout both studies with various concentrations and combinations of Pilo (0%, 0.5% 1.0%, and 1.5%) and Oxy (0%, 0.0125%, 0.05%, and 0.125%). For safety, uncorrected distance visual acuity (UDVA) was measured, treatment-emergent adverse events (TEAEs) were recorded, and a temporal/supraorbital headache assessment was completed., Main Outcome Measures: The primary efficacy end point was mean change from baseline in UNVA., Results: In the short-term study, Pilo was shown to produce a significant dose response in the average increase of letters ( P < 0.001), whereas Oxy did not have a significant impact ( P = 0.4797). The addition or increase in concentration of Oxy did not reduce incidence or severity of headaches when compared with Pilo alone. Efficacy results from the extended study supported the results from the short-term study. As early as 15 minutes postadministration, a dose response could be seen, with peak effect at 1 hour. Peak improvement increased from day 1 to day 14 and was maintained up to day 28. The most common TEAE was headache. There was no clinically significant reduction in UDVA. A polynomial regression model was developed and determined that the optimal concentration range of Pilo is between 1.16% and 1.32%., Conclusions: On the basis of the results of the 2 Phase 2 studies, AGN-190584, a reading drop containing an optimized concentration of pilocarpine HCl (1.25%) delivered using a proprietary formulation, was developed and is currently under investigation in Phase 3 studies., (© 2021 by the American Academy of Ophthalmology.)

Abstract: Studies conducted in the United States suggest that 1% to 2% of corneal donor rims culture positive for fungus; the fungal agent is usually Candida, and the risk of an endothelial keratoplasty recipient developing an intraocular fungal infection is approximately 7% (1 in 15) if the donor rim was culture-positive. Routine culturing of corneal donor rims is useful because a positive fungal culture alerts the surgeon to carefully monitor the keratoplasty recipient for any signs of fungal infection. However, routine implementation of antifungal prophylaxis on receipt of a positive culture is problematic because there is a lack of definitive data regarding the optimal route of administration, necessary duration of prophylaxis, and relative efficacy of different antifungal agents. The use of topical prophylaxis alone has not been proven to be effective, and the systemic agents that are effective against Candida typically involve an azole, which has many side effects, including liver toxicity and potential interactions with other drugs. The data suggest that routine antifungal prophylaxis would needlessly expose 14 patients to systemic side effects for each person who would directly benefit. Treatment of postkeratoplasty fungal infection typically involves graft replacement, but selective removal of the involved area(s) has been used successfully with Descemet membrane endothelial keratoplasty., Competing Interests: The author has no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate off-label use of netarsudil 0.02% for treatment of corneal edema associated with Fuchs dystrophy., Design: Prospective, randomized clinical trial., Methods: Twenty-nine subjects with symptomatic Fuchs dystrophy were enrolled and randomized to use netarsudil or placebo eye drops once daily for 3 months. The primary outcomes were the change in central corneal thickness between baseline and 1 month and between baseline and 3 months. Secondary outcomes included change in scotopic corrected distance visual acuity (CDVA) at 3 months and change in scores on a visual disability questionnaire validated for use with Fuchs dystrophy., Results: Compared with use of placebo, use of netarsudil produced significant reduction in central corneal thickness at 1 month (mean difference, -20 µm; 95% confidence interval, -32 to -9 µm) and 3 months (mean difference, -26 µm; 95% confidence interval, -39 to -12 µm) and significant improvement in scotopic CDVA at 3 months (mean difference +1.6 lines; 95% confidence interval, 0.2-3.0 lines). Scores on the visual disability questionnaire did not change significantly in either arm or differ significantly between arms. One subject assigned to netarsudil had baseline epithelial bullae and withdrew from the study because of disabling glare., Conclusions: Use of netarsudil was associated with reduction of corneal edema and improvement in scotopic CDVA in Fuchs dystrophy patients. Further study is needed to more fully assess patient satisfaction and visual acuity under various lighting conditions and to compare use of netarsudil with other treatment options such as endothelial keratoplasty., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Intraoperative optical coherence tomography (OCT) has the potential to revolutionize lamellar corneal surgery and facilitate many other types of ocular surgery because it readily visualizes ocular structures that can be difficult to discern with a coaxial microscope, particularly through a cloudy cornea. Systems that can provide a high-quality image on demand in the surgeon's oculars, rather than just on an adjacent monitor, are the most useful because they allow the surgeon to rely on the OCT image while operating, without having to look away from the surgical field. Useful applications in lamellar corneal surgery include assessing graft attachment with Descemet stripping endothelial keratoplasty and discerning graft orientation with Descemet membrane endothelial keratoplasty, which otherwise could be challenging in an eye with a cloudy cornea. Intraoperative OCT is particularly helpful when performing deep anterior lamellar keratoplasty in cases in which a big bubble should not be attempted or cannot be achieved because it enables better intraoperative control of the incision depth and allows the surgeon to assess the uniformity of the dissection plane to optimize visual outcomes. Intraoperative OCT is also useful when judging the depth of a scar for a lamellar dissection, when evaluating intraocular lens positioning in the capsular bag, or when locating and removing retained nuclear fragments from an eye with a poor view because of a cloudy cornea. The primary barrier to the adoption of this valuable technology is cost., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Endothelial keratoplasty has revolutionized the treatment of corneal endothelial dysfunction and lowered the threshold for treatment by providing rapid visual rehabilitation and setting a high standard for safety and efficacy. Over time, endothelial keratoplasty techniques have evolved toward the use of thinner tissue to optimize visual outcomes; refinements have facilitated donor tissue preparation, handling, and attachment; and adaptations have expanded utilization in eyes with challenging ocular anatomy. Despite early concerns about graft longevity, emerging 10-year endothelial cell loss and graft survival data have been encouraging. A shortage of human donor corneas restricts utilization in many areas of the world and is driving a search for keratoplasty alternatives. Further work is needed to expand the donor supply, minimize impediments to adoption, optimize graft survival, and improve refractive predictability., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

The cornea is exquisitely designed to protect the eye while transmitting and focusing incoming light. Precise control of corneal hydration by the endothelial cell layer that lines the inner surface of the cornea is required for optimal transparency, and endothelial dysfunction or damage can result in corneal edema and visual impairment. Advances in corneal transplantation now allow selective replacement of dysfunctional corneal endothelium, providing rapid visual rehabilitation. A series of technique improvements have minimized complications and various adaptations allow use even in eyes with complicated anatomy. While selective endothelial keratoplasty sets a very high standard for safety and efficacy, a shortage of donor corneas in many parts of the world restricts access, prompting a search for alternatives. Clinical trials are underway to evaluate the potential for self-recovery after removal of dysfunctional central endothelium in patients with healthy peripheral endothelium. Various approaches to using cultured human corneal endothelial cells are also in clinical trials; these aim to multiply cells from a single donor cornea for use in potentially hundreds of patients. Pre-clinical studies are underway with induced pluripotent stem cells, endothelial stem cell regeneration, gene therapy, anti-sense oligonucleotides, and various biologic/pharmacologic approaches designed to treat, prevent, or retard corneal endothelial dysfunction. The availability of more therapeutic options will hopefully expand access around the world while also allowing treatment to be more precisely tailored to each individual patient., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess whether prophylactic use of netarsudil 0.02% ophthalmic solution reduces the risk of intraocular pressure (IOP) elevation associated with prolonged use of topical corticosteroids to prevent cornea transplantation rejection., Design: Prospective, randomized clinical trial., Methods: In this study, 120 subjects were randomized to use netarsudil (off-label) or placebo once daily for 9 months after Descemet membrane endothelial keratoplasty, and 71 fellow eyes were enrolled and assigned to the opposite treatment arm. Participants concurrently used topical prednisolone acetate 1% 4× daily for 3 months, 3× daily for a month, twice daily for a month, and once daily for 4 months. The main outcome was IOP elevation (defined as IOP ≥24 mm Hg or an increase of ≥10 mm Hg over baseline) assessed by Kaplan-Meier and proportional hazards analyses, taking loss to follow-up into consideration., Results: Overall, 95 eyes were assigned to netarsudil and 96 to placebo; 15 eyes (16%) were withdrawn early from the netarsudil arm because of ocular irritation. The rate of IOP elevation was 14% with netarsudil and 21% with placebo (relative risk: 0.6; 95% confidence interval: 0.3-1.3; P = .23). IOP was >30 mm Hg in 7.8% assigned to netarsudil versus 7.4% assigned to placebo (P = .84). Median 6-month central endothelial cell loss was 31% versus 29% with netarsudil versus placebo, respectively (P = .49)., Conclusions: Netarsudil did not produce a statistically significant reduction in the risk of steroid-induced IOP elevation after corneal transplantation relative to placebo., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To assess outcomes of presbyopia-correcting intraocular lens (IOL) implantation after Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial corneal dystrophy., Methods: This retrospective single-center study evaluated a consecutive series of patients with Fuchs endothelial corneal dystrophy who received presbyopia-correcting IOLs after DMEK. The main outcomes were corrected distance visual acuity, uncorrected distance visual acuity, uncorrected near visual acuity, and refractive error., Results: Fourteen extended depth of focus and 2 bifocal IOLs were implanted in 16 eyes of 8 patients (5 women and 3 men; age, 47-68 years). Fourteen IOLs were spherical and 2 were toric. Postoperatively, the median corrected distance visual acuity was 20/20 (range, 20/15-20/25), the median binocular uncorrected distance visual acuity was 20/25 (range, 20/15-20/25), the median binocular uncorrected near visual acuity was 20/20 (range, 20/20-20/50), and the median manifest spherical equivalent refraction was 0.05 diopters (D) (range, -0.75 to +0.75 D). Implantation of toric extended depth of focus lenses reduced refractive cylinder from 1 and 2.25 D preoperatively to 0 D in both eyes of 1 patient postoperatively. A comparison of biometry measurements taken before and after DMEK showed the median change in average keratometry was 0.26 D with a substantial range of -1.74 to +1.18 D. The median endothelial cell loss was 63 cells/mm (3%) after staged phacoemulsification., Conclusions: Favorable visual and refractive outcomes were obtained with presbyopia-correcting IOLs in patients with Fuchs dystrophy when the biometry measurements and IOL implantation were staged after DMEK had cleared the guttae and corneal edema.

Fuchs Endothelial Corneal Dystrophy (FECD) is an age-related genetically complex disease characterized by increased oxidative DNA damage and progressive degeneration of corneal endothelial cells (HCEnCs). FECD has a greater incidence and advanced phenotype in women, suggesting a possible role of hormones in the sex-driven differences seen in the disease pathogenesis. In this study, catechol estrogen (4-OHE 2 ), the byproduct of estrogen metabolism, induced genotoxic estrogen-DNA adducts formation, macromolecular DNA damage, and apoptotic cell death in HCEnCs; these findings were potentiated by menadione (MN)-mediated reactive oxygen species (ROS). Expression of NQO1, a key enzyme that neutralizes reactive estrogen metabolites, was downregulated in FECD, indicating HCEnC susceptibility to reactive estrogen metabolism in FECD. NQO1 deficiency in vitro exacerbated the estrogen-DNA adduct formation and loss of cell viability, which was rescued by the supplementation of N-acetylcysteine, a ROS scavenger. Notably, overexpression of NQO1 in HCEnCs treated with MN and 4-OHE 2 quenched the ROS formation, thereby reducing the DNA damage and endothelial cell loss. This study signifies a pivotal role for NQO1 in mitigating the macromolecular oxidative DNA damage arising from the interplay between intracellular ROS and impaired endogenous estrogen metabolism in post-mitotic ocular tissue cells. A dysfunctional Nrf2-NQO1 axis in FECD renders HCEnCs susceptible to catechol estrogens and estrogen-DNA adducts formation. This novel study highlights the potential role of NQO1-mediated estrogen metabolite genotoxicity in explaining the higher incidence of FECD in females., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To describe outcomes of customized peripheral anterior lamellar keratoplasty (PALK) for late ectasia of the donor-recipient junction after penetrating keratoplasty (PK) for keratoconus., Methods: This was a single-center, retrospective review of 33 eyes (28 patients) that developed ectasia restricted to the graft-host junction; 17 eyes underwent PALK using lamellar resections of 8- to 11-mm width starting at the external margin of the previous PK and suturing a same-size donor graft (annular or segmental). Five eyes were excluded from analysis because of postoperative complications unrelated to the technique., Results: The average time between PK and diagnosis of secondary ectasia was 28 years (range 9-49 years). Slit-lamp examination showed localized thinning and elongation of the scar at the graft-host junction with well-defined biomicroscopic limits. Preoperatively, the mean keratometric measures were K1: 44.8 ± 4.8 D and K2: 54.1 ± 4.8 D and postoperatively K1: 47.5 ± 3.5 D and K2: 50.8 ± 2.6 D. The mean improvement in corrected visual acuity was 10 lines, and mean cylinder improved from 9.3 ± 2.1 D to 3.3 ± 1.4 D. All cases showed anatomical and refractive improvement., Conclusions: With long-term follow-up, late post-PK ectasia becomes an increasing problem. PALK can be a successful surgical option to reinforce the ectatic area while preserving a functional clear PK. By adding donor corneal tissue, PALK restores the ectatic area, improves visual acuity, keratometric values, and astigmatism, and preserves the functional graft while avoiding the higher risks of a larger diameter PK.

Corneal endothelium (CE) is a monolayer of mitochondria-rich cells, critical for maintaining corneal transparency compatible with clear vision. Fuchs endothelial corneal dystrophy (FECD) is a heterogeneous, genetically complex disorder, where oxidative stress plays a key role in the rosette formation during the degenerative loss of CE. Increased mitochondrial fragmentation along with excessive mitophagy activation has been detected in FECD; however, the mechanism of aberrant mitochondrial dynamics in CE cell loss is poorly understood. Here, the role of oxidative stress in mitophagy activation in FECD is investigated. Immunoblotting of FECD ex vivo specimens revealed an accumulation of PINK1 and phospho-Parkin (Ser65) along with loss of total Parkin and total Drp1. Similarly, modeling of rosette formation with menadione (MN), led to phospho-Parkin accumulation in fragmented mitochondria resulting in mitophagy-induced mitochondrial clearance, albeit possibly in a PINK1-independent manner. Loss of PINK1, phospho-Drp1, and total Drp1 was prominent after MN-induced oxidative stress, but not after mitochondrial depolarization by carbonyl cyanide m-chlorophenyl hydrazone. Moreover, MN-induced mitophagy led to degradation of Parkin along with sequestration of Drp1 and PINK1 that was rescued by mitophagy inhibition. This study shows that in FECD, intracellular oxidative stress induces Parkin-mediated mitochondrial fragmentation where endogenous Drp1 and PINK1 are sequestered and degraded by mitophagy during degenerative loss of post-mitotic cells of ocular tissue., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the outcomes of micropulse transscleral cyclophotocoagulation for intraocular pressure (IOP) control in keratoplasty eyes., Methods: Outcomes of micropulse laser treatments of postkeratoplasty eyes were retrospectively reviewed. IOP was assessed with applanation tonometry. Keratoplasty survival was calculated with Kaplan-Meier survival analysis., Results: Sixty-one eyes in 57 patients received laser treatment; 31 eyes received 1, 21 received 2, 8 received 3, and 1 received 4 treatments. The median follow-up was 21 months (range, 2-35 months). At baseline, the mean IOP was 28 ± 11 mm Hg. At 1, 3, 6, and 12 months after the last treatment, respectively, the numbers of eyes with IOP data were 58, 50, 46, and 38; the mean IOP was 17 ± 7, 17 ± 8, 18 ± 9, and 15 ± 5 mm Hg; the proportions of eyes with IOP ≤ 15 mm Hg were 40%, 51%, 48%, and 55%; and the proportions with IOP ≤ 12 mm Hg were 21%, 29%, 20% and 29%. Six eyes (10%) received subsequent glaucoma filtration surgery. The mean number of antiglaucoma medications used before the initial treatment was 2.7 (range, 0-4) versus 2.2 (range, 0-4) at last follow-up. At baseline, 7 grafts were decompensated and 5 of 54 clear grafts (9%) had endothelial cell density < 700 cells/mm. Graft survival was 94% at 1 year and 81% at 2 years after the initial laser treatment., Conclusions: Micropulse transscleral cyclophotocoagulation is a noninvasive alternative to glaucoma filtration surgery for IOP reduction in keratoplasty eyes.

Purpose: To evaluate outcomes and graft survival of Descemet membrane endothelial keratoplasty (DMEK) for failed penetrating keratoplasty (PK)., Methods: Ninety-three DMEK procedures performed in 84 eyes of 77 patients with failed PK were retrospectively reviewed. The main outcomes were corrected distance visual acuity and graft survival assessed with Kaplan-Meier survival analysis and proportional hazards modeling taking follow-up into consideration., Results: Sixty-nine eyes had 1 previous failed PK, 13 had 2, 1 had 3, and 1 had 4. Ten eyes had failed Descemet stripping endothelial keratoplasty (DSEK) performed under failed PK. Fourteen cases (15%) had previous glaucoma filtration surgery (9 trabeculectomy alone; 5 trabeculectomy and aqueous shunt). Median follow-up was 21 months (range, 1 month to 7 years). Median Snellen corrected distance visual acuity improved from 20/100 preoperatively (range, 20/30 to count fingers) to 20/30 at 6 months postoperatively (n = 73; range, 20/20-20/200). Rebubbling rates were 53% when the diameter of the DMEK graft was oversized, 27% when same sized, and 33% when undersized relative to that of the previous PK graft. Two grafts (2%) experienced an immunologic rejection episode, and 15 (16%) failed, including 5 primary/early failures and 10 late failures. Previous glaucoma surgery was the only significant risk factor for failure (relative risk, 7.1; 95% confidence interval, 2.1-37.0). The 1-, 2-, and 3-year graft survival rates were 96%, 89%, and 89% without versus 78%, 53%, and 39% with previous glaucoma surgery., Conclusions: Treatment of failed PK with DMEK produced similar 4-year survival (76%) and better visual outcomes than previously reported with Descemet stripping endothelial keratoplasty or an initial PK regraft.

Purpose: To improve the detection of corneal ectasia susceptibility using tomographic data., Design: Multicenter case-control study., Methods: Data from patients from 5 different clinics from South America, the United States, and Europe were evaluated. Artificial intelligence (AI) models were generated using Pentacam HR (Oculus, Wetzlar, Germany) parameters to discriminate the preoperative data of 3 groups: stable laser-assisted in situ keratomileusis (LASIK) cases (2980 patients with minimum follow-up of 7 years), ectasia susceptibility (71 eyes of 45 patients that developed post-LASIK ectasia [PLE]), and clinical keratoconus (KC; 182 patients). Model accuracy was independently tested in a different set of stable LASIK cases (298 patients with minimum follow-up of 4 years) and in 188 unoperated patients with very asymmetric ectasia (VAE); these patients presented normal topography (VAE-NT) in 1 eye and clinically diagnosed ectasia in the other (VAE-E). Accuracy was evaluated with ROC curves., Results: The random forest (RF) provided highest accuracy among AI models in this sample with 100% sensitivity for clinical ectasia (KC+VAE-E; cutoff 0.52), being named Pentacam Random Forest Index (PRFI). Considering all cases, the PRFI had an area under the curve (AUC) of 0.992 (94.2% sensitivity, 98.8% specificity; cutoff 0.216), being statistically higher than the Belin/Ambrósio deviation (BAD-D; AUC = 0.960, 87.3% sensitivity, 97.5% specificity; P = .006, DeLong's test). The optimized cutoff of 0.125 provided sensitivity of 85.2% for VAE-NT and 80% for PLE, with 96.6% specificity., Conclusion: The PRFI enhances ectasia diagnosis. Further integrations with corneal biomechanical parameters and with the corneal impact from laser vision correction are needed for assessing ectasia risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To determine whether the reduced risk of immunologic rejection with Descemet membrane endothelial keratoplasty (DMEK) results in a 5-year survival advantage relative to Descemet stripping endothelial keratoplasty (DSEK) and to determine whether matching the donor and recipient sex affects the rejection episode and graft survival rates., Design: Retrospective cohort study., Participants: Patients with Fuchs' endothelial corneal dystrophy treated with DSEK or DMEK., Methods: This study reviewed 2017 consecutive cases (1312 DSEK and 705 DMEK) performed by 13 surgeons between 2003 and 2012 and included the surgeons' first cases. Survival rates were calculated by Kaplan-Meier analysis., Main Outcome Measures: Immunologic rejection episodes, graft failure or replacement for any reason, and endothelial cell loss., Results: The 5-year rejection episode rate was lower with DMEK (2.6% vs. 7.9% with DSEK, relative risk, 0.29; 95% confidence interval, 0.16-0.53) despite early reduction of topical corticosteroids in 25% of the DMEK cases. African Americans (n = 46) had a higher risk of rejection episodes than other races (relative risk, 4.4; 95% confidence interval, 2.0-9.6). The cumulative 5-year survival rate was 93% with DSEK and DMEK (P = 0.86). Forty-four DMEK and 69 DSEK grafts failed or were replaced within 5 years, but only 1 DMEK and 4 DSEK failures followed a rejection episode. Rejection episodes increased endothelial cell loss (P = 0.004) but were not a significant risk factor for graft failure within 5 years (P = 0.90). The mean 5-year endothelial cell loss was similar between DMEK (48%±19%) and DSEK (47%±19%) (P = 0.22). Graft rejection episode and survival rates were not significantly influenced by whether the sex of the donor matched that of the recipient (rejection episodes: P = 0.07 for female recipients and P = 0.33 for male recipients; graft survival: P = 0.67 for female recipients and P = 0.17 for male recipients)., Conclusions: Five-year graft survival was similar between DMEK and DSEK. Although DMEK had a significantly lower risk of immunologic rejection, rejection episodes rarely resulted in graft failure within 5 years with either procedure. Sex matching the donor and recipient provided no survival advantage with DSEK or DMEK., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether graft orientation during insertion affects Descemet membrane endothelial keratoplasty (DMEK) outcomes., Methods: This was a retrospective analysis of 754 consecutive DMEK cases performed by 2 experienced surgeons to treat Fuchs dystrophy. Both surgeons used an intraocular lens insertor. One surgeon always inserted the tissue scrolled endothelium outward (group 1, n = 245). The other surgeon tested 3 methods: endothelium-outward scroll configuration (group 2, n = 161), endothelium-inward trifold configuration (group 3, n = 172), and trifold configuration with concurrent use of an anterior chamber maintainer (group 4, n = 176). The main outcome measures were rebubbling rate, regrafting or failure within 6 months, and 6-month endothelial cell loss. The tissue unfolding time from graft insertion to air fill was measured in a subset of 120 cases by 1 surgeon., Results: The rebubbling rates were comparable across groups (ie, 12%, 10%, 10%, and 13% for groups 1, 2, 3, and 4, respectively, P = 0.21). The 6-month graft failure/replacement rates were comparable across groups (ie, 0.8%, 1.2%, 2.3%, and 0.6%, respectively, P = 0.18). Similarly, the 6-month endothelial cell loss did not differ significantly between groups (ie, 28% ± 11%, 30% ± 13%, 28% ± 15%, and 27% ± 13%, respectively, P = 0.019). In the subset analysis, the tissue unfolding time was similar for scroll and trifold configurations (6.0 ± 3.5 vs. 5.4 ± 3.0 minutes, respectively, P = 0.43)., Conclusions: The outcomes were similar for endothelium-out and endothelium-in (trifold) insertion methods with DMEK, suggesting that the choice is a matter of surgeon preference.

Purpose: To report novel surgical and medical management of intraocular and corneal infection with Candida glabrata that manifested 3 months after Descemet membrane endothelial keratoplasty (DMEK) and to review demographic reasons for increasing fungal contamination of donor tissue., Methods: Demographics, donor rim cultures, diagnostic tests, management, clinical course, outcomes, and donor mate outcomes are reported for a fungal infection after DMEK., Results: The fungal infection was treated for 3 weeks with a combination of intracameral and intracorneal voriconazole and intracameral and topical amphotericin B (off-label use). After initial improvement, the infection appeared to spread to the posterior chamber and the cornea decompensated. Pars plana vitrectomy was performed, and the fungal plaque and underlying area of the graft (approximately 3 mm area) were excised with the vitrector. After surgical intervention, the voriconazole and amphotericin B injections were discontinued, and oral posaconazole was prescribed for 2 months (off-label use). This combination of surgical and medical management successfully cleared the infection. Surprisingly, corneal edema completely resolved, and central DMEK endothelial cell density was 2506 cells/mm 1 month after discontinuing the antifungal injections, which apparently caused reversible endothelial toxicity., Conclusions: The incidence of nosocomial fungal infections, particularly non-albicans Candida, is increasing, as are the rates of positive fungal cultures from corneal donor tissue and postkeratoplasty fungal infections. Prospective studies are needed to assess the value of routine donor cultures, compare the safety and efficacy of various prophylactic treatments, and evaluate addition of antifungals to cold storage media.

Purpose: To evaluate remodeling of the corneal epithelium after epithelium-off corneal cross-linking (CXL)., Methods: In this prospective single-center study, 93 eyes of 93 patients with progressive keratoconus underwent standard CXL. The maximum keratometry was assessed before and after CXL with Scheimpflug imaging, and the epithelial thickness profile across the central 5 mm of the cornea was assessed with spectral-domain optical coherence tomography anterior segment imaging., Results: The mean patient age was 27 ± 11 years; 76 patients (81%) were male and 17 (19%) were female. Between baseline and 6 months after CXL, the mean corneal maximum keratometry flattened from 58.90 to 57.80 diopters (P < .0001). The mean minimum epithelial thickness increased slightly (from 41 ± 6 to 42 ± 7 μm, P = .12), whereas the mean maximum epithelial thickness decreased slightly (from 65 ± 6 to 64 ± 7 μm, P = .067), reducing the net difference between the minimum and maximum epithelial thickness (from 24 ± 9 to 22 ± 9 μm, P = .0023). The difference between the minimum and maximum epithelial thickness was strongly positively correlated with the maximum keratometry reading at baseline (R 2 = 0.38) and at 6 months after CXL (R 2 = 0.59)., Conclusions: Epithelium-off CXL resulted in modest regularization of the epithelial thickness profile across the central 5 mm of the cornea at 6 months. This could slightly mask flattening of the underlying stroma. [J Refract Surg. 2018;34(6):408-412.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To determine whether hypoxia preconditioning can protect corneal endothelial cells from mechanical stress and perioperative procedures mimicking Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: Preconditioning was delivered by 2 hours of 0.5% oxygen incubation in a hypoxia chamber or by exposure to the prolyl hydroxylase inhibitor FG-4592, which prevents hypoxia-inducible factor-1 alpha degradation. Damage to whole corneas was produced by brief sonication. To mimic use with DSAEK, FG-4592-preconditioned and control donor corneas were dissected with a microkeratome, and the posterior donor button was pulled through a transplant insertion device (Busin glide). The area of endothelial damage was determined by trypan blue staining., Results: In all cases, hypoxia preconditioning or incubation with FG-4592 protected corneal endothelial cells from death by mechanical stress. Hypoxia-preconditioned human and rabbit corneas showed 19% and 29% less cell loss, respectively, relative to controls, which were both significant at P < 0.05. FG-4592 preconditioning reduced endothelial cell loss associated with preparation and insertion of DSAEK grafts by 23% relative to the control (P < 0.01)., Conclusions: These results support the hypothesis that preconditioning by hypoxia or exposure to FG-4592 improves corneal endothelial cell survival and may also provide protection during surgical trauma.

Purpose: To investigate whether the riboflavin dosing frequency affects corneal cross-linking efficacy or safety, given that isotonic riboflavin solution is viscous and each installation coats the corneal surface with a film that absorbs some of the incident ultraviolet A light., Design: Prospective, randomized, single-center equivalence trial., Participants: Patients with progressive keratoconus or ectasia after refractive surgery (n = 510)., Methods: One eye per patient was prospectively randomized to 2-minute or 5-minute riboflavin dosing intervals with standard corneal cross-linking (epithelial removal and 30-minute irradiation with 3 mW/cm 2 ultraviolet A light). Block randomization resulted in comparable representation of keratoconus and ectasia after refractive surgery in the 2 treatment arms. Treatment equivalence was assessed using the 2 one-sided test. Fellow eyes (n = 207) were treated with 5-minute dosing and considered in the safety analysis., Main Outcome Measures: The primary hypothesis was equivalent change in the topography-derived maximum keratometry value from baseline to 6 months with 2-minute vs. 5-minute dosing. A ±0.75-diopter margin of equivalence for the treatment difference between dosing regimens was considered clinically relevant. Adverse events and changes from baseline to 6 months in corrected distance visual acuity (CDVA), uncorrected distance visual acuity, and minimum corneal thickness were assessed., Results: The mean reduction in maximum keratometry from baseline was equivalent with 2-minute and 5-minute riboflavin dosing intervals at 6 months (0.97 and 0.76 diopters, respectively; 90% confidence interval for treatment difference, -0.23 to 0.66; per-protocol population). With both dosing intervals, the mean improvement in CDVA was 0.07 logarithm of the minimum angle of resolution or 3.5 letters at 6 months. Of the 635 study and fellow eyes examined at 6 months, 134 (21%) gained and 32 (5%) lost 2 or more lines of CDVA. Three eyes (0.4%) developed sterile infiltrates, 1 (0.1%) had delayed epithelial healing with dendrites, and 3 (0.4%) had recurrent epithelial defects. Three eyes (0.4%) were re-treated., Conclusions: The 2 riboflavin dosing regimens produced equivalent reduction in the maximum keratometry value, with a favorable safety profile., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess patient satisfaction with corneal crosslinking (CXL)., Setting: Price Vision Group, Indianapolis, Indiana, USA., Design: Prospective case series., Methods: Patients treated with the Dresden protocol or accelerated epithelium-off CXL during an 8-year period were invited to participate in an electronic survey., Results: Of the 552 patients who were invited to participate, 448 (80% response rate) completed the electronic survey. The median time from CXL to survey completion was 3.5 years (range 1 to 9 years). The participants were 73% men; 78% had keratoconus, 22% had post-refractive surgical ectasia, and 44% had bilateral treatment. Comparable proportions of those treated with standard and accelerated CXL reported that it halted disease progression (88% versus 87%, respectively, P = .78). A younger treatment age was associated with higher perceived efficacy (P = .0003). The proportion who considered CXL effective was 93% among those with mild keratoconus, 86% with moderate to severe keratoconus, and 78% with post-refractive surgical ectasia (P = .0004). Regarding vision, 41% reported improvement after CXL, 46% noted no change, and 14% perceived continued decline. The mean satisfaction score was 8.8 ± 1.7 (SD) on a scale of 1 (would not recommend CXL) to 10 (definitely would recommend) among those treated for keratoconus and 7.6 ± 2.5 among those treated for ectasia after keratorefractive surgery (P < .0001). Eleven (1.7%) of 644 treated eyes had subsequent keratoplasty., Conclusion: Most patients considered CXL effective. The perceived efficacy did not vary significantly as a function of follow-up time (P = .90), suggesting no discernible fading of effect over the 1- to 9-year follow-up., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify whether intraoperative hyphema from the peripheral iridotomy during Descemet membrane endothelial keratoplasty (DMEK) is associated with anticoagulant or antiplatelet use, age, combined phacoemulsification, or adverse outcomes., Setting: Price Vision Group, Indianapolis, Indiana, USA., Design: Retrospective case series., Methods: Data were obtained from consecutive DMEK cases with an intraoperative iridotomy from July 2015 through July 2016. Hyphema was classified as negative or positive (small or large). Associations with possible risk factors and with transplant outcomes were assessed., Results: Of 445 cases, 262 (59%) were negative for hyphema and 183 (41%) were positive. The proportion of patients who used preoperative anticoagulant or antiplatelet medication did not differ significantly with the hyphema classification (negative hyphema 42%, small hyphema 34%, large hyphema 46%) (P = .31). Likewise, recipient age was not a risk factor for hyphema (P = .085). Hyphema was more likely in cases combined with phacoemulsification than in single DMEK procedures (relative risk, 1.5 [95% confidence interval, 1.2-1.9]). Hyphema was not associated with postoperative rebubbling rates (negative hyphema 10.5%, small hyphema 10.3%, large hyphema 8.0%) (P = .33), 6-month endothelial cell loss (mean = 29%, P = .19), or 6-month visual acuity (mean = 20/25 Snellen in all hyphema groups, P = .98)., Conclusions: Preoperative anticoagulant or antiplatelet use was not a significant risk factor for hyphema. The risk for hyphema was increased somewhat when DMEK was combined with cataract surgery. Intraoperative hyphema did not significantly affect the rebubbling rate, endothelial cell loss, or visual acuity outcomes., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the recurrence of granular corneal dystrophy type 1 (GCD1) after penetrating keratoplasty (PKP), anterior lamellar keratoplasty (ALK), deep anterior lamellar keratoplasty (DALK), and phototherapeutic keratectomy (PTK) in a single population. The time required to achieve best-corrected visual acuity (BCVA) after each intervention was also analyzed., Methods: Retrospective review of all patients with GCD1 from a single center between 1989 and 2016. Surgical interventions were performed 50 times on 28 eyes of 15 patients. Data were primarily analyzed through Cox regression modeling with clustering and robust log-rank testing., Results: Significant recurrence occurred most rapidly after PTK (median time 2.7 years) and was most delayed after PKP (13.7 years). Significant recurrence occurred at a similar interval after ALK and DALK (3.7 and 3.2 years, respectively). Significant recurrence-free survival was longer for PKP than for ALK, DALK, or PTK (P = 0.04). The time required to obtain BCVA was shorter in the PTK group (median 1.8 months) than in the PKP and DALK groups (median 5.3 and 8.4 months, respectively; P = 0.03 and P = 0.02). All groups achieved a similar median BCVA (20/25-20/30)., Conclusions: This series indicates that GCD1 recurrence-free survival is longest after PKP with an associated delay in attaining BCVA. Conversely, PTK provided the fastest visual recovery with shorter recurrence-free survival.

Purpose: To evaluate whether donor and/or recipient diabetes status affects the outcomes of Descemet membrane endothelial keratoplasty (DMEK)., Methods: A consecutive, single-center DMEK case series was reviewed. The outcome measures were success of surgeon tissue preparation, air reinjection rate, Kaplan-Meier 4-year graft replacement/failure rate for any reason, and endothelial cell loss., Results: The donor had a history of diabetes in 504 of 1791 cases (28%) and the recipient in 14%. For donors without and with diabetes, the preparation success rate was 99% versus 95% (P < 0.0001), the air reinjection rate was 16% versus 18% (P = 0.19), and the 4-year graft replacement/failure rate was 7% versus 9%, respectively (P = 0.15). Endothelial cell loss was not associated with donor diabetes (P = 0.76). For recipients without and with diabetes, the 4-year graft replacement/failure rate was 7% versus 9% (P = 0.68), and median endothelial cell loss increased from 27% versus 29% at 1 month to 42% versus 48% at 4 years, respectively (P = 0.02). Recipient use of insulin therapy was associated with poorer graft attachment and a higher air reinjection rate (P = 0.0023)., Conclusions: Although donor diabetes was associated with a 5-fold increased risk of tissue preparation failure, it was not significantly associated with air reinjection, graft survival, or endothelial cell loss. This provides reassurance that tissue prepared successfully from donors with diabetes is safe to use for DMEK. Recipient diabetes was associated with increased endothelial cell loss; the potential effect on longer-term graft survival merits further study.

Endothelial keratoplasty (EK) has revolutionized treatment of corneal endothelial dysfunction. Compared with penetrating keratoplasty (PK), EK provides faster and more reliable visual rehabilitation while maintaining the eye's structural integrity. The number of EK procedures is growing annually and surpassed PK in the United States in 2012. The most widely used iteration, Descemet stripping endothelial keratoplasty (DSEK), implants healthy donor endothelium, Descemet membrane, and posterior stroma. Descemet membrane endothelial keratoplasty (DMEK) eliminates the donor stromal layer. Although more surgically challenging than DSEK, DMEK provides even faster visual rehabilitation and reduced risk of immunologic rejection, so its use is growing. Potential future alternatives to EK that could help address the unmet demand for donor corneas include removing central guttae and regenerating a central endothelial cell layer from healthy peripheral cells in patients with Fuchs' dystrophy or injecting cultured human corneal endothelial cells to rehabilitate eyes without residual healthy endothelium.

Purpose: To assess the rejection episode rate after deep anterior lamellar keratoplasty (DALK) and to identify associated risk factors., Methods: This retrospective review of 251 primary DALK procedures performed by 14 surgeons at a single center between February 2008 and November 2015 evaluated the rejection episode rate and associated risk factors using Kaplan-Meier survival and proportional hazards analyses, which took the length of follow-up into consideration., Results: Transplant indications were keratoconus or ectasia after laser refractive surgery (n = 170, 68%), corneal opacity (n = 72, 28%), and other anterior corneal disease (n = 9, 4%). The median recipient age was 46 years. The overall rejection episode rate was 14% with 18-month median follow-up and a 7-week median postoperative corticosteroid duration. In univariate analysis, increased risk of rejection episodes was associated with younger recipient age [relative risk (RR): 2.1, 95% confidence interval (CI): 1.4-5.2], African American race (RR: 2.1, 95% CI: 1.1-4.1), and use of manual trephination (compared with the femtosecond laser) for the side-cut incisions (RR: 2.7, 95% CI: 1.4-5.2). In multivariate analysis, the combined effect of patient age and race (P = 0.0012) and the side-cut method (P = 0.021) were each significant risk factors., Conclusions: This study demonstrates the substantial rate of rejection episodes that can be induced by corneal stroma in DALK and suggests that postoperative topical corticosteroids should be continued longer than the study's 7-week median and that young African Americans need higher-dose, longer-duration topical corticosteroids. The association between the side-cut method and rejection risk merits further investigation.

Endothelial keratoplasty (EK) has revolutionized corneal transplant surgery by providing rapid visual recovery and improved visual outcomes. In parts of the world with Fuchs endothelial dystrophy, many patients may present with both cataracts and corneal degeneration requiring surgery. Other forms of endothelial decompensation may also present with cataracts. The staging or combination of transplant surgery and cataract surgery depend on both the abilities of the surgeon and the surgical techniques being considered. We currently use phacoemulsification to remove cataracts and routinely perform both cataract surgery and EK with topical anesthesia. The decision to perform either combined or staged cataract and transplant surgery depends upon the examination of the eye including assessment of the anterior chamber depth and the status of the anterior surface of the cornea, which affects the ability to reliably assess keratometry. Additional considerations include the type of lens implant to use, the desired refractive outcome, and the patient's preference about whether to undergo 1 or 2 surgical procedures per eye., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)