Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial.

PURPOSE: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation. DESIGN: Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil. PARTICIPANTS: Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. METHODS: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks. MAIN OUTCOME MEASURE: The 52-week endothelial immune rejection rate. RESULTS: Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis. CONCLUSIONS: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.

Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media.

PURPOSE: To evaluate the cost-effectiveness of supplementing hypothermic cold storage media (CSM) with antifungal therapy. DESIGN: Cost-effectiveness analysis (CEA). PARTICIPANT: Base case of a patient with Fuch's endothelial dystrophy undergoing a first eye keratoplasty. METHODS: Cost-effective analysis of the base case with corneal tissue stored in CSM or CSM supplemented with antifungal therapy over a 16-year time horizon. Multiple clinical scenarios were considered, including endothelial keratoplasty (EK) and penetrating keratoplasty (PK); amphotericin B, voriconazole, caspofungin, and combination therapy; and third-party payer and societal perspectives. The incidences were derived from PubMed literature searches and average wholesale prices of medications; all costs were discounted 3% per annum and adjusted for inflation to 2019 US dollars. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs). RESULTS: In the reference case, a corneal endothelial graft stored in amphotericin B-supplemented CSM was the most cost-effective approach from a third-party payer and societal perspective. Probability sensitivity analysis (PSA) of the societal model for the EK was robust, with 93.5% being below an arbitrary willingness-to-pay threshold (WTP) of $20 000 per fungal infection averted. Voriconazole, caspofungin, and combination antifungals were less cost-effective than amphotericin B. The main factors influencing the CEA were the incidences of postkeratoplasty fungal infections, potential increases in graft failures, and antifungal costs. For grafts intended for PKs, antifungal supplementation was less cost-effective than for EKs. CONCLUSIONS: Antifungal supplementation with amphotericin B for EK grafts was the most cost-effective approach of the studied antifungals; however, the CEA was sensitive to potential changes in graft failure rates, underlining the importance of long-term safety studies. For full-thickness corneal grafts, antifungal supplementation was less cost-effective.

Diagnostic Performance of 3-Dimensional Thickness of the Endothelium-Descemet Complex in Fuchs' Endothelial Cell Corneal Dystrophy.

PURPOSE: To describe the diagnostic accuracy of 3-dimensional (3D) endothelium-Descemet's membrane complex thickness (En-DMT) in Fuchs' endothelial corneal dystrophy (FECD) and determine its potential role as an objective index of disease severity. DESIGN: Observational case-control study. PARTICIPANTS: One hundred four eyes of 79 participants (64 eyes of 41 FECD patients and 40 eyes of 38 healthy controls). METHODS: All participants received high-definition OCT imaging (Envisu R2210; Bioptigen, Buffalo Grove, IL). Fuchs' endothelial corneal dystrophy was classified clinically into early-stage (without edema) and late-stage (with edema) disease. Automatic and manual segmentation of corneal layers was performed using a custom-built segmental tomography algorithm to generate 3D maps of total corneal thickness (TCT) and En-DMT of the central 6-mm cornea. Regional En-DMT, regional TCT, and central-to-peripheral total corneal thickness ratio (CPTR) were evaluated and correlated to the clinical severity of FECD. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess the reliability of the repeated measurements in all eyes. MAIN OUTCOME MEASURES: Central-to-peripheral total corneal thickness ratio and average En-DMT and TCT of central, paracentral, and peripheral regions. RESULTS: In FECD, a significant increase in En-DMT, CPTR, and TCT was found compared to controls (P < 0.001). For identifying FECD, average En-DMT of paracentral and peripheral regions achieved 94% sensitivity and 100% specificity (cutoffs, 19 µm and 20 µm, respectively), whereas CPTR showed 94% sensitivity with a 73% specificity (cutoff, 0.97). Regarding early-stage FECD, average En-DMT of central zones achieved 92% sensitivity and 97% specificity (cutoff, 18 µm), whereas CPTR showed 90% sensitivity and 88% specificity (cutoff, 0.97). The average En-DMT of central, paracentral, and peripheral regions was correlated highly with FECD clinical stage (Spearman's ρ = 0.813, 0.793, and 0.721, respectively; all P < 0.001), compared with CPTR and mean TCT of paracentral zones (0.672 and 0.481, respectively; P < 0.001). The ICC values ranged from 0.98 (En-DMT) to 0.99 (TCT) with a good agreement between the automatic and manual measurements. CONCLUSIONS: Regional 3D En-DMT is a novel diagnostic tool of FECD that can be used to quantify the disease severity with excellent reliability.

Cost-Effectiveness Analysis of Descemet's Membrane Endothelial Keratoplasty Versus Descemet's Stripping Endothelial Keratoplasty in the United States.

PURPOSE: To determine the cost-effectiveness of Descemet's membrane endothelial keratoplasty (DMEK) compared with Descemet's stripping automated endothelial keratoplasty (DSAEK) in the United States. DESIGN: Cost-effectiveness analysis in a surgical center in the United States. PARTICIPANTS: Binocular adult patient undergoing endothelial keratoplasty. METHODS: A base case of a 70-year-old man undergoing his first endothelial keratoplasty for bilateral Fuchs endothelial dystrophy. The cost-effectiveness of DMEK was compared with DSAEK over a 15-year time horizon. The incidences and costs of complications were derived from PubMed English literature searches, Medicare reimbursements, and average wholesale prices. All costs were discounted 3% per annum and adjusted for inflation to 2018 U.S. dollars. Uncertainty was evaluated using deterministic and probabilistic sensitivity analyses. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios and incremental cost-utility ratios, measured in cost per quality-adjusted life-years (QALYs). RESULTS: Performing a DMEK instead of a DSAEK generated an extra 0.4 QALYs over a 15-year period. From a societal and third-party payer perspective, DMEK was cost-saving when compared with DSAEK in improving visual acuity in the base case. Probabilistic sensitivity analyses with variations in the costs and rebubble rates revealed that DMEK was cost-saving compared with DSAEK in 38% of iterations and was within a societal willingness-to-pay threshold of $50 000 in 98% of models. CONCLUSIONS: From the societal and third-party payer perspectives in the United States, DMEK generated greater utilities and was less costly than DSAEK. Therefore, DMEK was the dominant procedure and was cost-saving with respect to DSAEK. The economic model was robust based on sensitivity analyses.

Donor, Recipient, and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study.

PURPOSE: To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter, double-masked, randomized clinical trial. PARTICIPANTS: One thousand ninety individuals (1330 study eyes) with a median age of 70 years undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE; 6% of eyes). METHODS: Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (n = 675) or 8 to 14 days (n = 655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as regraft for any reason, a graft that failed to clear by 8 weeks after surgery, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was classified further as primary donor failure or early failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and 99% confidence intervals (CIs) for graft failure. MAIN OUTCOME MEASURES: Graft success at 3 years. RESULTS: One thousand two hundred fifty-one of 1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with increased risk for primary or early failure. Preoperative diagnosis of PACE (RR, 3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by 3 years after surgery compared with Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR, 1.19 per decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft insertion (RR, 0.92; 99% CI, 0.40-2.10). CONCLUSIONS: Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study.

Wavelike Interface Opacities After Descemet-Stripping Automated Endothelial Keratoplasty: 7-Year Follow-up.

PURPOSE: To report a case of wavelike interface opacities in a patient who underwent Descemet-stripping automated endothelial keratoplasty (DSAEK) and was managed conservatively over the course of 7 years. METHODS: A 65-year-old woman underwent DSAEK for pseudophakic bullous keratopathy. Textural wavelike opacities were noted in the graft-host interface 6 days postoperatively without evidence of anterior segment inflammation. The patient's vision was also initially limited by the presence of cystoid macular edema (CME). Six months postoperatively, CME had resolved but the patient's vision failed to improve better than 20/80 because of the persistent dense interface opacities. The patient refused to undergo graft exchange despite a suboptimal visual result and she therefore was observed over time. RESULTS: The interface opacities started to regress and her visual acuity improved to 20/30 by 9 months postoperatively. The opacities became gradually less prominent over the next few years, and at 7 years postoperatively, her best-corrected vision was 20/25. CONCLUSION: In this case, observation of this post-DSAEK complication rather than surgical intervention resulted in a favorable long-term visual outcome.

Corneal elasticity after oxygen enriched high intensity corneal cross linking assessed using atomic force microscopy.

The purpose of this study was to assess anterior and mid corneal stromal elasticity after high intensity (HI) corneal cross linking (CXL), with and without oxygen (O2) enrichment, and compare these results to conventional CXL. Experiments were performed on 25 pairs of human cadaver eyes, divided into four different groups. Group 1 included corneas that did not receive treatment and served as controls; Group 2 included corneas that received conventional CXL treatment (Dresden Protocol: corneal epithelial debridement, 30 min of riboflavin pretreatment followed by 30 min of exposure to 3 mW/cm2 of ultraviolet light); Group 3 included corneas that received HI CXL treatment (corneal epithelial debridement, 30 min of riboflavin pretreatment followed by 3 min of exposure to 30mW/cm2 of ultraviolet light); and Group 4 included corneas that received the same treatment as Group 3, except that they were enriched with oxygen (4 L per minute pure O2 gas stream) during ultraviolet irradiation. In each group, corneas were subdivided to assess anterior stromal elasticity and mid stromal elasticity. Corneal stromal elasticity was quantified using Atomic Force Microscopy (AFM) through micro-indentation. Young's modulus for the anterior corneal stroma was 14.5 ± 6.0 kPa, 80.7 ± 44.6 kPa, 36.6 ± 10.5 kPa, and 30.6 ± 9.2 kPa, for groups 1, 2, 3 and 4 respectively. Young's modulus for the mid corneal stroma was 5.8 ± 2.0 kPa, 20.7 ± 4.3 kPa, 12.1 ± 4.9 kPa, and 11.7 ± 3.7 kPa, for groups 1, 2, 3 and 4, respectively. In the anterior stromal region, conventional CXL demonstrated a significantly different result from the control, whereas the two HI CXL protocols were not significantly different from the control. There were no statistical differences between the two HI CXL protocols, although only the HI CXL protocol with O2 enrichment was significantly different from the conventional CXL group. In the mid stromal region, once again only conventional CXL demonstrated a significantly different result from the control. There were no statistical differences between the two HI CXL protocols, and both HI CXL protocols were significantly different from the conventional CXL group. Oxygen enriched HI CXL seems to offer similar changes in corneal elasticity when compared to HI CXL without the presence O2. Conventional CXL increases corneal stiffness more than HI CXL both with and without O2 enrichment.

Corneal stromal elasticity and viscoelasticity assessed by atomic force microscopy after different cross linking protocols.

The purpose of this study was to evaluate elasticity and viscoelasticity in the anterior and deeper stromal regions of the cornea after cross linking with three different protocols using atomic force microscopy (AFM) through indentation. A total of 40 porcine corneas were used in this study and were divided into 4 groups (10 corneas per group): control (no treatment), Dresden (corneal epithelial debridement, riboflavin pretreatment for 30 min and a 3mw/cm(2) for 30 min UVA irradiation), accelerated (corneal epithelial debridement, riboflavin pretreatment for 30 min and a 30mw/cm(2) for 3 min UVA irradiation), and genipin (corneal epithelial debridement and submersion of anterior surface in a 1% genipin solution for 4 h). Elasticity and viscoelasticity were quantified using AFM through indentation for all corneas, for the anterior stroma and at a depth of 200 µm. For the control, Dresden, accelerated, and genipin groups, respectively, the average Young's modulus for the anterior stromal region was 0.60 ± 0.58 MPa, 1.58 ± 1.04 MPa, 0.86 ± 0.46 MPa, and 1.71 ± 0.51 MPa; the average for the 200 µm stromal depth was 0.08 ± 0.06 MPa, 0.08 ± 0.04 MPa, 0.08 ± 0.04 MPa, and 0.06 ± 0.01 MPa. Corneas crosslinked with the Dresden protocol and genipin were significantly stiffer than controls (p < 0.05) in the anterior region only. For the control, Dresden, Accelerated, and genipin groups, respectively, the average calculated apparent viscosity for the anterior stroma was 88.2 ± 43.7 kPa-s, 8.3 ± 7.1 kPa-s, 8.1 ± 2.3 kPa-s, and 9.5 ± 3.8 kPa-s; the average for the 200 µm stromal depth was 35.0 ± 3.7 kPa-s, 49.6 ± 35.1 kPa-s, 42.4 ± 17.6 kPa-s, and 41.8 ± 37.6 kPa-s. All crosslinking protocols resulted in a decrease in viscosity in the anterior region only (p < 0.05). The effects of cross-linking seem to be limited to the anterior corneal stroma and do not extend to the deeper stromal region. Additionally, the Dresden and genipin protocols seem to produce a stiffer anterior corneal stroma when compared to the accelerated protocol.

Intrastromal Corneal Ring Segment Explantation in Patients With Keratoconus: Causes, Technique, and Outcomes.

PURPOSE: To assess the causes for intrastromal corneal ring segment (Intacs; Addition Technology Inc., Lombard, IL) explantation in patients with keratoconus, and technique for explantation, long-term outcomes, and secondary procedures to correct visual acuity. METHODS: Ten eyes of 8 patients with a history of Intacs explantation between 2004 and 2012 were included in a retrospective study performed at the Bascom Palmer Eye Institute, Miami, Florida. Causes of Intacs removal, surgical technique, preoperative and postoperative corneal examination, and uncorrected and corrected distance visual acuity were documented. Additionally, corneal topography (Tomey, Nagoya, Japan) parameters such as average keratometry and corneal cylinder were assessed. RESULTS: Although the segments were well positioned, the most common cause of Intacs removal was worsening visual acuity (80%). There was no statistically significant difference between pre-Intacs placement, post-Intacs placement, and post-Intacs removal in uncorrected and corrected distance visual acuity, average keratometry, or corneal cylinder, except between 1-year post-Intacs placement corrected distance visual acuity (0.57 logMAR [20/75 Snellen]) and 1-month post-Intacs removal corrected distance visual acuity (0.25 logMAR [20/36 Snellen], P =.03). Four patients underwent penetrating keratoplasty after Intacs removal with good visual outcomes. CONCLUSION: This study demonstrates the visual and structural outcomes that returned to near baseline after Intacs explantation in keratoconic eyes.

Application of a hydrogel ocular sealant to avoid recurrence of epithelial ingrowth after LASIK enhancement.

PURPOSE: To report a case of clinically significant epithelial ingrowth after LASIK that was successfully treated with a hydrogel ocular sealant in combination with flap lifting and scraping technique. METHODS: Case report. RESULTS: A 56-year-old woman underwent LASIK and a LASIK enhancement procedure in 2002 and 2012, respectively. Six months after the enhancement, visually significant epithelial ingrowth developed in both of her eyes. The left eye was treated with flap lifting, scraping, and suturing, and the right eye was treated with a hydrogel ocular sealant in combination with flap lifting and scraping. No recurrence was evident during a 6-month follow-up period and visual acuity improved in both eyes. No adverse effects were noticed. CONCLUSIONS: Recurrent epithelial ingrowth may be successfully avoided with the intraoperative use of a hydrogel ocular sealant combined with flap lifting and scraping. This approach could be used as an alternative to LASIK flap suturing.

Intraoperative refractive biometry for predicting intraocular lens power calculation after prior myopic refractive surgery.

PURPOSE: To evaluate a new method of intraoperative refractive biometry (IRB) for intraocular lens (IOL) power calculation in eyes undergoing cataract surgery after prior myopic LASIK or photorefractive keratectomy. DESIGN: Retrospective consecutive cases series. PARTICIPANTS: We included 215 patients undergoing cataract surgery with a history of myopic LASIK or photorefractive keratectomy. METHODS: Patients underwent IRB for IOL power estimation. The Optiwave Refractive Analysis (ORA) System wavefront aberrometer was used to obtain aphakic refractive measurements intraoperatively and then calculate the IOL power with a modified vergence formula obtained before refractive surgery. Comparative effectiveness analysis was done for IRB predictive accuracy of IOL power determination against 3 conventional clinical practice methods: surgeon best preoperative choice (determined by the surgeon using all available clinical data), the Haigis L, and the Shammas IOL formulas. MAIN OUTCOME MEASURES: Median absolute error of prediction and percentage of eyes within ±0.50 diopters (D) and ±1.00 D of refractive prediction error. RESULTS: In 246 eyes (215 first eyes and 31 second eyes) IRB using ORA achieved the greatest predictive accuracy (P < 0.0001), with a median absolute error of 0.35 D and mean absolute error of 0.42 D. Sixty-seven percent of eyes were within ±0.5 D and 94% were within ±1.0 D of the IRB's predicted outcome. This was significantly more accurate than the other preoperative methods: Median absolute error was 0.6, 0.53, and 0.51 D for surgeon best choice, Haigis L method, and Shammas method, respectively. CONCLUSIONS: The IOL power estimation in challenging eyes with prior LASIK/photorefractive keratectomy was most accurately predicted by IRB/ORA.

The use of Bowman's layer vertical topographic thickness map in the diagnosis of keratoconus.

PURPOSE: To evaluate the use of Bowman's layer (BL) vertical topographic thickness maps in diagnosing keratoconus (KC). DESIGN: Prospective, case control, interventional case series. PARTICIPANTS: A total of 42 eyes: 22 eyes of 15 normal subjects and 20 eyes of 15 patients with KC. INTERVENTION: Bowman's layer 2-dimensional 9-mm vertical topographic thickness maps were created using custom-made ultra high-resolution optical coherence tomography. MAIN OUTCOME MEASURES: Bowman's layer average and minimum thicknesses of the inferior half of the cornea, Bowman's ectasia index (BEI; defined as BL minimum thickness of the inferior half of the cornea divided by BL average thickness of the superior half of the cornea multiplied by 100), BEI-Max (defined as BL minimum thickness of the inferior half of the cornea divided by BL maximum thickness of the superior half of the cornea multiplied by 100), keratometric astigmatism (Ast-K) of patients with KC, and average keratometric (Avg-K) readings. RESULTS: In patients with KC, BL vertical thickness maps disclosed localized relative inferior thinning of the BL. Inferior BL average thickness (normal = 15±2, KC = 12±3 µm), inferior BL minimum thickness (normal = 13±2, KC = 7±3 µm), BEI (normal = 91±7, KC = 48±14), and BEI-Max (normal = 75±8; KC = 40±13) all showed highly significant differences in KC compared with normal subjects (P< 0.001). Receiver operating characteristic (ROC) curve analysis showed excellent predictive accuracy for BEI and BEI-Max with 100% sensitivity and specificity (area under the curve [AUC] of 1) with cutoff values of 80 and 60, respectively. The AUC of inferior BL average thickness and minimum thickness were 0.87 and 0.96 with a sensitivity of 80% and 93%, respectively, and a specificity of 93% and 93%, respectively. Inferior BL average thickness, inferior BL minimum thickness, BEI, and BEI-Max correlated highly to Ast-K (R = -0.72, -0.82, -0.84, and -0.82, respectively; P< 0.001) and to Avg-K (R = -0.62, P< 0.001; R = -0.59, P = 0.001; R = -0.60, P< 0.001; and R = -0.59, P = 0.001, respectively). CONCLUSIONS: Bowman's layer vertical topographic thickness maps of patients with KC disclose characteristic localized relative inferior thinning. Inferior BL average thickness, inferior BL minimum thickness, BEI, and BEI-Max are qualitative and quantitative indices for the diagnosis of KC that accurately correlate with the severity of KC. In our pilot study, BEI and BEI-Max showed excellent accuracy, sensitivity, and specificity in the diagnosis of KC.

Femtosecond laser-assisted astigmatic keratotomy for postoperative trabeculectomy-induced corneal astigmatism.

PURPOSE: To describe a case of postoperative trabeculectomy-induced corneal astigmatism treated with femtosecond laser-assisted astigmatic keratotomy. METHODS: After trabeculectomy, the patient demonstrated change in manifest refraction from -0.5 diopters preoperatively to mixed astigmatism of -3.5 + 5.25@100 postoperatively and a decrease in uncorrected distance visual acuity from 20/60 preoperatively to 20/200 at 1 month postoperatively. Because the patient was intolerant to spectacle use, she underwent femtosecond laser-assisted astigmatic keratotomy. RESULTS: After astigmatic keratotomy there was improvement in corneal topographic astigmatism from 4.15 to 0.81 diopters with uncorrected distance visual acuity of 20/60(-2) and manifest refraction of -0.75 + 1.0@90 at 3 months postoperatively. There were no intraoperative or postoperative complications. CONCLUSIONS: Femtosecond laser-assisted astigmatic keratotomy may be considered in eyes with postoperative trabeculectomy-induced mixed astigmatism.

Refractive and topographic fluctuations due to intracorneal ring segments motility.

PURPOSE: To describe a patient with refractive and topographic fluctuations 5 years after intracorneal ring segments (ICRS) implantation for the management of corneal ectasia after LASIK. METHODS: Case report. RESULTS: A 48-year-old woman presented complaining of intermittent decreased vision over 1 year that improved with eye rubbing. Slit-lamp and optical coherence tomography (OCT) examinations revealed overriding ring segments that could be restored to normal position after minor corneal massage. Topographic and refractive findings were significantly influenced by the ICRS positioning and caused decreased visual function when overriding. To avoid ICRS override, surgical dissection of the corneal tunnel along with ring segment repositioning was performed. A suture was placed through the ring's positioning hole to stabilize the ICRS at its optimal position and to avoid recurrence of this phenomenon. CONCLUSIONS: Patients undergoing femtosecond laser-assisted ICRS implantation may experience ring segment migration and override of the segments that could lead to decreased visual function. Proper surgical repositioning and ring segment fixation may address this complication and offer satisfactory visual and refractive outcomes along with avoidance of ICRS migration and override.

Surface quality of human corneal lenticules after SMILE assessed using environmental scanning electron microscopy.

PURPOSE: To assess the cut quality of the anterior and posterior surfaces of intrastromal refractive lenticules removed during small incision lenticule extraction (SMILE). METHODS: The VisuMax femtosecond laser (500 kHz; Carl Zeiss Meditec, Dublin, CA) was used to perform SMILE on 8 eyes of 5 individuals to correct only myopia (no cylinder). The cut energy index was 26 (equivalent to an energy of 130 nJ) with a 2.5 × 2.5 µm spot/track separation. The lenticule diameter was 6.5 mm with a minimum edge thickness of 15 µm and the cap diameter was 7.3 mm with an intended thickness of 120 µm. After laser treatment, the lenticule was loosened with a spatula and removed with forceps. The extracted lenticules were placed in 2% formalin and sent for imaging with an environmental scanning electron microscope. Images of the anterior and posterior surfaces of the lenticules were obtained at multiple magnifications (100×, 250×, and 500×). Surface quality was evaluated by an investigator who specializes in electron microscopy using three criteria: overall surface regularity, percent of surface irregularity, and position of irregular area. RESULTS: Both the anterior and posterior surfaces of the extracted lenticules were smooth and absent of surface irregularities. The cut edges also appeared uniform. Jagged edges were seen in several images, but were clearly caused by the forceps during extraction. CONCLUSIONS: Using the VisuMax laser to perform SMILE produces smooth cuts absent of surface irregularities.

Ocular Dirofilariasis: A Clinicopathologic Case Series and Literature Review.

Purpose: Ocular dirofilariasis is an uncommon zoonotic infection that is usually associated with a carnivore host. In this case series and literature review, we investigate the clinical presentation, management, and histopathology of ocular dirofilariasis. Methods: The database at the Florida Lions Ocular Pathology Laboratory was searched for surgical specimens at the Bascom Palmer Eye Institute under approval of the Institutional Review Board. Patients with a histopathologic diagnosis of dirofilariasis between the years 1962 and 2022 from the Florida Lions Ocular Pathology Laboratory database were included (n = 3). A systematic PubMed search was conducted by two independent authors to identify published cases of ophthalmic dirofilariasis worldwide. Keywords were used to identify articles, and exclusion criteria were applied. Results: Three patients, two males and one female, were identified from the Florida Lions Ocular Pathology Laboratory database with a diagnosis of ocular dirofilariasis. The mean age was 46.7 years (with a range 33-57 years). There were two eyelid lesions (Cases 1 and 3) and one involving the subconjunctival space (Case 2). All three organisms were excised and presumptively identified as Dirofilaria tenuis. All 3 patients were managed with curative surgical removal and recovered completely. Our review of the literature identified 540 published reports and 142 published reports with 186 cases that met the exclusion criteria. Conclusion: We present a case series and literature review of ocular dirofilariasis. Knowledge of the incidence, risk factors, prevention, and diagnosis of this unique parasitic infection will help in proper management and prevent further ocular complications.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation.

Purpose: To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Design: Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. Participants: The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Methods: Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Main Outcome Measures: Vessel and invasion area of vessels in the corneal graft and host beds. Results: This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P = 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P = 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. Conclusions: In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Anterior and posterior corneal stroma elasticity after corneal collagen crosslinking treatment.

The purpose of this project was to assess anterior and posterior corneal stromal elasticity after corneal collagen cross linking (CXL) treatment in human cadaver eyes using Atomic Force Microscopy (AFM) through indentation. Twenty four human cadaver eyes (12 pairs) were included in this study and divided into 2 groups (6 pairs per group). In both groups, the left eye (OS) served as a control (no riboflavin or CXL treatment was performed) and the right eye (OD) underwent CXL treatment (30 min of riboflavin pretreatment followed by 30 min of exposure to 3 mW/cm(2) of ultraviolet light). In group 1, the anterior stroma was exposed by manual delamination of approximately 50 µm of the corneal stroma including Bowman's membrane. In group 2, the posterior stroma was exposed by delamination of the anterior 50% of the corneal stroma including Bowman's membrane. Delamination was performed after crosslinking treatment in the case of the treated eyes. In all eyes, the stromal elasticity was quantified using AFM through indentation. Young's modulus of elasticity for the anterior cornea (group 1) was 245.9 ± 209.1 kPa (range: 82.3-530.8 kPa) for the untreated control eyes, and 467.8 ± 373.2 kPa (range: 157.4-1126 kPa) for the CXL treated eyes. Young's modulus for the posterior cornea (group 2) was 100.2 ± 61.9 kPa (range: 28.1-162.6 kPa) for the untreated control eyes and 66.0 ± 31.8 kPa (range: 31.3-101.7 kPa) for the CXL treated eyes. Young's modulus of the anterior stroma significantly increased after CXL treatment (p = 0.024), whereas the posterior stroma did not demonstrate a significant difference in Young's modulus after CXL treatment (p = 0.170). The anterior stroma was stiffer than the posterior stroma for both the control and CXL treatment groups (p = 0.077 and p = 0.023, respectively). Our findings demonstrate that stiffness of the anterior corneal stroma after CXL treatment seems to increase significantly, while the posterior stroma does not seem to be affected by CXL.

Agreement between Pentacam and IOL master in patients undergoing toric IOL implantation.

PURPOSE: To investigate inter-device agreement between the Pentacam (Optikgerate GmbH, Wetzlar, Germany) and IOLMaster (Carl Zeiss Meditec, Jena, Germany) in measuring corneal power, cylinder, and axis of astigmatism. METHODS: Retrospective case series reviewing the status of eyes after toric IOL implantation to evaluate inter-device agreement in measuring corneal power, cylinder, and axis of astigmatism. RESULTS: Forty-nine eyes from 41 patients were evaluated. Agreement for corneal power and cylinder were deemed good and moderate, with 95% limits of agreement of -1.02 to +1.13 and -1.37 to +1.09 diopters (D), respectively. Agreement for axis of astigmatism was only fair, with a mean absolute difference of 8.9 degrees (range: 0.3 to 37.7 degrees, standard deviation: 8.79 degrees). Thirty percent of eyes had a 10-degree or greater difference in axis measurements, and 13% of eyes had a 20-degree or greater difference in measurements. Analysis by multivariate logistic regression showed higher cylinder powers associated with discrepant corneal power measurements (odds ratio: 3.46, P = .02), and increasing age was associated with discrepant axis measurements (odds ratio: 1.09, P = .03). Overall, there was no significant difference in accuracy predicting postoperative spherical equivalent refraction. CONCLUSIONS: Pentacam and IOLMaster agree well for corneal power but less so for cylinder and axis of astigmatism and thus cannot be used interchangeably.

Complications of femtosecond laser-assisted re-treatment for residual refractive errors after LASIK.

PURPOSE: To report complications of femtosecond laser-assisted re-treatment by the creation of side cuts within the old flaps for residual refractive error after primary LASIK in two patients. METHODS: Case report. RESULTS: Three eyes of two patients had complications with a circumferential sliver of stromal tissue displaced during surgery due to overlap of old and new side cuts. The displaced tissue was repositioned and corneal anatomy was restored. Two of three eyes demonstrated improvement in the uncorrected visual acuity, whereas one eye lost two lines of corrected visual acuity due to loss of tissue at side cut resulting from flap manipulation, which was done at 1 week. CONCLUSIONS: These cases demonstrate a complication of femtosecond laser-enabled side-cut for LASIK enhancement and factors that may lead to this complication and precautions to avoid it.