Cornea

Peripheral Hypertrophic Subepithelial Opacities of Corneal Grafts After Deep Anterior Lamellar Keratoplasty Purpose: To investigate possible underlying etiologies of the development of peripheral graft hypertrophic subepithelial opacities (PGHSO) and to evaluate the effects of these opacities on visual outcomes after deep anterior lamellar keratoplasty (DALK). Methods: This prospective, interventional case series enrolled 29 eyes with keratoconus that underwent DALK and developed PGHSO (group 1). The control group consisted of 32 eyes with keratoconus that underwent DALK during the same period and had a clear graft at the final examination (group 2). Possible underlying risk factors for the development of PGHSO were investigated, and postoperative refractive and topographic outcomes were compared between the 2 study groups. Results: Eyes of group 1 had well-defined elevated peripheral subepithelial opacities of the corneal graft, originating from the donor–recipient junction. The central 4-mm area of the graft was clear in all eyes of this group. Compared with the controls, group 1 had flatter grafts at postoperative month 1 and a longer time interval from surgery to initial suture removal. The 2 study groups were comparable in other investigated factors, including the severity of keratoconus, surgical technique, duration of topical steroid use, and donor quality. No significant differences were observed between the case and control groups in postoperative visual acuity and graft surface regularity. Conclusions: Graft flattening during the early postoperative period and prolonged time interval from surgery to initial suture removal might be factors predisposing to the development of PGHSO. This complication did not affect postoperative visual outcomes when the central 4-mm area of the graft remained clear.

Quarter-Descemet Membrane Endothelial Keratoplasty: One- to Two-Year Clinical Outcomes Purpose: To report clinical outcomes of the first Quarter-Descemet membrane endothelial keratoplasty (Quarter-DMEK) case series performed for central Fuchs endothelial corneal dystrophy. Methods: This is a prospective, interventional case series analyzing the clinical outcomes of 19 eyes of 19 patients with central Fuchs endothelial corneal dystrophy, that is, with guttae predominantly in the 6- to 7-mm optical zone, who underwent unilateral Quarter-DMEK at a tertiary referral center. Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), and postoperative complications. Included eyes had up to 2 years of postoperative follow-up. Results: At 6 months postoperatively, all eyes reached a BCVA of ≥20/40 (≥0.5): 18 of 19 eyes (95%) with ≥20/25 (≥0.8) and 9 of 19 eyes (42%) with ≥20/20 (≥1.0). Thereafter, BCVA remained stable up to 2 years postoperatively. The mean donor ECD decreased from 2842 ± 139 cells/mm2 (n = 19) before implantation to 913 ± 434 cells/mm2 (−68%) at 6 months (n = 19), 869 ± 313 cells/mm2 (−70%) at 12 months (n = 18), and 758 ± 225 cells/mm2 (−74%) at 24 months (n = 13) after Quarter-DMEK. Visually significant graft detachment requiring rebubbling occurred in 8 of 19 eyes (42%). Conclusions: Quarter-DMEK surgery yields visual outcomes similar to those of conventional DMEK and may potentially quadruple the availability of endothelial grafts. Further modifications of the graft preparation and the surgical technique may improve clinical outcomes in terms of lower ECD decrease and fewer graft detachments.

Corneal Collagen Cross-Linking With Photoactivated Chromophore for Infectious Keratitis After Penetrating Keratoplasty Purpose: To evaluate the efficacy and safety of corneal collagen cross-linking with photoactivated chromophore (PACK-CXL) plus medical treatment in comparison with the non-CXL group in the management of graft infections after penetrating keratoplasty. Methods: Forty eyes of 40 patients, 18 eyes in the PACK-CXL group and 22 eyes in the non-CXL group, with graft infections were retrospectively reviewed. Patients with microbial keratitis who were resistant to medical treatment for at least 1 week were treated with PACK-CXL in conjunction with medical treatment. The non-CXL group received only medical treatment. Results: The median (interquartile range) size of the infiltrate was 11 (3–12.7) versus 7.5 (3.5–12.7) mm2 (P = 0.37), the epithelization time was 3 (2.7–5) versus 6 (3–11.2) days (P = 0.06), the complete healing time was 23.5 (17.7–33.5) versus 34 (27.7–41.2) days (P = 0.02), and the best-corrected distance visual acuity was 2.5 (0.5–3) versus 2.0 (0.9–3) logarithm of the minimum angle of resolution (P = 0.79) at presentation and 1 (0.3–3) versus 3 (1–3) logarithm of the minimum angle of resolution (P = 0.19) at the final visit for the PACK-CXL and non-CXL groups, respectively. Resolution of infiltrates was observed in 83.3% and 68.2% of cases in the PACK-CXL and non-CXL groups, respectively (P = 0.28). Graft failure was observed in 5 (27.8%) and 12 (54.5%) patients in the PACK-CXL and non-CXL groups, respectively (P = 0.08). Conclusions: PACK-CXL appears to be a promising adjuvant procedure in the management of resistant graft infections by reducing both the duration required for complete healing and rates of graft failure.

Five-Year Graft Survival and Clinical Outcomes of 500 Consecutive Cases After Descemet Membrane Endothelial Keratoplasty Purpose: To report the 5-year graft survival and clinical outcomes after Descemet membrane endothelial keratoplasty (DMEK). Methods: A retrospective, interventional case series was performed at a tertiary referral center. Five hundred eyes of 393 patients that underwent DMEK for Fuchs endothelial corneal dystrophy, bullous keratopathy, failed previous corneal transplants other than DMEK, or other indications were evaluated for graft survival, best-corrected visual acuity (BCVA), endothelial cell density, postoperative complications, and retransplantation rate. Results: Kaplan–Meier analysis demonstrated an estimated survival probability of 0.90 [95% confidence interval, 0.87–0.94] for the entire cohort at 5 years after DMEK. At this time point, 82% of the eyes achieved a BCVA of ≥20/25 (0.8), 54% achieved ≥20/20 (1.0), and 16% achieved ≥20/17 (1.2). BCVA continued to improve from 6 to 36 months after DMEK surgery (P ≤ 0.005) and then remained stable up to 60 months postoperatively (P > 0.08). Preoperative donor endothelial cell density averaged 2530 (±210) cells/mm2 and decreased by 37% at 6 months, 40% at 1 year, and 55% at 5 years after DMEK surgery (P < 0.001 between all follow-up time points). During the study period, allograft rejection episodes developed in 2.8% of the eyes, primary graft failure occurred in 0.2%, and secondary graft failure in 2.8% of the eyes. Re-keratoplasty was required in 8.8% of the eyes. Conclusions: Five-year graft survival after DMEK is high, and visual acuity outcomes remain excellent and are accompanied by a low longer-term complication rate.

Analysis of Compensatory Corneal Epithelial Thickness Changes in Keratoconus Using Corneal Tomography Purpose: To determine patterns of epithelial remodeling in keratoconus and to assess changes in these patterns as the disease progresses. Methods: This is a prospective case series. Patients with keratoconus undergoing corneal collagen crosslinking underwent Scheimpflug imaging before and after epithelial debridement. Analysis was performed to determine maps of epithelial thickness and change in keratometry. Maps were analyzed for patterns, and map SD was quantified. Measures were compared across the patients as grouped by the severity of disease. Results: The study comprised 38 eyes from 30 patients. Patients were stratified using the Amsler–Krumeich classification of keratoconus severity, with 17, 14, and 7 patients in the stage I, stage II, and stage III groups, respectively. A pattern of central epithelial thinning (to approximately 20 μm) with an annulus of epithelial thickening (to approximately 30–40 μm) was demonstrated. Changes were more pronounced in the later stages of the disease, with the average central thickness decreasing from 23 μm in stage I to 18 μm in stage III. Central corneal steepening of 1.5 to 1.9 diopters and peripheral flattening of 1.4 to 2.0 diopters after epithelial debridement were demonstrated. Analysis of map SD revealed a significant difference between stage III patients and patients at earlier stages of disease. Conclusions: The “doughnut pattern” of epithelial remodeling in keratoconus is supported by Scheimpflug imaging. This pattern is demonstrated to partially compensate for central corneal steepening seen in keratoconus.

Psychometric Properties of the Keratoconus Outcomes Research Questionnaire: A Save Sight Keratoconus Registry Study Purpose: The aim of this study was to evaluate the psychometric properties of the Keratoconus Outcomes Research Questionnaire (KORQ) in patients enrolled in the Save Sight Keratoconus Registry. Methods: A cross-sectional study was conducted utilizing prospectively collected web-based registry data. The psychometric properties of the KORQ were assessed using both classical test theory and Rasch analysis. Andrich group rating scale variant of the Rasch analysis was conducted using Winsteps software, Version 3.92.1. Results: The KORQ was completed by 189 patients with keratoconus (men, 67.7%; white, 69.8%; median age 29 years; better eye median values: visual acuity, 75 LogMAR letters; Kmax, 51.3 D; K2, 46.5 D; thinnest pachymetry, 485 μm). Cronbach's α for the “Activity Limitation” and “Symptoms” scales were 0.95 and 0.91, respectively, with both scales free from floor or ceiling effects. On Rasch analysis, the category thresholds were ordered and well-spaced for both scales. The Activity Limitation scale had excellent psychometric properties including person separation index (3.6), unidimensionality (variance explained, 65.4%), fit statistics (<1.3 MnSq), and measurement range (3.6 logits). Similarly, the Symptoms scale had satisfactory psychometric properties including person separation index (2.5), unidimensionality (variance explained, 54.3%), fit statistics (<1.30 MnSq except for 1 item), and measurement range (2.0 logits). Both scales were well targeted to the population and free of differential item functioning. Conclusions: The KORQ is a psychometrically robust patient-reported outcome measure for evaluating quality of life parameters in keratoconus. It enables routine collection and monitoring of meaningful patient-reported outcome data in clinical settings, including registries.

Association Between Early Sjögren Markers and Symptoms and Signs of Dry Eye Purpose: Animal models suggest that early markers of Sjögren syndrome (EMS)—antibodies against salivary protein 1, parotid secretory protein, and carbonic anhydrase 6 (CA6)—are more accurate signals of early Sjögren when compared with classic markers (anti-Ro and anti-La). To further understand the relationship between EMS and dry eye (DE), we compared symptoms and signs of DE in subjects who tested positive versus negative for EMS. Methods: In this cross-sectional study, patients at the Miami Veterans Affairs Eye Clinic who were tested for EMS underwent a standard ocular surface examination. Indications for EMS testing included DE symptoms in combination with dry mouth symptoms, low tear production, corneal staining, or a Sjögren disease-associated autoimmune disease. Statistical tests performed were the χ2 test, Fisher exact test, independent sample t test, and Spearman correlation. Results: Seventy-three percent of 44 patients tested positive for 1 or more EMS. CA6 IgG was most frequently elevated, followed by CA6 IgM and parotid secretory protein IgG. EMS-positive versus EMS-negative subjects were more likely to escalate DE treatment past artificial tears to topical cyclosporine (n = 32, 100% vs. n = 9, 75%, P = 0.02). There were no demographic or comorbidity differences between EMS-positive and EMS-negative subjects, and marker levels did not correlate with more severe tear film measures. Conclusions: Most of the individuals with DE tested positive for 1 or more EMS antibodies, including men and Hispanics. Future studies will be needed to understand how to incorporate EMS data into the care of an individual with DE.

Comparison of Laser Platform Estimation and Objective Measurement of Maximum Ablation Depth Using Scheimpflug Pachymetry in Myopic Femtosecond Laser In Situ Keratomileusis Purpose: To compare the preoperative estimation of maximum ablation depth provided by the laser platform with objective measurement using Scheimpflug pachymetry in myopic femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Methods: This is a prospective study carried out at the Rothschild Foundation, Paris, France. In 89 consecutive myopic eyes (45 patients) treated with FS-LASIK, the maximum ablation depth was calculated by measuring the difference between preoperative and 3-month postoperative measurements in central corneal thickness using Scheimpflug pachymetry (Pentacam HR; Oculus Optikgeräte, Wetzlar, Germany). These values were compared with the preoperative estimation of the maximum ablation depth provided by the laser platform, without nomogram adjustment. Results: We found a strong linear correlation between laser platform estimation of maximum ablation depth and Scheimpflug pachymetry (P < 0.00001). The mean ablation depth measured using Scheimpflug pachymetry was greater than that predicted by the laser platform, with a mean overall difference of 2.15 μm (P < 0.05). Subgroup analysis revealed a difference in ablation depth measurements of 7.1 μm in the high myopia subgroup, which was the only subgroup where the difference remained statistically significant. Conclusions: In myopic FS-LASIK, laser platform estimation of maximum ablation depth correlates well with measurement of maximum ablation depth using Scheimpflug pachymetry and therefore can be used safely.

The Role of Topical Azithromycin in the Treatment of Meibomian Gland Dysfunction Purpose: The efficacy of topical azithromycin (AZ) supplementation to systemic AZ has not been studied. This study evaluates the efficacy of topical AZ supplementation to systemic AZ, warm compresses, artificial tears, and lid scrubs for the treatment of meibomian gland dysfunction (MGD). Methods: Eighty-five patients with stage 4 MGD were enrolled in the study. The patients enrolled into the study were divided into 2 groups. Group 1 comprised 55 patients who received preservative-free topical 1.5% AZ administered as a unit dose, and group 2 comprised 30 patients who did not receive topical AZ. Both groups were prescribed artificial tear eye drops and systemic AZ. Fluorescein tear film breakup time (TBUT), corneal staining, Ocular Surface Disease Index (OSDI) symptom scores, and meibum quality were evaluated at baseline and after 1 and 3 months. Results: The mean age of patients in group 1 was 48.3 ± 13.4 years (25 men and 30 women) and in group 2 was 50.7 ± 10.2 years (12 men and 18 women). After treatment at the first and third month, group 1 showed significant improvement in mean TBUT, mean corneal staining score, meibum quality, and mean OSDI scores compared with baseline (P < 0.05). In group 2, only the OSDI score and meibum quality improved significantly after treatment compared with baseline (P < 0.05). Conclusions: These results demonstrate clinically and statistically greater improvement in MGD-associated signs and symptoms with the addition of topical AZ to the systemic treatment.

Efficacy and Safety of Intense Pulsed Light in Patients With Meibomian Gland Dysfunction—A Randomized, Double-Masked, Sham-Controlled Clinical Trial Purpose: To study the efficacy and safety of intense pulsed light (IPL) in patients with meibomian gland dysfunction (MGD). Methods: This prospective randomized double-masked sham-controlled trial included 114 patients with MGD. Patients were randomized into the IPL or sham group. Either the IPL or sham procedure was performed on days 0, 15, and 45. Ocular Surface Disease Index (OSDI), visual analog scale, visual acuity, tear breakup time, meibum quality and expressibility, meibography grade, ocular surface staining, tear film lipid layer thickness, tear osmolarity, Schirmer test, tear interleukin-1 receptor agonist, and interleukin-6 levels were examined on days 0, 15, and 45 and at months 3 and 6. Subgroup analysis according to stage and the patient's compliance to conventional treatment were also analyzed. Any adverse events during the study were recorded. A multilevel mixed-effect linear regression model was used. P value less than 0.05 was considered statistically significant. Results: At 6 months, tear breakup time, meibum quality grades, expressibility grades, and OSDI were better in the IPL group (5.23 ± 2.91 vs. 3.11 ± 0.99 seconds, P < 0.001; 8.74 ± 4.74 vs. 13.19 ± 5.01, P < 0.001; 0.50 ± 0.67 vs. 1.12 ± 0.70, P < 0.001; 24.29 ± 16.92 vs. 32.71 ± 20.07, P < 0.05). OSDI, meibum quality, and expressibility in the IPL group began to improve at day 15 (P < 0.001), whereas the results in the sham group began to improve at day 45 (P < 0001). No adverse event occurred after IPL. Conclusions: IPL is effective and safe for MGD treatment in all stages regardless of compliance.