Change in Visual Acuity of Patients With Fuchs Endothelial Corneal Dystrophy Over 1 Year.

PURPOSE: To determine whether the clinical and paraclinical course of Fuchs endothelial corneal dystrophy (FECD) over 1 year is related to the extent of triplet repetition in the transcription factor 4 (TCF4) gene. METHODS: A prospective study with a 1-year follow-up was conducted. A total of 104 patients (160 eyes) with FECD and an equivalent number of age- and sex-matched control subjects without FECD were included. At inclusion, the corneas were graded using the modified Krachmer grade (KG) and patients were genotyped for the number of trinucleotide repeats (TNRs) in the TCF4 gene by the short tandem repeat assay. Visual acuity, Scheimpflug tomographic features, and the Visual Function and Corneal Health Status using a visual disability instrument were measured on 2 visits at 1-year intervals. RESULTS: KGs ranged from 1 to 6, and 46% of eyes had grades 1 to 4. 71% of the patients harbored TNR expansion (>40) versus 13% in control subjects (P < 0.001). Severity at inclusion was higher in the presence of TNR expansion when considering eyes independently (mean grade ±SD, 4.08 ± 1.42) without TNR expansion and 4.66 ± 1.27 with TNR expansion (P = 0.024). In 1 year, the ETDRS score significantly decreased by -2.97 (95% confidence interval -4.69 to -1.26, P = 0.001) and the ETDRS score with glare by -4.25 (95% confidence interval -6.22 to -2.27, P < 10-5). There was no relationship between the rate of decline and TNR expansion or KG. Central corneal thickness and Visual Function and Corneal Health Status scores did not significantly vary. CONCLUSIONS: It is possible to measure a subtle progression of FECD over a period as short as 1 year. We did not find a relationship between the presence of TNR expansion and the speed of deterioration over 1 year. This work should facilitate the design of future clinical trials on FECD.Trial Registration-URL: ClinicalTrials.gov. Identifier: French Fuchs Follow-up Study (F3S): NCT03974230.

Corneal Toxicity in Patients Treated by BELANTAMAB MAFODOTIN: How to Improve and Facilitate Patients Follow-Up Using Refractive Shift?

Purpose: Multiple myeloma (MM) is the second most common neoplastic blood disease worldwide. Belantamab mafodotin is a new antibody conjugate anti-B-cell maturation antigen effective against refractory myelomas. It induces intracorneal microcysts leading to refractive fluctuations. The aim of this study is to assess the value of monitoring refractive fluctuations based on the location of microcystic-like epithelial changes (MECs) to facilitate patient follow-up. Methods: This observational and multicentric study was conducted using data collected from several French centers contacted through secure email through a standardized data collection table. Results: The fluctuation of objective refraction in spherical equivalent confirms a significant myopic shift from peripheral to central forms. A decrease in the best-corrected visual acuity (BCVA), an increase in keratometry, and an increase in central epithelial pachymetry have also been observed when MECs migrate toward the center. Conclusion: The myopization found in our study in patients with central and paracentral MECs is consistent with current literature. Fluctuations in BCVA, keratometry, and epithelial pachymetry are also consistent. This study is the first real-world study and highlights heterogeneity in follow-up, emphasizing the need to establish multidisciplinary follow-up strategies. The analysis of refractive fluctuations appears to be a reproducible and noninvasive screening method that could facilitate patient follow-up without the need for consultation focused on corneal diseases.

Dropless penetrating keratoplasty using a subconjunctival dexamethasone implant: safety pilot study.

BACKGROUND/AIM: Rejection is the main cause of graft failure after penetrating keratoplasty (PK). Its prevention by repeated instillation of steroid eye-drops has not evolved in decades. Poor adherence and discontinuous nature of eye-drop treatment may explain some PK failures. In a rabbit model, we previously demonstrated that a subconjunctival dexamethasone implant was well tolerated and prevented rejection efficiently in the first 5-6 weeks. This clinical trial investigates its tolerance and safety after PK. METHODS: Single-centre, phase II non-randomised tolerance and safety pilot study (NCT02834260). Designed to analyse the risk of elevated intraocular pressure (IOP), discomfort and resorption time. Fourteen patients with a low rejection risk indication of PK were enrolled between January 2017 and August 2018. The implant was injected in the 12 o'clock position, 5 mm from the limbus, at the end of PK. A steroid eye-drop treatment was planned when implant resorption was complete. Patients were monitored regularly for 12 months: IOP (main outcome measure at 1 month), discomfort and redness scores, implant status, rejection episode and central corneal thickness by optical coherence tomography. An independent data safety monitoring committee verified safety aspects. RESULTS: No increase in IOP or other adverse event related to the implant was observed. Average resorption time was 6 weeks. The switch to steroid eye-drops was uneventful. One patient, included despite preoperative corneal neovascularisation (unintended protocol deviation) experienced a rejection. CONCLUSIONS: This is the first proof of concept that dropless immunosuppression is possible after low rejection risk PK. TRIAL REGISTRATION NUMBER: NCT02834260.

Objective measurement of adherence to topical steroid medication after penetrating keratoplasty using an electronic monitoring aid: A pilot study.

Objectives: Corneal transplantation is the most common transplant worldwide and its success critically depends on the management of corneal graft rejection through topical steroid therapy during the first 12 months after surgery. There is currently no published data on adherence after keratoplasty. This pilot study aims to explore the adherence to topical steroid after penetrating keratoplasty using a smart electronic device. Methods: Thirty patients undergoing penetrating keratoplasty were included to evaluate the adherence to topical dexamethasone medication for 12 months after surgery. Patients received the usual post-transplantation treatment (topical dexamethasone) and follow-up after surgery (day 15, months 1, 2, 3, 4, 5, 6, 9, and 12). Adherence to treatment was monitored using the KaliJAR device (Kali Care, Santa Clara, CA, USA), which recorded the number of single-dose units (SDU) discarded. At control visits, data recorded by the device were compared to the manually count of SDU. Adherence ratio and individual adherence curve were explored for all patients. Results: Data from 27 patients showed a high agreement between adherence ratio calculated based on the device data and obtained from manual counting of the discarded SDU (intraclass coefficient correlation of 0.87 [95% CI: 0.738-0.938]). Mean adherence to the treatment over the 12-month study period was 95.2 ± 4%. Conclusions: Adherence to topical dexamethasone for 12 months after corneal transplantation was high. The connected device was able to record accurately the discarded SDU. This approach would be a particular interest in the early identification and personalized follow-up of poorly adherent patients.

A retrospective study of the efficacy of intense pulsed light delivered by the Lacrystim® for meibomian gland dysfunction therapy.

BACKGROUND: Meibomian gland dysfunction is the most common etiology of dry eye disease worldwide and intense pulsed light appears to be a promising treatment with encouraging results. Lacrystim® is a new IPL device (CE marking in 2019) and no studies have yet been published on it. We propose the first study on this device with an objective assessment of its efficacy and an extended follow-up over 6 months. METHODS: Patients presenting with a dry eye disease (DED) with stable mild to moderate MGD and having received Lacrystim® treatment between june 2019 and june 2020 were included. 3 IPL sessions were performed at D0, D15 and D45 with 4 shots per side at a fluence of 8 mJ/cm2. DED clinical evaluation was performed at D0, D15, D45, 3rd month and 6th month: Oxford scale and break up time, Schirmer test and Ocular Surface Disease Index (OSDI) questionnaire. Lacrydiag® imaging device carried out an objective examination of tear film: interferometry, meibography, tear meniscus height and non-invasive break up time (NIBUT). The primary endpoint was the evolution in NIBUT between the first visit D0 and 3rd month. Data collection was done retrospectively. Statistical analysis was done using a linear mixed-effects model and a non-parametric linear mixed-effects model (R software). RESULTS: Forthy five consecutive patients were included. NIBUT significantly increased between D0 and 3rd month: mean difference of 1.63 seconds, IC95% [0.51; 2.62], (p = 0.002) with a prolonged effect at 6th month. OSDI and OXFORD scores and interferometry were also significantly improved at 3rd month and 6th month. There was no significant change in BUT, Schirmer test and tear meniscus height. No adverse event was noted. CONCLUSIONS: IPL delivered by Lacrystim® appears effective and safe to treat MGD although a randomized controlled trial is needed to validate its results. TRIAL REGISTRATION: This work was approved by a local ethics committee "Terre d'éthique" (institutional review board number: IRBN672019/CHUSTE) and registered on the clinicaltrial.gov website ( NCT04147962 , 01/11/2019).

Detection of refractive photokeratectomy traces during eye banking: impossible with organ culture but possible with an active storage machine: case report.

The detection of corneas operated on for refractive surgery [LASIK or photorefractive keratectomy (PRK)] will become a major concern for eye banks in the coming years because this surgery is often forgotten during the interview with the deceased's relatives. We present here 2 corneas operated on with PKR and stored successively in organ culture (OC) and in the active storage machine (ASM) that restores intraocular pressure, restores the cornea to its original shape, respects transparency and incorporates non-invasive controls. The 2 corneas of a 49-year-old donor operated 17 years earlier by PRK for -2 and -3 diopters myopia were stored in OC for 14 days and then placed in ASM for 48 h. Thickness map and OCT topography were performed under the 2 storage conditions, histology and electron microscopy were then performed. Traces of PRK remained unnoticed in OC while they were evident in ASM with central epithelial anomaly, central thinning and flattening of central keratometry shown by OCT. Histology and ultrastructure confirmed the absence of Bowman's membrane in the center. By placing the cornea under physiological conditions, and in particular by triggering its deswelling and by restoring its natural curvature, the ASM allows effective detection of subtle refractive surgery traces like those present after PRK.

Very early endothelial cell loss after penetrating keratoplasty with organ-cultured corneas.

AIMS: After keratoplasty, postoperative endothelial cell loss is calculated between the eye bank endothelial cell density (ebECD) and the postoperative specular microscopy (SM). To elucidate the very early cell loss, always described after penetrating keratoplasty (PK), we designed two complementary studies. METHODS: (1) Clinical prospective study of 90 consecutive PKs (keratoconus, Fuchs' corneal dystrophy, lattice dystrophy, bullous keratopathy) with organ-cultured corneas and postoperative follow-up by SM at day 5 (D5), D15, month 1 (M1) and M3. This series provided a quantification of the difference between ebECD performed 2 days before graft and very early postoperative ECD. (2) Ten pairs of corneas with comparable ebECD in both corneas and same organ-culture (OC) duration were randomised: one cornea was grafted, and, at the same time, the viable ECD (vECD) of the other was measured after labelling with Hoechst/ethidium/calcein-AM. The relationship between vECD and very early postoperative ECD was studied. RESULTS: vECD at the time of graft did not differ from ECD 5 days after PK, with a difference of 39 (-356; 355) cells/mm2 (median (10°; 90° percentile, p=0.799)), whereas a significant difference of 755 (359; 1146) cells/mm2, corresponding to 28% (95% CI 26 to 30) of cells, was measured between ebECD and ECD 5 days after PK (p<0.001). CONCLUSIONS: In OC, ebECD provided to surgeons significantly overestimate the number of viable ECs grafted to patients. The absence of difference between the vECD at D0 and ECD at D5 indicates that the very early endothelial cell loss is almost negligible in recipients.

Femtosecond laser cutting of endothelial grafts: comparison of endothelial and epithelial applanation.

PURPOSE: Stromal surface quality of endothelial lamellae cut for endothelial keratoplasty with a femtosecond laser (FSL) with epithelial applanation remains disappointing. Applanation of the endothelial side of the cornea, mounted inverted on an artificial chamber, has therefore been proposed to improve cut quality. We compared lamellar quality after FSL cutting using epithelial versus endothelial applanation. METHOD: Lamellae were cut with an FSL from organ-cultured corneas. After randomization, 7 were cut with epithelial applanation and 7 with endothelial applanation. Lamellae of 50-, 75-, and 100-µm thickness were targeted. Thickness was measured by optical coherence tomography before and immediately after cutting. Viable endothelial cell density was quantified immediately after cutting using triple labeling with Hoechst/ethidium/calcein-AM coupled with image analysis with ImageJ. The stromal surface was evaluated by 9 masked observers using semiquantitative scoring of scanning electronic microscopy images. Histology of 2 samples was also analyzed before lamellar detachment. RESULTS: Precision (difference in target/actual thickness) and thickness regularity [coefficient of variation (CV) of 10 measurements] were significantly better with endothelial applanation (precision: 18 µm; range, 10-30; CV: 11%; range, 8-12) than with epithelial applanation (precision: 84 µm; range, 54-107; P = 0.002; CV: 24%; range, 13-47; P = 0.001). Endothelial applanation provided thinner lamellae. However, viable endothelial cell density was significantly lower after endothelial applanation (1183 cells/mm2; range, 787-1725 versus 1688 cells/mm2; range, 1288-2025; P = 0.018). CONCLUSIONS: FSL cutting of endothelial lamellae using endothelial applanation provides thinner more regular grafts with more predictable thickness than with conventional epithelial applanation but strongly reduces the pool of viable endothelial cells.

Comparison of endothelial cell density of organ cultured corneas with cornea donor study.

PURPOSE: Determination of the endothelial cell density (ECD) by eye banks is paramount in donor cornea qualification. Unbiased measurement avoids wastage and grafts with an increased risk of premature failure. Internal calibration of the counting method is essential, but external validation would add an extra stage in the assessment of reliability. In this respect, data published by the multicenter Cornea Donor Study (CDS) in 2005 is a reference. The aim of the study was to compare ECD determined within a single eye bank, which uses calibrated image analysis software designed for transmitted light microscopy images of organ cultured corneas, with the CDS data determined on specular microscopy images of corneas stored at 4°C. METHODS: ECD of consecutive corneas retrieved between 2005 and 2013 was determined after exposure to 0.9% NaCl. More than 300 ECs were counted on 3 fields of the central 8 mm. Endothelial cell boundaries were automatically drawn and verified by a skilled technician who performed all necessary corrections. RESULTS: Three thousand fifty-two corneas were analyzed, of which 48.5% donors were >75 years (CDS upper age limit). Between 10 and 75 years, the ECD varied according to donor age exactly in the same manner as in the CDS, but were consistently higher of 100 ± 25 cells per square millimeter (P < 0.001). CONCLUSIONS: ECD determined by a computer-aided method from transmitted light microscopy images compares favorably with the American CDS reference series. The slight systematic difference on either side of the Atlantic Ocean could be due to (1) differences in counting principles and/or (2) higher shrinkage of the cornea caused by stromal edema in organ culture.

Very early endothelial cell loss after simultaneous corneal autograft and allograft.

PURPOSE: For a better understanding of the very early endothelial cell (EC) loss universally described after all types of keratoplasty, we compared the EC decrease after performing a simultaneous autograft and organ-cultured allograft. METHODS: A 71-year-old woman presented with a central corneal opacity in her left eye and a profoundly amblyopic right eye with a transparent cornea. Both corneas had a normal EC density (ECD). She underwent a left autograft and a right allograft procedure with an organ-cultured cornea, in which the ECD was determined using a calibrated light microscope with image analysis 48 hours before the surgery, that is, just before the final deswelling step with dextran. The postoperative central ECD was determined using specular microscopy on days (D) 1, 2, 3, 4, 5, 15, 20, 30, 60, 90, 120, and 180. RESULTS: Both grafts were uneventful. For the autograft, the pregraft ECD was 2303 cells per square millimeter, and the cell loss was very low, from 4% (D1) to 3% (D180). For the allograft, the pregraft eye bank ECD was 2787, and this decreased by 32% on D5. On D180, the ECD decrease was almost stabilized at 38%. CONCLUSIONS: This difference between the autograft and allograft, both performed in corneas with a normal peripheral endothelial reserve, indicates that the typical very early postoperative decrease in the EC is not caused mainly by surgery-dependent overmortality. It may be mostly artificial, revealing the overestimation of eye bank ECD caused by the technical unfeasibility of strictly considering living ECs and by measuring the ECD several days before grafting. This exceptional case suggests a new paradigm: surgeons graft fewer ECs than they think.