Five-Year Risk and Safety Profile of Autologous Serum Eye Drop Therapy.

PURPOSE: To evaluate the risk and safety profile of autologous serum eye drop therapy in clinical routine over a period of 5 years. METHODS: This retrospective study involved all patients treated with autologous serum between July 2014 and December 2019 at a tertiary ophthalmic referral center. The electronic patient record system was searched for all patients with autologous serum eye drop therapy at any time point. These records were subsequently searched for keywords such as infectious keratitis, corneal ulcer, conjunctivitis, or endophthalmitis at any recorded contact. The probability of an association between the therapy with autologous serum eye drops and infectious complications was investigated independently by three corneal specialists and rated as likely, potential, or unlikely. RESULTS: In total, 752 patients were treated with autologous serum eye drops between July 2014 and December 2019. There were 5 384 batches with a total of 107 680 bottles of serum eye drops that had been produced and dispensed for these patients during this period. The records of 291 patient showed a combination of autologous serum therapy and at least one keyword for infectious diseases. In 288 patients, individual case analyses revealed an unlikely association between the therapy and infection, as their infectious episodes occurred either before the start of the therapy, more than 1 month after the therapy ceased, or in the contralateral untreated eye in the case of unilateral therapy. Three cases of infectious keratitis were classified as potentially associated with autologous serum therapy. However, all three patients suffered from chronic anterior eye diseases with a high risk of spontaneous infectious complications independent of therapy with autologous eye drops. None of the infectious events was rated as being likely due to the serum eye drops. CONCLUSIONS: Serum eye drops are often used in patients with severe or chronic anterior eye diseases with an intrinsic risk of infectious diseases. Despite these preexisting risk factors, autologous serum eye drops can be considered safe, even in patients with a compromised ocular surface.

A Clinical Decision Tree to Support Keratoconus Patients Considering Corneal Cross-Linking Combined with Refractive Treatment.

BACKGROUND: To develop a fast and frugal decision tree to identify keratoconus patients most likely to benefit visually from the combination of corneal cross-linking (CXL) with topography-guided photorefractive keratectomy ("CXL plus"). PATIENTS AND METHODS: The outcome of interest was an improvement in uncorrected distance visual acuity (UDVA) by at least two lines at the 12-month follow-up. Preoperative and 12-month follow-up data from patients who received CXL plus (n = 96) and CXL only (n = 96) were used in a recursive partitioning approach to construct a frugal tree with three variables (corneal thickness [>/< 430 um], patient interest in CXL plus [yes/no], and tomographic cylinder [ 3 D]). In addition, we estimated the probability of the outcome from a multivariate logistic regression model for each combination of variables used in the decision tree. RESULTS: In the complete sample, 101/192 (52.6%) patients improved by at least two lines at the 12-month follow-up. Patients affirmative in all three answers had a 75.6% (34/45) probability of gaining at least two lines of improvement in UDVA by CXL plus. The statistical model estimated a 66.0% probability for a successful outcome. CONCLUSION: A fast and frugal tree consisting of three variables can be used to select a patient group with a high likelihood to benefit from CXL plus. The tree is useful in the preoperative counseling of keratoconus patients contemplating the CXL plus option, an intervention that is not fully covered by many health insurances.

Distribution of preoperative angle alpha and angle kappa values in patients undergoing multifocal refractive lens surgery based on a positive contact lens test.

PURPOSE: To assess the preoperative objective angle alpha and angle kappa measurements of patients deciding to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT). METHODS: Retrospective, consecutive case series. Alpha and kappa angles were measured using the iTrace aberrometer. All patients also performed a 1-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the 1-year follow-up. We assessed the preoperative distribution of angle values within MCLT positive and negative patient groups. RESULTS: Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6) and 46.9% were female. In 71 eyes (38 patients), MCLT was positive. Of them, 12 eyes (17%) had an angle alpha and angle kappa ≥ 0.5mm. Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6%) had both angles small (<0.5mm). In the 1-year follow-up, UCVA improved by 0.68 logMAR (SD 0.51; p<0.001) from baseline. Eyes with both small angle alpha and kappa sizes improved by 0.78 logMAR (SD 0.56), as did eyes with high (≥0.5mm) angle sizes (0.82 logMAR (SD 0.53). UCVA of eyes (n=24) with high alpha but low kappa sizes improved less (-0.31 logMAR (SD 0.13; p=0.019)). CONCLUSION: Four out of five patients with a positive MCLT also had correspondingly small angle values. One-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result. One-year visual acuity improvement was substantial and independent from angle sizes.

VEGF-A in Serum and Plasma Rich in Growth Factors (PRGF) Eye Drops.

BACKGROUND: Vascular endothelial growth factor (VEGF)-A, the most abundant subtype of the VEGF family in the eye, plays an important role in corneal homeostasis due to its ability to mediate corneal nerve repair. Repeated intravitreal anti-VEGF injections were shown to significantly reduce corneal nerve density, which might negatively affect corneal homeostasis and lead to a neuropathic dry eye disease. Currently, there are two effective modalities to treat dry eye while supplying VEGF to the ocular surface: serum eye drops (SED) and eye drops manufactured from plasma rich in growth factors (PRGF). The purpose of this study was to measure the VEGF-A concentration in SED and PRGF eye drops. MATERIAL AND METHODS: Ten healthy volunteers donated blood on two separate occasions, 2 - 8 days apart. Thus, a total of 20 blood samples were processed to obtain both SED and PRGF. Concentrations of VEGF-A were quantified by a Simple Plex platform run in triplicate. RESULTS: The VEGF-A concentration in SED and PRGF was very similar between the two blood samples drawn from one individual donor but showed substantial interindividual variability. However, in all 20 samples, VEGF concentrations were substantially higher in SED samples (mean 238.7 ± 146.6 pg/mL) compared to PRGF samples (mean 67.4 ± 46.3 pg/mL). Based upon the analysis of variance (ANOVA) model for the measured concentrations with fixed effects for specimen (SED vs. PRGF) and subject, the mean difference between the SED and PRGF concentration was 168.1 pg/mL (95% confidence interval: [142.4, 193.9], p < 0.001). CONCLUSION: Our study showed that the VEGF concentration was higher in SED than in PRGF. This is an important finding, particularly for potential treatment of dry eye disease in patients with neuropathic eye disease, especially in patients that received repeated anti-VEGF intravitreal injections, or in patients with Sjögren's disease, where the level of VEGF in tears might be pathologically decreased. Hypothetically, VEGF might be needed to restore ocular surface homeostasis. Although growing evidence has shown that VEGF-A plays an important role in corneal homeostasis, only a randomized prospective clinical trial will show whether supplying VEGF-A to the ocular surface might successfully restore the corneal homeostasis and overcome the problem of corneal neuropathy in these patients. For such a trial, based on our results, an undiluted SED should be preferred over a PRGF due to the higher content of VEGF-A.

Effect of Protective Measures on the Risk of SARS-CoV-2 Infection among Eye Clinic Staff Members.

BACKGROUND: Switzerland was strongly affected by the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted in a nationwide lockdown in March 2020. Ophthalmologists were at most risk of contracting a SARS-CoV-2 infection due to their close working distance from patients. The aim of the study is to evaluate the overall effectiveness of protective measures on the risk of SARS-CoV-2 infection among employees in a large public eye hospital. MATERIAL AND METHODS: After lifting the lockdown in April 2020, standard precaution measures were taken, such as no handshaking and the use of operating face masks and a protective plastic shield on slit lamps and diagnostic devices. Only patients with no signs of SARS-CoV-2 disease were seen during the study period. Specific anti-SARS-CoV-2 IgG antibody titers were measured in eye clinic employees at the end of April 2020 (1st test phase) and in January 2021 (2nd test phase). The prevalence of SARS-CoV-2 IgG antibody titers among employees with daily patient contact was compared to staff members with no patient contact. RESULTS: The SARS-CoV-2 prevalence in employees with daily patient contact, with 0% in the 1st phase and 7.4% in the 2nd phase, was not significantly higher than the prevalence in the control group with no patient contact (0.9% in the 1st phase, p = 0.4; and 8.6% in the 2nd phase, p = 0.8). Furthermore, physicians were not at a significantly higher risk of SARS-CoV-2 infection compared to technicians, nurses, or office staff. CONCLUSIONS: This study shows that the abovementioned precaution measurements are effective in preventing transmission of SARS-CoV-2 infection in eye hospitals and enable us to resume practicing ophthalmology in a safe manner.

The Lucerne Protocol for the Production of Autologous Serum Eyedrops.

BACKGROUND: There are a variety of protocols for manufacturing autologous serum (AS) eye drops. The Lucerne protocol for the production of AS eye drops uses a slightly reduced gravitational (g)-force and time for the centrifugation process (2500 × g for 10 minutes), compared to previously published optimised protocols, to obtain high levels of epitheliotropic growth factors (3000 × g for 15 minutes). The goal of this study was to compare the concentrations of growth factors, albumin and lysozyme in autologous serum eye drops manufactured with these protocols. MATERIAL AND METHODS: Blood from 5 healthy volunteers was placed in plastic tubes without an anticoagulant. Tubes from each donor were left in a vertical position for 2 hours at room temperature to facilitate coagulation, followed by centrifugation at either 2500 × g for 10 minutes or at 3000 × g for 15 minutes at room temperature. The serum levels of beta nerve growth factor (ß-NGF), transforming growth factor ß1 (TGF-ß1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A) were measured in triplicate with a multi-analyte Simple Plex platform. The Simple Plex cartridge allows each sample to be run in triplicate for each analyte and prevents any interaction between the antibody components for each biomarker. The serum level of albumin was measured by turbidimetric immunoassay Tina-quant and of lysozyme by single radial immunodiffusion assay. RESULTS: For all analytes, the reduced g-force and centrifugation time did not result in a significant difference in serum levels. CONCLUSIONS: The Lucerne protocol for the production of autologous serum eye drops with reduced g-force and a shorter centrifugation time does not affect the concentrations of the main epitheliotropic growth factors, albumin and lysozyme, in AS eye drops.

Deep Learning Models Used in the Diagnostic Workup of Keratoconus: A Systematic Review and Exploratory Meta-Analysis.

PURPOSE: The prevalence of keratoconus in the general population is reported to be up to 1 of 84. Over the past 2 decades, diagnosis and management evolved rapidly, but keratoconus screening in clinical practice is still challenging and asks for improving the accuracy of keratoconus detection. Deep learning (DL) offers considerable promise for improving the accuracy and speed of medical imaging interpretation. We establish an inventory of studies conducted with DL algorithms that have attempted to diagnose keratoconus. METHODS: This systematic review was conducted according to the recommendations of the PRISMA statement. We searched (Pre-)MEDLINE, Embase, Science Citation Index, Conference Proceedings Citation Index, arXiv document server, and Google Scholar from inception to February 18, 2022. We included studies that evaluated the performance of DL algorithms in the diagnosis of keratoconus. The main outcome was diagnostic performance measured as sensitivity and specificity, and the methodological quality of the included studies was assessed using QUADAS-2. RESULTS: Searches retrieved 4100 nonduplicate records, and we included 19 studies in the qualitative synthesis and 10 studies in the exploratory meta-analysis. The overall study quality was limited because of poor reporting of patient selection and the use of inadequate reference standards. We found a pooled sensitivity of 97.5% (95% confidence interval, 93.6%-99.0%) and a pooled specificity of 97.2% (95% confidence interval, 85.7%-99.5%) for topography images as input. CONCLUSIONS: Our systematic review found that the overall diagnostic performance of DL models to detect keratoconus was good, but the methodological quality of included studies was modest.

The effect of a video tutorial to improve patients' keratoconus knowledge - a randomized controlled trial and meta-analysis of published reports.

Objective: To investigate whether a video tutorial, highlighting important aspects of keratoconus provided prior to a scheduled follow-up consultation, has a specific effect on patients' knowledge after the consultation. Methods and Analysis: Single center, randomized controlled trial registered on ISRCTN registry (number ISCTN75317089, https://doi.org/10.1186/ISRCTN75317089). Consenting eligible keratoconus patients were randomly assigned to either receive a conventional face-to-face consultation (control group) or to an additional video tutorial (interventional group) on definition, risk factors and treatment options provided prior to the consultation. The main outcome measure was the difference of knowledge assessed by a questionnaire after the consultation. Of each participant, clinical characteristics, highest educational level and medical background were obtained. We also performed a meta-analysis of published reports assessing knowledge improvement by video-based patient education. Results: We assigned 22 patients to the interventional and 21 patients to the control group. Mean age was 29.0 years (SD 11.6), 8/43 (18.6%) were female and median disease duration was 2.5 years (interquartile range: 2-5years). Compared to the control group, knowledge was 12.0% (95%CI: 5.8%-18.2%; p<0.001) higher in the interventional group. Subjects with a university degree scored 6.8% (95%CI: 3.8%-13.3%; p=0.038) higher. There was no interaction between video information and university degree. Other parameters were not associated with patient knowledge. The meta-analysis of 566 subjects enrolled in 6 studies revealed a standardized mean difference in favor of video-based education of 0.47 (95% CI: 0.30-0.64; p<0.004). Conclusion: The results suggest that supplementary video information embedded in the clinical management of keratoconus, helps conveying relevant disease knowledge.