Prospective analysis of anatomic features predisposing patients to intraoperative floppy iris syndrome.

PURPOSE: To aid preoperative risk assessment by identifying anatomic parameters corresponding with a higher risk of intraoperative floppy iris syndrome (IFIS) during cataract surgery. METHODS: Prospective cohort study of 55 patients with α1-adrenergic receptor antagonist (α1-ARA) treatment and 55 controls undergoing cataract surgery. Anterior segment optical coherence tomography (AS-OCT), video pupilometer, and biometry measurements were performed preoperatively and analyzed regarding anatomic parameters that corresponded with a higher rate of IFIS. Those statistically significant parameters were evaluated with logistic regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Pupil diameter was significantly smaller in patients who developed IFIS compared to those who did not develop IFIS (AS-OCT 3.29 ± 0.85 vs. 3.63 ± 0.68, p = 0.03; Pupilometer 3.56 ± 0,87 vs. 3.95 ± 0.67, p = 0.02). Biometric evaluation revealed shallower anterior chambers in the IFIS group (ACD 3.12 ± 0.40 vs. 3.32 ± 0.42, p = 0.02). Cutoff values for 50% IFIS probability (p = 0.5) were PD = 3.18 mm for pupil diameter and ACD = 2.93 mm for anterior chamber depth. ROC curves of combined parameters were calculated for α1-ARA medication with pupil diameter and anterior chamber depth, which yielded an AUC of 0.75 for all IFIS grades. CONCLUSION: The combination of biometric parameters with history of α1-ARA medication can improve assessment of risk stratification for IFIS incidence during cataract surgery.

Long-term impact of delayed follow-up due to COVID-19 lockdown on patients with neovascular age-related macular degeneration.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in 2020 outpatient care of neovascular age-related macular degeneration (nAMD) patients was severely reduced due to lockdown. Missed visits are known to be detrimental to patients in need of continued anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVIs). The purpose of the study was to assess the effect of a month-long pause of regular visits and anti-VEGF IVIs in nAMD patients. METHODS: A retrospective study was performed. Patients were treated in a pro re nata ("as needed") scheme. Distance (logMAR) and near (logRAD) visual acuity (VA), optical coherence tomography, delay between planned and actual visit date and the indication for IVI were assessed for 3 continous visits in the 6 months before lockdown (V-3, -2, -1) and the 2 visits after lockdown (V0, V + 1). For analysis of long-term impact, records for visits 1 years before and after lockdown (V-3, V + 2) were gathered. RESULTS: We included 166 patients (120 female, 46 male) with a median (range) age of 80.88 (59.8-99.36) years. Compared to V-1, distance VA was significantly worse at both V0 (0.27 ± 0.21 vs 0.31 ± 0.23 logMAR, p < 0.001) and V + 1 (0.27 ± 0.21 vs 0.30 ± 0.23 logMAR, p = 0.021). Near VA was significantly worse at both V0 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.037) and V + 1 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.02). Visit delay (VD) at V0 was significantly longer than at V + 1 (30.81 ± 20.44 vs 2.02 ± 6.79 days, p < 0.0001). Linear regression analysis showed a significant association between visit delay and a reduction of near VA between V-1 and V + 1 (p = 0.0223). There was a significant loss of distance VA (p = 0.02) in the year after the lockdown period (n = 125) compared to the year before. Loss of reading acuity was not significantly increased (p = 0.3). One year post lockdown, there was no correlation between VA change and visit delay after lockdown (p > 0.05). CONCLUSIONS: In nAMD patients whose visits and treatment were paused for a month during the first wave of the COVID-19 pandemic, we found a loss of VA immediately after lockdown, which persisted during follow-up despite re-established anti-VEGF treatment. In the short term, length of delay was predictive for loss of reading VA. The comparison of development of VA during the year before and after the lockdown showed a progression of nAMD related VA loss which may have been accelerated by the disruption of regular visits and treatment. TRIAL REGISTRATION: This article does not report the outcome of a health care intervention. This retrospective study was therefore not registered in a clinical trials database.

The relationship between patient satisfaction and visual and optical outcome after bilateral implantation of an extended depth of focus multifocal intraocular lens.

Purpose: To evaluate patient satisfaction after implantation of the Tecnis Symfony multifocal intraocular lens (MIOL). Methods: 120 eyes of 60 subjects with senile cataract were bilaterally implanted with the Tecnis Symfony IOL. Follow-up examination was performed 6 months postoperatively. Main outcome measures included uncorrected and corrected distance and near visual acuity, manifest refraction, and visual quality metrics. According to their subjective symptoms patient were divided in two groups: satisfied and unsatisfied. Results: Uncorrected intermediate (0.15 â€‹± â€‹0.11 vs 0.18 â€‹± â€‹0.01, P â€‹= â€‹0.04) and near (0.26 â€‹± â€‹0.12 vs 0.31 â€‹± â€‹0.11, P â€‹= â€‹0.04) (UIVA, UNVA) log MAR visual acuity was significantly better, cylindrical error less (0.31 â€‹± â€‹0.36 vs 0.67 â€‹± â€‹0.29, P â€‹= â€‹0.05), axial length (AL) smaller (23.68 â€‹± â€‹1.3 vs 24.22 â€‹± â€‹1.6, P â€‹= â€‹0.05), Strehl ratio higher (0.08 â€‹± â€‹0.08 vs 0.05 â€‹± â€‹0.04, P â€‹= â€‹0.03) and mesopic pupil larger (4.3 â€‹± â€‹1.1 vs 3.7 â€‹± â€‹1.05, P â€‹= â€‹0.01) among satisfied patients.Residual cylinder, Strehl ratio, halos, mesopic pupil diameter and UNVA were significant predictors of patient satisfaction. Uncorrected distance visual acuity, higher order Strehl ratio and pupil diameter were significant predictors of halos. Near visual acuity significantly correlated (P â€‹= â€‹0.018, R â€‹= â€‹0.22) with axial length. Conclusions: Uncorrected cylindrical error, poor reading quality, larger pupil and halos seem to be the most disturbing factors for patients implanted with the Tecnis Symfony IOL.

Quality of life in patients with glaucoma assessed by 39-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-39).

PURPOSE: The purpose of the study was to evaluate glaucoma patients' quality of life (QoL) as measured by National Eye Institute Visual Functioning Questionnaire (NEI VFQ-39) and to examine the influence of patient characteristics and disease stage measured by visual field loss on QoL. METHODS: A prospective survey of patients with an established diagnosis of glaucoma without concomitant eye disease was conducted. Patients completed a validated German translation of the NEI VFQ-39 questionnaire. Visual field defects were graded using simplified Hodapp's classification. VFQ-39 scores were compared between groups. RESULTS: We included 60 patients, 28 of whom were classified as early, 16 as moderate, and 16 as advanced stage glaucoma. No differences were found in sex, visual acuity of the better eye, near visual acuity, treatment type, and VFQ rating for "General health" between groups. In the advanced group, VFQ-39 (p = 0.01) and VFQ-25 (p = 0.01) composite scores were significantly lower than in the early group. In addition, distance visual acuity (worse eye) was significantly worse in the advanced than in early stage patients (p = 0.04, Table 4). Patients with advanced glaucoma had significantly lower VFQ-39 subscale scores for "General vision" (p = 0.023), "Near activities" (p = 0.02), "Distance activities" (p = 0.003), "Mental health" (p = 0.008), "Driving" (p = 0.011), and "Peripheral vision" (p = 0.017) than early glaucoma patients. Patients with moderate glaucoma had significantly lower scores for "Distance activities" (p = 0.028) than early stage glaucoma patients. VFI (better eye: r = 0.65, worse eye: r = 0.5) and MD (better eye: r = 0.6, worse eye: r = 0.49) were significantly (p < 0.001) correlated with VFQ-39. Correlations of VFQ-39 with age, VFI intereye difference, distance, or near visual acuity were not significant. CONCLUSION: Compared to patients with early glaucoma, patients with moderate stage glaucoma reported higher difficulty with distance activities (e.g. navigating an urban environment, watching television). Patients with advanced stage glaucoma reported lower VFQ-39 composite and subscale scores relevant to topics of general vision complaints, difficulties with near work and finding things, navigating urban outdoor environments, and watching television; worries and frustrations with vision difficulties; and difficulty driving and noticing objects off to the side of footpaths. Visual field indices MD and VFI were strongly correlated with QoL as assessed by VFQ-39. VA was not correlated with QoL. In patients with moderate or advanced glaucoma, QoL may be significantly impacted by glaucomatous visual field defects even when visual acuity is preserved.

Prevalence of SARS-CoV-2 infection in patients presenting for intravitreal injection.

AIM: Due to the coronavirus disease 2019 (COVID-19) pandemic, nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great concern to clinicians of all specialties. Currently there are no published data available on the prevalence of the infection in ophthalmology patients presenting for intravitreal injection (IVI). The purpose of this retrospective study was to estimate the prevalence of SARS-CoV­2 infection in patients presenting for IVI at our hospital. METHODS: Patients presenting for IVI in April 2020 at our hospital who had been screened for SARS-CoV­2 infection using nasopharyngeal and oropharyngeal specimen for real-time reverse transcription polymerase chain reaction analysis were included in a retrospective study. To assess the representativity of this sample for IVI patients, characteristics were compared with patients presenting for IVI during March-April 2019. RESULTS: The study included 279 patients and 319 historic control patients. Of 277 valid test results, one SARS-CoV­2 positive patient was found, resulting in a carrier rate of 0.36% with a 95% Clopper-Pearson confidence interval of 0.01-1.99%. No differences in sex (57.7% vs. 59.9% female, p = 0.650), age (77.63 ± 10.29 vs. 77.59 ± 10.94 years, p = 0.962), and region of residence were found between groups. CONCLUSION: The study provides an estimate for the prevalence of SARS-CoV­2 infection in asymptomatic patients presenting for IVI. While these data may be used as a baseline, further research is needed to assess the development of SARS-CoV­2 prevalence in this patient group in order to support risk assessment and infection prevention strategies.

Repeatability and Reproducibility of Total Retinal Blood Flow Measurements Using Bi-Directional Doppler OCT.

Purpose: To investigate the repeatability and reproducibility of total retinal blood flow measurements using a custom-built dual-beam bidirectional Doppler optical coherence tomography (OCT) system in healthy subjects. Methods: Repeatability and reproducibility were analyzed in 10 and 34 healthy subjects, respectively. For repeatability, measurements were taken twice within 30 minutes, for reproducibility, twice within two to five weeks. Two analysis approaches were compared for calculation of absolute blood velocities: a previously published approach resulting in values for total arterial (QA,abs) and total venous blood flow (QV,abs) and a novel approach taking into account that there is a fixed relation between the phase shift in the two OCT channels (QA,new, QV,new). Repeatability and reproducibility were quantified using intraclass correlation coefficients (ICCs). Results: For QA,abs and QV,abs, ICC values between 0.78 and 0.84 were obtained. QA,new and QV,new values revealed better repeatability and reproducibility as compared to the convential appoach. Repeatability ICCs for QA,new and QV,new were between 0.91 and 0.93, and reproducibility ICCs were between 0.87 and 0.91 indicating excellent reproducibility. Good agreement was observed between total retinal blood flow values as measured from retinal arteries and retinal veins. Conclusions: Measurement of total retinal blood flow using dual-beam Doppler OCT shows excellent reproducibility, which can further be improved by using a novel algorithm for calculating blood velocities in retinal vessels. Translational Relevance: Our data indicate that dual-beam Doppler OCT can be used for longitudinal studies. Hence, quantitative retinal blood flow may be established as a biomarker for progression vascular eye diseases.

A pilot study to assess the effect of a three-month vitamin supplementation containing L-methylfolate on systemic homocysteine plasma concentrations and retinal blood flow in patients with diabetes.

Purpose: The aim of the present study was to investigate the effect of a three-month dietary supplementation with a methylfolate formulation on homocysteine plasma concentrations and ocular blood flow parameters in patients with diabetes. Methods: Twenty-four patients with diabetes received a dietary supplement (Oculofolin, Aprofol AG, Switzerland) containing 900 µg L­methylfolate (levomefolate calcium or [6S]-5-methyltetrahydrofolic acid, calcium salt), methylcobalamin, and other ingredients for three consecutive months. The patients' plasma homocysteine concentration and retinal blood flow were assessed at baseline and after three months of folate intake. Retinal blood flow was measured using a custom-built dual-beam Doppler optical coherence tomography (OCT) system. In addition, flicker-induced retinal vasodilatation was assessed by means of a commercially available dynamic vessel analyzer (IMEDOS, Jena, Germany). Results: Supplementation was well tolerated by all patients. After three months, plasma homocysteine concentration significantly decreased from 14.2 ± 9.3 to 9.6 ± 6.6 µmol/L (p < 0.001). In addition, a tendency toward an increased total retinal blood flow from 36.8 ± 12.9 to 39.2 ± 10.8 µl/min was observed, but this effect did not reach the level of significance (p = 0.11). Supplementation had no effect on retinal vessel diameter or flicker-induced vasodilatation. Conclusions: The present data show that a three-month intake of a dietary supplement containing methylfolate can significantly reduce blood homocysteine levels in patients with diabetes. This is of importance because higher homocysteine plasma levels have been found to be associated with an increased risk of vascular associated systemic diseases and eye diseases. Whether systemic methylfolate supplementation affects retinal perfusion must be studied in a larger population.

Anatomical and functional changes in the retina in patients with Alzheimer's disease and mild cognitive impairment.

PURPOSE: There is evidence that mild cognitive impairment (MCI) or Alzheimer's disease (AD) is accompanied by alterations in the retina. The current study was performed to investigate structural and functional changes in patients with systemic neurodegenerative disease. METHODS: A total of 47 patients with either MCI or AD and 43 healthy age- and sex-matched control subjects were included. Inclusion criteria for MCI were abnormal memory function and a mini-mental state examination (MMSE) score >26 points, for patients with AD a diagnosis of probable AD of mild to moderate degree and an MMSE score in the range of 20-26. Retinal blood flow was measured using a Doppler optical coherence tomography (OCT) system. Retinal vessel diameter, oxygen saturation and flicker-induced vasodilatation were measured using a Vessel Analyzer. Retinal nerve fibre layer thickness (RNFLT) was assessed using an OCT system. RESULTS: Global RNFLT was lower in patients compared to healthy controls (93.7 ± 12.8 µm versus 99.1 ± 9.0 µm, p = 0.02). The same was found in regards to retinal arterial blood flow, which was 9.3 ± 2.4 and 12.3 ± 3.2 µl/min in the patient and control groups, respectively (p < 0.001). Mean retinal arterial diameter was reduced in patients (76.0 ± 8.9 µm versus 80.6 ± 8.0 µm, p = 0.03). Arteriovenous difference in oxygen saturation was lower in patients (20.4 ± 5.1% versus 23.5 ± 4.0%, p < 0.01). No difference in the flicker response was observed. CONCLUSION: In patients with MCI and AD, arteriovenous difference in oxygen saturation, retinal blood flow and arterial vessel diameter was reduced. No difference was found in flicker response between groups. This indicates alterations in retinal oxygen metabolism in patients with neurodegenerative disease.

Changes in Retinal Blood Flow in Response to an Experimental Increase in IOP in Healthy Participants as Assessed With Doppler Optical Coherence Tomography.

Purpose: Blood flow autoregulation is an intrinsic mechanism of the healthy retinal vasculature to keep blood flow constant when ocular perfusion pressure (OPP) is changed. In the present study, we set out to investigate retinal blood flow in response to an experimental decrease in OPP in healthy participants using Doppler optical coherence tomography. Methods: Fifteen healthy participants aged between 22 and 31 years (mean, 27 ± 3 years) were included in the present open study. IOP was increased stepwise via the suction cup method to induce a decrease in OPP. Retinal blood flow in arteries and veins was assessed using a custom-built Doppler optical coherence tomography system and pressure-flow relationships were calculated to assess autoregulation. Results: Suction cup application induced a pronounced increase in IOP with a maximum value of 50.5 ± 8.0 mm Hg at the highest level of suction. Pressure-flow relationships revealed that blood flow was autoregulated until the OPP was decreased by approximately 21 mm Hg and started to decrease significantly when the OPP was reduced by 30 mm Hg. Retinal blood flow at the last suction period decreased at a maximum of -57.0 ± 22.3% and 65.2 ± 15.4% in retinal arteries and retinal veins, respectively. These changes in retinal blood flow were less pronounced than the decrease in OPP (-75.2 ± 19.2%), indicating retinal autoregulation. Conclusions: The results of the present study confirm that retinal blood flow is autoregulated in response to changes in the OPP. Doppler optical coherence tomography has the potential to become a clinical tool for the investigation of retinal blood flow autoregulation in the future, because of its ability to assess the blood velocities and diameter of the retinal vessels parallel and therefore also their blood flow in absolute values. (Clinicaltrials.gov number NCT03398616).

The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects-A Randomized Clinical Trial.

It has been hypothesized that besides its intraocular pressure (IOP) lowering potential, tetrahydrocannabinol (THC) may also improve ocular hemodynamics. The aim of the present study was to investigate whether single oral administration of dronabinol, a synthetic THC, alters optic nerve head blood flow (ONHBF) and its regulation in healthy subjects. The study was carried out in a randomized, placebo-controlled, double-masked, two-way crossover design in 24 healthy subjects. For each study participant, 2 study days were scheduled, on which they either received capsules containing 5 mg dronabinol or placebo. ONHBF was measured with laser Doppler flowmetry at rest and while the study participants performed isometric exercise for 6 minutes to increase mean arterial blood pressure (MAP). This was repeated 1 hour after drug intake. Ocular perfusion pressure (OPP) was calculated as 2/3MAP-IOP. Dronabinol was well tolerated and no cannabinoid-related psychoactive effects were reported. Neither administration of dronabinol nor placebo had an effect on IOP, MAP, or OPP. In contrast, dronabinol significantly increased ONHBF at rest by 9.5 ± 8.1%, whereas placebo did not show a change in ONHBF (0.3 ± 7.4% vs. baseline, P < 0.001 between study days). Dronabinol did not alter the autoregulatory response of ONHBF to isometric exercise. In conclusion, the present data indicate that low-dose dronabinol increases ONHBF in healthy subjects without affecting IOP, OPP, or inducing psychoactive side effects. In addition, dronabinol does not alter the autoregulatory response of ONHBF to an experimental increase in OPP. Further studies are needed to investigate whether this effect can also be observed in patients with glaucoma.

Influence of Perfluorohexyloctane Eye Drops on Tear Film Thickness in Patients with Mild to Moderate Dry Eye Disease: A Randomized Controlled Clinical Trial.

Purpose: The aim of this mechanistic clinical study was to explore the effect of water-free perfluorohexyloctane eye drops on tear film thickness (TFT) in patients with dry eye disease (DED). Methods: Forty-eight patients with mild to moderate DED participated in this randomized, single-masked, observer-blinded parallel group study in a 1:1 ratio to receive either perfluorohexyloctane or unpreserved 0.9% saline solution (Hydrabak®, Thea, France) eye drops 4 times daily in both eyes for 4 weeks. A custom-built ultrahigh-resolution optical coherence tomography system was used to measure TFT. Furthermore, evaluation of lipid layer thickness (LLT) and noninvasive tear film breakup time, as well as standard clinical tests for signs and symptoms of DED were performed. Results: Mean TFT and LLT at baseline were comparable between the 2 treatment groups. After a single drop instillation, perfluorohexyloctane eye drops temporarily increased TFT immediately. After multiple dosing, perfluorohexyloctane eye drops gradually increased TFT over time with a maximum effect at the end of the study (least square mean difference: 6.42%; P = 0.0142 at week 4). LLT values measured before drop instillation showed a more prominent increase in LLT for perfluorohexyloctane eye drops (13.36% ± 26.33% vs. 3.21% ± 28.65%). All other parameters got better in both treatment groups with no statistical difference between groups. Conclusions: These results demonstrate that perfluorohexyloctane eye drops increase TFT as well as LLT over time. These tear film reestablishing attributes are in line with the mode of action of perfluorohexyloctane eye drops to avoid evaporation through stabilization of the lipid layer.

Correction to: Topical Low Dose Preservative-Free Hydrocortisone Reduces Signs and Symptoms in Patients with Chronic Dry Eye: A Randomized Clinical Trial.

The article "Topical Low Dose Preservative-Free Hydrocortisone Reduces Signs and Symptoms in Patients with Chronic Dry Eye: A Randomized Clinical Trial", written by Martin Kallab, Stephan Szegedi, Nikolaus Hommer, Hannes Stegmann, Semira Kaya, René M. Werkmeister, Doreen Schmidl, Leopold Schmetterer, Gerhard Garhöfer was originally published electronically on the publisher's internet portal (currently SpringerLink) on November 19, 2019 without open access.

Topical Low Dose Preservative-Free Hydrocortisone Reduces Signs and Symptoms in Patients with Chronic Dry Eye: A Randomized Clinical Trial.

PURPOSE: Dry eye disease (DED) is a highly prevalent ocular condition with a significant burden on affected patients. Regardless of the underlying etiology, DED is associated with increased ocular surface inflammation. We investigated the safety and efficacy of a short-term treatment with topical low dose hydrocortisone in patients with chronic DED and ocular surface inflammation. METHODS: A total of 60 patients (mean age 51 ± 14 years) with chronic DED and conjunctival hyperemia greater than grade 2 on the Efron scale were included. Patients were randomized to receive either preservative-free hydrocortisone 0.335% (Softacort, Laboratories Thea, France) for 12 days four times daily followed by 2 days twice daily instillation (intense treatment group) or 8 days three times daily followed by 3 days twice daily treatment (standard treatment group). Ocular redness was assessed at baseline, day 14, and day 28. Measurement of intraocular pressure (IOP) and clinical tests to assess signs and symptoms of DED were performed. RESULTS: Conjunctival hyperemia and Ocular Surface Disease Index (OSDI) significantly decreased in both treatment groups (p < 0.001 each) after hydrocortisone treatment. A significant increase in tear film thickness was seen 4 weeks after treatment start (p = 0.03 and p = 0.04, respectively). IOP did not change in either of the two treatment groups (p = 0.45). CONCLUSION: Treatment with low dose hydrocortisone 0.335% reduced ocular inflammation and decreased OSDI score. No change in IOP was observed in either of the two treatment schedules. Because of its good safety profile, low dose hydrocortisone may be an interesting alternative to standard corticosteroid treatment in DED. FUNDING: Laboratories Thea. TRIAL REGISTRATION: Clinicaltrials.gov registry: NCT03907865.

Age-Related Decline of Retinal Oxygen Extraction in Healthy Subjects.

Purpose: To investigate the age-dependence of total retinal blood flow and total retinal oxygen extraction in healthy subjects and determine their possible correlations with structural optical coherence tomography (OCT) parameters. Methods: This observational cross-sectional study consisted of 68 healthy subjects (mean ± SD age, 45.6 ± 16.3 years; 47% female). Total retinal oxygen extraction was calculated based on measurement of total retinal blood flow using bi-directional Doppler OCT and measurement of oxygen saturation using spectroscopic reflectometry. Retinal nerve fiber layer thickness was measured using OCT, and the total number of retinal ganglion cells was estimated based on a previous published model. Correlation of these parameters with age was studied and the association between structural OCT parameters and hemodynamic vascular parameters was calculated. Results: Both structural and vascular parameters showed a significant decline with increasing age. The correlation coefficients were between r = -0.25 and r = -0.41. Furthermore, structural and vascular parameters were significantly correlated with each other. The strongest association was found between the level of total retinal oxygen extraction and the number of retinal ganglion cells (r = 0.75, P < 0.001). Conclusions: We showed that there was an age-related decline of retinal oxygen extraction. Levels of retinal oxygen extraction are correlated to retinal nerve fiber layer thickness and number of retinal ganglion cells. Our data partially explain the wide inter-individual variability in retinal blood flow values in healthy subjects. Longitudinal studies are required to study the time course of vascular and neuronal loss in humans.

Effect of Single Instillation of Two Hyaluronic Acid-Based Topical Lubricants on Tear Film Thickness in Patients with Dry Eye Syndrome.

PURPOSE: This study investigated the effect of single administration of 2 different hyaluronic acid-based topical lubricants on tear film thickness (TFT) in patients with moderate-to-severe dry eye disease (DED). METHODS: Sixty patients were randomized to receive eye drops containing unpreserved sodium hyaluronate, triglycerides, and phospholipids (HTP), unpreserved sodium hyaluronate (HA), or unpreserved sodium chloride (NaCl). TFT and lipid layer thickness (LLT) were assessed before and at defined time points after single instillation with a custom-built ultrahigh-resolution optical coherence tomography system and a white light interferometer. Standard tests for DED such as a visual analogue scale (VAS), corneal fluorescein staining (CFS), Schirmer I test, and tear break-up time (BUT) were performed. RESULTS: The time course in TFT was significantly different between the 3 administered agents (P < 0.001). Single administration of HTP significantly increased TFT over a period of 40 min, an increase in TFT over 20 min was observed after instillation of HA, whereas NaCl had no effect. No significant difference in the change in BUT, CFS, or LLT was observed between the 3 groups (P = 0.57, 0.97, and 0.86, respectively). A significant improvement in subjective symptoms (VAS) was found after single instillation of HTP (P = 0.03 vs. baseline) and HA, but not after administration of NaCl (P = 0.03, P < 0.01, and P = 0.08 vs. baseline, respectively, P = 0.57 between groups). CONCLUSIONS: Single administration of HTP and HA significantly increased TFT showing a longer residence time and improved subjective symptoms, whereas instillation of NaCl had no effect. Long-term studies with multiple instillations will be necessary to further investigate the effect of the tested products on the clinical outcome. ClinicalTrials.gov ID: NCT03161080.

Effect of a Matrix Therapy Agent on Corneal Epithelial Healing After Standard Collagen Cross-linking in Patients With Keratoconus: A Randomized Clinical Trial.

IMPORTANCE: Corneal abrasions are frequent after standard (epithelium-off [epi-off]) corneal collagen cross-linking (CXL) in patients with progressive keratoconus. A new matrix therapy agent (ReGeneraTing Agent [RGTA]) has been developed to promote corneal wound healing. OBJECTIVE: To assess the effect of the new type of matrix therapy agent on corneal wound healing after epi-off CXL in patients with keratoconus. DESIGN, SETTING, AND PARTICIPANTS: This double-masked randomized clinical trial enrolled 40 patients with keratoconus undergoing epi-off CXL from July 18, 2014, to October 21, 2015, when the last follow-up was completed. The analysis of the intention-to-treat population was performed at the Department of Clinical Pharmacology in cooperation with the Center for Medical Physics and Biomedical Engineering and the Department of Ophthalmology and Optometry of the Medical University of Vienna. INTERVENTIONS: Patients were randomized to receive the matrix therapy agent or hyaluronic acid-containing eyedrops, 0.1%, every other day starting immediately after surgery. The size of the corneal defect was measured using ultrahigh-resolution optical coherence tomography (OCT) and slitlamp photography (SLP) with fluorescein staining. MAIN OUTCOMES AND MEASURES: Corneal wound healing rate, defined as the size of the defect over time. RESULTS: Among the 40 patients undergoing epi-off CXL (31 men; 9 women; mean [SD] age, 31 [10] years), wound healing was significantly faster in the matrix therapy agent group compared with the hyaluronic acid group (4.4 vs 6.1 days; mean difference, 1.7 days; 95% CI, 0.25-3.15 days; P = .008). The defect size was smaller in the matrix therapy agent group than in the hyaluronic acid group as measured with OCT (12.4 vs 23.9 mm2; mean difference, 11.6 mm2; 95% CI, 0.8-23.5 mm2; P = .045) and SLP (11.9 vs 23.5 mm2; mean difference, 11. 6 mm2; 95% CI, 1.3-22.9 mm2; P = .03). A correlation between the defect size measured with OCT and SLP was found (r = 0.89; P < .001). No ocular or serious adverse events occurred. CONCLUSIONS AND RELEVANCE: Use of a new matrix therapy agent appears to improve corneal wound healing after CXL in patients with keratoconus. Monitoring of corneal wound healing using ultrahigh-resolution OCT might be an attractive alternative to SLP because OCT provides an objective and 3-dimensional evaluation of the corneal defect. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02119039.