Human selection bias drives the linear nature of the more ground truth effect in explainable deep learning optical coherence tomography image segmentation.

Supervised deep learning (DL) algorithms are highly dependent on training data for which human graders are assigned, for example, for optical coherence tomography (OCT) image annotation. Despite the tremendous success of DL, due to human judgment, these ground truth labels can be inaccurate and/or ambiguous and cause a human selection bias. We therefore investigated the impact of the size of the ground truth and variable numbers of graders on the predictive performance of the same DL architecture and repeated each experiment three times. The largest training dataset delivered a prediction performance close to that of human experts. All DL systems utilized were highly consistent. Nevertheless, the DL under-performers could not achieve any further autonomous improvement even after repeated training. Furthermore, a quantifiable linear relationship between ground truth ambiguity and the beneficial effect of having a larger amount of ground truth data was detected and marked as the more-ground-truth effect.

Single versus Double PreserFlo MicroShunt Implantation in Glaucoma Patients: A Retrospective Cohort Study.

INTRODUCTION: The aim of this study was to describe and evaluate double PreserFlo MicroShunt implantation as a modified micro-invasive glaucoma surgery technique and to retrospectively compare the outcomes in a cohort of glaucoma patients with single or double implantation. MATERIALS AND METHODS: A retrospective data analysis of 57 glaucoma patients who consecutively underwent PreserFlo implantation was performed. Medical records were examined for patients' demographics, glaucoma type, intraocular pressure (IOP), medication, complications, and re-interventions. Two groups with single (n = 29) or double (n = 28) implantation were formed, and the outcomes were compared. In cases of two-stage double implantation (n = 17), the courses of the initial and the second implantations were compared. RESULTS: Mean preoperative IOP was significantly higher in the double compared to the single implantation group (29.4 ± 10.0 mm Hg; 21.7 ± 8.2 mm Hg; p = 0.003). Postoperatively, IOP was significantly lower in the double implantation group at various time-points (day 1, week 1, months 3 and 6; all p < 0.021). In the subgroup with two-stage procedures, mean preoperative IOP was 24.5 ± 8.5 mm Hg and 29.8 ± 10.1 mm Hg, respectively (p = 0.128). While immediately postoperatively, mean IOP lowering was clinically significant and similar following both procedures, the longer sustainable effect was observed after the second procedure (month 12: 25.5 ± 7.5 mm Hg; 12.4 ± 4.8 mm Hg; p = 0.001). No serious complications were observed. DISCUSSION/CONCLUSION: Double PreserFlo implantation appears safe and efficient for lowering IOP in glaucoma patients. Our preliminary findings suggest that double is superior to single implantation in terms of IOP lowering and the need for additional topical medication. Patients with insufficient IOP lowering following single implantation may benefit from a second implantation. Further research is warranted to evaluate double implantation as a first-line, one-stage procedure.

Nicotinamide Prevents Retinal Vascular Dropout in a Rat Model of Ocular Hypertension and Supports Ocular Blood Supply in Glaucoma Patients.

Purpose: To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma. Methods: This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA. Results: A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment. Conclusions: NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.

Short-Term Effect of Micropulse Transscleral Laser Therapy on Intraocular Pressure in Untreated Fellow Eyes of Glaucoma Patients: Preliminary Results.

It has been observed that an intraocular pressure (IOP) altering intervention in one eye is followed by a consensual response in the untreated fellow eye. The underlying mechanisms remain unclear. Involvement of neuronal, cytokine, and hormonal regulation of aqueous humor dynamics, as well as improved treatment adherence or systemic absorption of topically administered medical compounds, have been suggested. Our aim was to investigate the short-term effects of unilateral micropulse transscleral laser therapy on IOP in the fellow eye. All medical records of glaucoma patients who underwent micropulse transscleral laser therapy in a tertiary referral center between May 2019 and February 2023 were collected and analyzed. We found a significant reduction in IOP in the treated eyes, indicating successful treatment. In the fellow eyes, despite not having changed any of the pharmacological IOP-reducing therapies, a significant reduction in IOP from 17.0 ± 5.1 mmHg to 13.5 ± 4.4 mmHg (p < 0.01) was observed. This reduction was, however, short-term and reached statistical significance on the first postoperative day only. Our findings support the concept of consensual inter-eye responses to unilateral IOP changes. Further research is warranted to elucidate the mechanisms underlying this phenomenon.

Volume-rendered optical coherence tomography angiography during ocular interventions: Advocating for noninvasive intraoperative retinal perfusion monitoring.

We aimed to test for feasibility of volume-rendered optical coherence tomography angiography (OCTA) as a novel method for assessing/quantifying retinal vasculature during ocular procedures and to explore the potential for intraoperative use. Thirty patients undergoing periocular anaesthesia were enrolled, since published evidence suggests a reduction in ocular blood flow. Retinal perfusion was monitored based on planar OCTA image-derived data provided by a standard quantification algorithm and postprocessed/volume-rendered OCTA data using a custom software script. Overall, imaging procedures were successful, yet imaging artifacts occurred frequently. In interventional eyes, perfusion parameters decreased during anaesthesia. Planar image-derived and volume rendering-derived parameters were correlated. No correlation was found between perfusion parameters and a motion artifact score developed for this study, yet all perfusion parameters correlated with signal strength as displayed by the device. Concluding, volume-rendered OCTA allows for noninvasive three-dimensional retinal vasculature assessment/quantification in challenging surgical settings and appears generally feasible for intraoperative use.

Evaluation of Bicanalicular Nasolacrimal Duct Intubation as an Adjunct in Surgical Ectropion Correction.

Background and Objectives: We aimed to analyze and compare the outcomes of conventional ectropion surgery procedures with and without concurrent bicanalicular nasolacrimal duct intubation to identify if the combination of procedures could serve as a novel surgical approach to treat lower eyelid ectropion. Materials and Methods: A retrospective review of all patients who underwent surgical correction for lower eyelid ectropion at the Cantonal Hospital of Aarau between January 2019 and December 2020 was performed. Patient medical records were examined for etiology, surgical correction technique and intra- and postoperative complications. The postoperative punctal position, the pre- and postoperative epiphora and reoperation rate were also documented. Two study groups consisting of cases with isolated and combined procedures were compared, with respect to postoperative punctual and lower lid position. Results: A total of 53 lower eyelids (35 patients) were included in this study. Six months postoperatively, the correct punctum position (p = 0.1188) and improvement of epiphora (p = 0.7739) did not significantly differ between the two groups. More complications were seen in the nasolacrimal duct intubation group (p = 0.0041), which consisted of cheese wiring and one tube dislocation. Conclusion: In our study, bicanalicular nasolacrimal intubation during ectropion surgery does not seem to improve the outcome of ectropion surgery and is, therefore, not recommended on a routine basis.

Valproic Acid Reduces Neuroinflammation to Provide Retinal Ganglion Cell Neuroprotection in the Retina Axotomy Model.

Neuroinflammation is a critical and targetable pathogenic component of neurodegenerative diseases, including glaucoma, the leading cause of irreversible blindness. Valproic acid has previously been demonstrated to reduce neuroinflammation and is neuroprotective in a number of experimental settings. To determine whether valproic acid can limit retinal neuroinflammation and protect retinal neurons we used an ex vivo retina explant (axotomy) model to isolate resident glial responses from blood-derived monocytes. Neuroinflammatory status was defined using high resolution confocal imaging with 3D morphological reconstruction and cytokine protein arrays. Valproic acid significantly reduced microglia and astrocyte morphological changes, consistent with a reduction in pro-inflammatory phenotypes. Cytokine profiling demonstrated that valproic acid significantly attenuated or prevented expression of pro-inflammatory cytokines in injured retina. This identifies that the retinal explant model as a useful tool to explore resident neuroinflammation in a rapid timescale whilst maintaining a complex system of cell interactions and valproic acid as a useful drug to further explore anti-neuroinflammatory strategies in retinal disease.

Assessment of Orbital Compartment Pressure: A Comprehensive Review.

The orbit is a closed compartment defined by the orbital bones and the orbital septum. Some diseases of the orbit and the optic nerve are associated with an increased orbital compartment pressure (OCP), e.g., retrobulbar hemorrhage or thyroid eye disease. Our aim was to review the literature on the different approaches to assess OCP. Historically, an assessment of the tissue resistance provoked by the retropulsion of the eye bulb was the method of choice for estimating OCP, either by digital palpation or with specifically designed devices. We found a total of 20 articles reporting direct OCP measurement in animals, cadavers and humans. In nine studies, OCP was directly measured in humans, of which five used a minimally invasive approach. Two groups used experimental/custom devices, whilst the others applied commercially available devices commonly used for monitoring the compartment syndromes of the limbs. None of the nine articles on direct OCP measurements in humans reported complications. Today, OCP is mainly estimated using clinical findings considered surrogates, e.g., elevated intraocular pressure or proptosis. These diagnostic markers appear to reliably indicate elevated OCP. However, particularly minimally invasive approaches show promises for direct OCP measurements. In the future, more sophisticated, specifically designed equipment might allow for even better and safer measurements and hence facilitate the diagnosis and monitoring of orbital diseases.

Comparative Assessment of Retinal Blood Flow Velocity Changes Following Brimonidine and Brinzolamide Administration Using Retinal Function Imaging.

PURPOSE: Impaired ocular blood flow has been associated with the etiopathogenesis of glaucoma. Topical brimonidine lowers intraocular pressure, a major glaucoma risk factor. However, brimonidine's influence on retinal blood flow remains to be fully elucidated. Our aim was to compare the effect of topical brimonidine and brinzolamide administration on retinal blood flow velocity in second and third order vessels in healthy adults using the retinal function imager. METHODS: In 10 healthy probands between 23 and 32 years of age, one eye was randomly selected to receive 2 treatment rounds with 3 single doses of brimonidine 2 mg/mL and brinzolamide 10 mg/mL at 12-hour intervals each. The fellow eyes served as intra-individual controls. Immediately before the first drop and 2 hours after the last drop of each treatment round, all subjects were examined, including Goldmann tonometry, Pascal tonometry, assessment of retinal blood flow velocity using the retinal function imager, as well as blood pressure and pulse measurements. RESULTS: Intraocular pressure decreased significantly in treated eyes while remaining stable in control eyes, indicating reliable application of brimonidine and brinzolamide drops. In contrast, retinal blood flow velocities did not demonstrate any significant differences between groups after both treatment rounds. CONCLUSIONS: Neither brimonidine nor brinzolamide appear to alter retinal blood flow velocity in a clinically relevant manner. The slight velocity changes detected in our study are likely physiologic fluctuations. Our findings do not support the rationale of a detrimental effect of topical brimonidine on ocular blood flow and hence brimonidine may be further administered for lowering intraocular pressure with the appropriate caution. However, our study is strongly limited by the small sample size and, thus, further research with larger cohorts of healthy volunteers and patients with glaucoma is needed to confirm the results. TRANSLATIONAL RELEVANCE: The study provides information about the effect of the topically administered antiglaucoma medications brimonidine and brinzolamide on the ocular blood flow and its regulation. The findings indicate that beside the lowering of IOP there is no evidence for an additional effect on the development of glaucoma.

Comparison of Glaucoma-Relevant Transcriptomic Datasets Identifies Novel Drug Targets for Retinal Ganglion Cell Neuroprotection.

Glaucoma is a leading cause of blindness and is characterized by the progressive dysfunction and irreversible death of retinal ganglion cells. We aimed to identify shared differentially expressed genes (DE genes) between different glaucoma relevant models of retinal ganglion cell injury using existing RNA-sequencing data, thereby discovering targets for neuroprotective therapies. A comparison of DE genes from publicly available transcriptomic datasets identified 12 shared DE genes. The Comparative Toxicogenomics Database (CTD) was screened for compounds targeting a significant proportion of the identified DE genes. Forty compounds were identified in the CTD that interact with >50% of these shared DE genes. We next validated this approach by testing select compounds for an effect on retinal ganglion cell survival using a mouse retinal explant model. Folic acid, genistein, SB-431542, valproic acid, and WY-14643 (pirinixic acid) were tested. Folic acid, valproic acid, and WY-14643 demonstrated significant protection against retinal ganglion cell death in this model. The increasing prevalence of open access-omics data presents a resource to discover targets for future therapeutic investigation.

Minimally invasive measurement of orbital compartment pressure and implications for orbital compartment syndrome: a pilot study.

BACKGROUND: Diagnosis of orbital compartment syndrome is mainly based on clinical findings, such as intraocular pressure and proptosis, which try to estimate the orbital compartment pressure. However, the reliability of these surrogates is unclear. Current techniques for the direct measurement of orbital compartment pressure are widely experimental and impractical in the clinical setting. Our aim was to explore the feasibility of minimally invasive needle manometry for direct measurement of orbital compartment pressure under reproducible conditions in an in vivo model of orbital congestion. We further sought to evaluate intraocular pressure and proptosis as indicators for elevated orbital compartment pressure. METHODS: A total of 7 ml of mepivacaine 2% solution was injected into the orbital compartment in 20 patients undergoing cataract surgery under local anesthesia. A commercially available single-use manometer device was inserted between the syringe and the injection needle to measure the orbital compartment pressure for each milliliter of intraorbital volume increment. Additionally, intraocular pressure (subgroup A; n = 10) or axial globe position (subgroup B; n = 10) were measured. RESULTS: Needle manometry allowed for rapid and continuous measurement of orbital compartment pressure. Overall mean orbital compartment pressure increased from 2.5 mmHg pre- to 12.8 mmHg post-interventionally. Both, intraocular pressure (Spearman's correlation coefficient rs = 0.637, p < 0.0001) and proptosis (rs = 0.675, p < 0.0001) correlated strongly with the orbital compartment pressure. CONCLUSIONS: Needle manometry appears to be a feasible minimally invasive instrument to directly measure orbital compartment pressure, showing promises for a more routine application in managing orbital compartment syndrome. The results further suggest that both elevated intraocular pressure and proptosis are valuable indicators for orbital compartment syndrome.

Ophthalmic Screening in Patients with Coronavirus Disease 2019: A Prospective Cohort Study.

Postmortem pathological examinations, animal studies, and anecdotal reports suggest that coronavirus disease 2019 (COVID-19) could potentially affect intraocular tissue. However, published evidence is scarce and conflicting. In our study, we screened 100 eyes of 50 patients hospitalized for COVID-19. Relevant medical and ophthalmological history was assessed as well as symptoms, laboratory results, specific treatments, clinical course, and outcome. Ophthalmic exams including assessment of best corrected visual acuity (BCVA), intraocular pressure (IOP), color perception, ocular motility, ophthalmoscopy as well as optical coherence tomography (OCT) of the macula and the optic disc was performed at hospital admission and 29 to 192 days later. Of the 50 patients included, 14 (28%) were female. Median age was 64.5 (range 29-90) years. COVID-19 severity was mild in 15 (30%), severe in 30 (60%), and critical in five cases (10%). At baseline, median BCVA was 0.1 (0-1.8) Logarithm of the Minimum Angle of Resolution (LogMAR) and median IOP was 16 (8-22) mmHg. At follow-up, no relevant changes in BCVA and IOP were documented. No signs of active intraocular inflammation or optic nerve affection were found and OCT findings were widely stable during the observation period. Our findings suggest that COVID-19 does not regularly affect intraocular tissue.

Woakes Syndrome: A Rare Cause of Proptosis due to Sinonasal Polyposis.

The authors report 2 consecutive adult male patients, aged 61 and 38 years, who presented with painless unilateral proptosis. Their past medical histories were negative for asthma, allergies, and Graves disease. On examination, the nose bridge of the eldest patient was clearly enlarged. Computed tomography scans of the orbits and paranasal sinuses showed in both patients the same radiologic pattern of hyperdense ethmoidal opacifications and expansion of the inferomedial orbital floor. Histopathological analysis of the ethmoidal cells mucosa obtained during inferomedial decompression revealed benign sinonasal polyposis. These cases demonstrate that asymptomatic sinonasal polyposis can be a rare cause of proptosis.

Comparison of macular parameters after femtosecond laser-assisted and conventional cataract surgery in age-related macular degeneration.

PURPOSE: To evaluate differences in postoperative central macular thickness, central macular volume, corrected distance visual acuity (CDVA), and number of intravitreal anti-vascular endothelial growth factor (VEGF) injections between conventional and femtosecond laser-assisted cataract surgery in wet age-related macular degeneration (AMD). SETTING: Tertiary referral center, Lucerne, Switzerland. DESIGN: Retrospective case series. METHODS: Consecutive patients with AMD and cataract were enrolled between January 2010 and December 2015. Associations between postoperative changes in central macular thickness, central macular volume, CDVA, and number of anti-VEGF injections with type of surgery were assessed statistically. RESULTS: The study comprised 140 eyes (110 patients). No differences in postoperative central macular thickness (-9.20 µm; 95% confidence interval [CI], -41.68 to 23.28; P = .576), central macular volume (-0.08 mm2; 95% CI, -0.36 to 0.19; P = .553), visual acuity (0.03 logarithm of the minimum angle of resolution; 95% CI, -0.09 to 0.15; P = .647) or postoperative number of anti-VEGF injections (0.30; 95% CI, -0.45 to 1.05; P = .427) were found between the femtosecond laser group and the conventional group over a mean follow-up of 619 days ± 473 (SD). In the 33 eyes that had optical coherence tomography measurement within a postoperative period of 2 weeks, the central macular volume was significantly lower in femtosecond laser-treated eyes (-0.71 mm2; 95% CI, -1.19 to -0.23; P = .005). CONCLUSIONS: Overall, the postoperative course between wet AMD after femtosecond laser and conventional cataract surgery was equal. During the early follow-up, femtosecond laser-treated eyes had less subclinical macular edema, indicating a possible benefit for patients with macular vulnerability.