Corneal Microaneurysm-A Vascular Feature of Conjunctival Squamous Intraepithelial Neoplasia.

PURPOSE: The diagnosis of conjunctival squamous intraepithelial neoplasia (CSIN) can be difficult because of the heterogeneous appearance. Despite established risk factors and diagnostic support by high-resolution optical coherence tomography (hrOCT) and indocyanine green angiography (ICGA), the only reliable diagnostic method is a histological work-up. This case report is the first to describe corneal microaneurysms in CSIN as a vascular feature for conjunctival tumor angiogenesis. METHODS: An 84-year-old male patient was referred with a suspected diagnosis of pterygium. Biomicroscopic examination revealed a whitish epithelial lesion of conjunctival origin with centripetal corneal growth and extension over 5 limbal hours. Intralesional vascularization showed highly altered morphology with aneurysmal changes. After imaging with hrOCT and ICGA, excision was performed in a "no-touch double-freeze and thaw" technique, followed by histological and immunohistochemical work-up. RESULTS: hrOCT showed an epithelial, hyperreflective lesion with a maximum thickness of 272 µm and sharp central border. ICGA confirmed active perfusion and partial thrombosis of the aneurysmal terminal vascular buds dilated to 405 µm with early dye leakage within the first minute. Histological examination confirmed the clinical diagnosis of CSIN with focal high-grade dysplasia. Postoperatively, there was no recurrence during the observation period of 5 months. CONCLUSIONS: Intralesional terminal microaneurysms are a feature of tumor angiogenesis in CSIN. The relevance and frequency of this potential new risk factor for malignancy should be investigated in further studies.

Artificial Intelligence (AI) Reveals Ethnic Disparities in Cataract Detection and Treatment.

INTRODUCTION: The aim of this work is to identify patients at risk of limited access to healthcare through artificial intelligence using a name-ethnicity classifier (NEC) analyzing the clinical stage of cataract at diagnosis and preoperative visual acuity. METHODS: This retrospective, cross-sectional study includes patients seen in the cataract clinic of a tertiary care hospital between September 2017 and February 2020 with subsequent cataract surgery in at least one eye. We analyzed 4971 patients and 8542 eyes undergoing surgery. RESULTS: The NEC identified 360 patients with names classified as 'non-German' compared to 4611 classified as 'German'. Advanced cataract (7 vs. 5%; p = 0.025) was significantly associated with group 'non-German'. Mean best-corrected visual acuity in group 'non-German' was 0.464 ± 0.406 (LogMAR), and in group 'German' was 0.420 ± 0.334 (p = 0.009). This difference remained significant after exclusion of patients with non-lenticular ocular comorbidities. Surgical time and intraoperative complications did not differ between the groups. Retrobulbar or general anesthesia was chosen significantly more frequently over topical anesthesia in group 'non-German' compared to group 'German' (24 vs. 18% respectively; p < 0.001). CONCLUSIONS: This study shows that artificial intelligence is able to uncover health disparities between people with German compared to non-German names using NECs. Patients with non-German names, possibly facing various social barriers to healthcare access such as language barriers, have more advanced cataracts and worse visual acuity upon presentation. Artificial intelligence may prove useful for healthcare providers to discover and counteract such inequalities and establish tailored preventive measures to decrease morbidity in vulnerable population subgroups.

Transforming Tele-Ophthalmology: Utilizing Cloud Computing for Remote Eye Care.

BACKGROUND: Tele-ophthalmology is gaining recognition for its role in improving eye care accessibility via cloud-based solutions. The Google Cloud Platform (GCP) Healthcare API enables secure and efficient management of medical image data such as high-resolution ophthalmic images. OBJECTIVES: This study investigates cloud-based solutions' effectiveness in tele-ophthalmology, with a focus on GCP's role in data management, annotation, and integration for a novel imaging device. METHODS: Leveraging the Integrating the Healthcare Enterprise (IHE) Eye Care profile, the cloud platform was utilized as a PACS and integrated with the Open Health Imaging Foundation (OHIF) Viewer for image display and annotation capabilities for ophthalmic images. RESULTS: The setup of a GCP DICOM storage and the OHIF Viewer facilitated remote image data analytics. Prolonged loading times and relatively large individual image file sizes indicated system challenges. CONCLUSION: Cloud platforms have the potential to ease distributed data analytics, as needed for efficient tele-ophthalmology scenarios in research and clinical practice, by providing scalable and secure image management solutions.

Ocular phenotype and therapeutic interventions in keratitis-ichthyosis-deafness (KID) syndrome.

BACKGROUND: To report ocular manifestations, clinical course, and therapeutic management of patients with molecular genetically confirmed keratitis-ichthyosis-deafness syndrome. METHODS: Four patients, aged 19 to 46, with keratitis-ichthyosis-deafness syndrome from across the UK were recruited for a general and ocular examination and GJB2 (Cx26) mutational analysis. The ocular examination included best-corrected visual acuity, slit-lamp bio-microscopy, and ocular surface assessment. Mutational analysis of the coding region of GJB2 (Cx26) was performed by bidirectional Sanger sequencing. RESULTS: All four individuals had the characteristic systemic features of keratitis-ichthyosis-deafness syndrome. Each patient was found to have a missense mutation, resulting in the substitution of aspartic acid with asparagine at codon 50 (p.D50N). Main ophthalmic features were vascularizing keratopathy, ocular surface disease, hyperkeratotic lid lesions, recurrent epithelial defects, and corneal stromal scarring. One patient had multiple surgical procedures, including superficial keratectomies and lamellar keratoplasty, which failed to prevent severe visual loss. In contrast, oral therapy with ketoconazole stabilized the corneal and skin disease in two other patients with keratitis-ichthyosis-deafness syndrome. The patient who underwent intracorneal bevacizumab injection showed a marked reduction in corneal vascularization following a single application. CONCLUSIONS: Keratitis-ichthyosis-deafness syndrome is a rare ectodermal dysplasia caused by heterozygous mutations in GJB2 (Cx26) with a severe, progressive vascularizing keratopathy. Oral ketoconazole therapy may offer benefit in stabilizing the corneal and skin disease.

Integrating a Novel Eye Imaging System into Clinical Practice: An Open-Source DICOM Simulation Platform.

BACKGROUND: The integration of innovative imaging technologies into clinical workflows requires the utilization of a standardized data exchange format. The "Digital Imaging and Communications in Medicine" (DICOM) standard is widely used in healthcare to process and transfer medical images. However, no simulation environment is ready to use for development. The objective of this paper is to provide an open-source DICOM platform for integrating a novel ocular photography system into a clinical setting. METHODS: After a thorough analysis of the available open-source tools, a subset was selected and aligned with the U-Eyecare Profile of Integrating the Healthcare Enterprise (IHE). RESULTS: Orthanc served as a PACS with a modality worklist and the OHIF-Viewer for image retrieval. Minimal interfaces for the electronic health record and image modality were created. Docker-compose further integrates all components and simulates the network protocols DICOM Message Service Element and DICOMWeb. DISCUSSION: The platform was used to develop and integrate the developed image modality and will be further utilized for teleophthalmology and processing eye images. The platform could be useful for other researchers to integrate an image modality into a clinical environment along IHE.

Data Exchange Standards in Teleophthalmology: Current and Future Developments.

BACKGROUND: Teleophthalmology services are considered capable of supporting screening, early diagnosis, and monitoring of leading causes of blindness on a global scale. Therefore, standards and best practices are needed to seamlessly exchange medical ocular images and related data among relevant stakeholders with maximum interoperability. OBJECTIVES: This paper provides an overview of current standards in the field of store-and-forward teleophthalmology data exchange and further developments in this area. METHODS: A literature review was conducted for healthcare standards with a focus on data exchange in ophthalmology. RESULTS: IHE, HL7 FHIR, DICOM, and clinical terminologies are considered the most important standards, providing distinct concepts, solutions, and guidelines for ophthalmology. CONCLUSION: Available standards provide the necessary base for teleophthalmology on technical and semantic interoperability, but practical use is limited due to missing process interoperability resulting in proprietary interfaces of vendors and rejection by ophthalmologists. Further investigations should analyze processual needs on ophthalmology data exchange standards.

Eye bank versus surgeon prepared Descemet stripping automated endothelial keratoplasty tissues: Influence on adhesion force in a pilot study.

PURPOSE: To evaluate and compare the biomechanical properties of the eye bank-prepared and surgeon prepared Descemet stripping automated endothelial keratoplasty (DSAEK) tissues. METHODS: In this laboratory study, corneal tissues for research were randomly allocated in the following groups: a) surgeon-cut DSAEK and b) eye bank-prepared (pre-cut and pre-loaded) DSAEK. Endothelial cell loss (ECL), immunostaining for tight junction protein ZO-1, elastic modulus, and adhesion force were investigated. RESULTS: ECL was not found to be significantly different between surgeon-cut DSAEK (7.8% ±6.5%), pre-cut DSAEK (8.6% ±2.3%), and pre-loaded DSAEK (11.1% ±4.8%) (P = 0.5910). ZO-1 was expressed equally across all groups. Surgeon-cut DSAEK grafts showed a significantly higher elastic modulus compared to pre-cut and pre-loaded DSAEK groups (P = 0.0047 and P < 0.0001, respectively). Adhesion force was significantly greater in the surgeon-cut DSAEK compared to pre-cut (P < 0.0001) or pre-loaded DSAEK groups (P = 0.0101). CONCLUSION: The laboratory data on the biomechanics of DSAEK grafts suggests that surgeon-cut DSAEK grafts present higher elastic modulus and adhesion force compared to eye bank-prepared DSAEK grafts.

Eye bank versus surgeon prepared DMEK tissues: influence on adhesion and re-bubbling rate.

AIM: To investigate the difference in adhesion and rebubbling rate between eye bank and surgeon prepared Descemet membrane endothelial keratoplasty (DMEK) tissues. METHODS: Laboratory and clinical retrospective comparative interventional case series. Research corneal tissues were obtained for laboratory investigation. The clinical study involved patients with endothelial dysfunction who underwent DMEK surgery and tamponade with air. Tissues were stripped using a standard DMEK stripping technique (SCUBA) and shipped as prestripped or loaded in a 2.2 intra-ocular lens cartridge with endothelium facing inwards (preloaded) before transporting from the eye bank to the surgeon. For surgeon prepared tissues, all the grafts were stripped in the theatre and transplanted or stripped in the laboratory and tested immediately. Adhesion force and elastic modulus were measured in the centre and mid-periphery in a laboratory ex vivo investigation using atomic force microscopy, while rebubbling rates were recorded in the clinical study. RESULTS: There was no difference in endothelial cell viability between surgeon or eye bank prepared tissue. Surgeon-stripped DMEK grafts in the laboratory investigation showed significantly higher elastic modulus and adhesion force compared to prestripped and preloaded tissues (p<0.0001). In the clinical data, rebubbling rates of 48%, 40% and 15% were observed in preloaded, prestripped and surgeon-stripped DMEK grafts, respectively. Rebubbling rates were significantly associated with combined cataract surgery (p=0.009) and with time from harvesting the graft to the surgery (p=0.02). CONCLUSIONS: Decreased adhesion forces and elastic modulus in eye bank prepared tissues may contribute to increased rebubbling rates.

Imaging of vascular abnormalities in ocular surface disease.

The vascular system of the ocular surface plays a central role in infectious, autoimmune, inflammatory, traumatic and neoplastic diseases. The development, application, and monitoring of treatments for vascular abnormalities depends on the in vivo analysis of the ocular surface vasculature. Until recently, ocular surface vascular imaging was confined to biomicroscopic and color photographic assessment, both limited by poor reproducibility and the inability to image lymphatic vasculature in vivo. The evolvement and clinical implementation of innovative imaging modalities including confocal microscopy, intravenous, and optical coherence tomography-based angiography now allows standardized quantitative and functional vascular assessment with potential applicability to automated analysis algorithms and diagnostics.

Assessment of the correlation of the tear breakup time with quality of vision and dry eye symptoms after SMILE surgery.

PURPOSE: It is well reported that dry eye symptoms can increase after many refractive surgery procedures. This study aims to provide a clinical understanding of the correlation of fluorescein tear film breakup time (FTBUT) with quality of vision (QoV) and dry eye symptoms following small incision lenticule extraction surgery (SMILE). METHODS: Patients electing to have SMILE surgery were subdivided into 2 groups: Group 1 included short preoperative FTBUTs of 3 to 6 seconds (s); Group 2 included long FTBUTs of ≥ 8 s. Uncorrected distance visual acuity, corrected distance visual acuity, manifest refraction, FTBUT, QoV and Ocular Surface Disease Index (OSDI) questionnaires were recorded 1 and 6 months postoperatively. RESULTS: Thirty-nine subjects were included in each group. There was no significant difference in visual outcomes between the 2 groups at both the 1- and 6-month postoperative assessments. FTBUT remained significantly lower in group 1. Oxford staining was initially higher for group 1 at 1 month (P = 0.007), but there was no significant difference at 6 months (P = 0.180). There was no significant difference in QoV or OSDI scores between the 2 groups at both postoperative visits. CONCLUSIONS: Low preoperative FTBUT (3-6 s) does not appear to negatively affect postoperative visual outcomes or results in a greater likelihood of dry eye symptoms and poor ocular surface compared to eyes with a longer preoperative FTBUT. These results suggest that a low preoperative FTBUT does not necessarily increase the likelihood of poor visual acuity, dry eyes symptoms, or poor ocular surface outcomes following SMILE surgery.

Effects of COVID-19 protective measures on the ophthalmological patient examination with an emphasis on gender-specific differences.

OBJECTIVE: In response to the COVID-19 pandemic, strict hygiene and containment measures have been instituted in the clinical ophthalmological examination to prevent virus transmission. The aim of this study is to assess the effects of these protective measures on the quality of the examination with an emphasis on gender-specific differences. METHODS AND ANALYSIS: An online survey was sent to ophthalmologists in 10 countries. The collected data included demographics, place of work, current professional status, COVID-19 protective measures and their impact on the quality of the examination. Descriptive statistics were used to analyse the data. Fisher's exact test was used to analyse gender differences. RESULTS: A total of 120 responses were collected. 54.0% of the respondents identified as female and 43.4% as male. Over 75% agreed that protective measures made the examination conditions more difficult. The major problems were fogging of the lenses (87.6%) or slit lamp oculars (69.9%), reduced operability of the slit lamp due to protective barriers (60.2%) and time delay due to disinfection measures (68.1%). Significantly more women than men reported that they used filtering face piece (FFP2) instead of surgical masks (p=0.02). More male participants reported that they removed their mask to prevent fogging (p=0.01). 31% of all participants felt that the COVID-19 protective measures reduced the overall quality of slit lamp examination and 43.4% reported a reduced quality of fundoscopic examination. CONCLUSION: COVID-19 related safety measures reduce the feasibility of the clinical ophthalmological examination. Practicable solutions are required to maintain good examination quality without compromising personal safety.

Ocular surface angiography: from neovessels to neoplasia.

The ocular surface vascular system plays a key role in corneal and conjunctival inflammatory, infectious and neoplastic pathology. Angiographic vessel analysis using intravenous dyes and optical coherence tomography technology allow both the quantitative and functional assessment of conjunctival vasculature and corneal neovessels. Based on a thorough understanding of vascular alterations in ocular surface disease, angiographic assessment facilitates the clinical management of corneal neovascularisation, the grading of ocular surface inflammation and the identification of tumour angiogenesis in dysplastic or malignant lesions. This review summarises key aspects of the clinical application of corneal and conjunctival angiography as presented at the 2021 virtual Bowman Club meeting.

Tips, Tricks, and Guides in Descemet Membrane Endothelial Keratoplasty Learning Curve.

Lamellar keratoplasty is fast becoming the most popular form of corneal transplantation. The adoption of Descemet membrane endothelial keratoplasty (DMEK) in the management of Fuchs endothelial dystrophy and pseudophakic bullous keratopathy is partly responsible for this shift in the paradigm of management of corneal pathology. The learning curve of DMEK, however, has been proven to be much steeper than previous endothelial keratoplasty procedures. To ease the procedure, experts have proposed multiple innovative techniques from tissue preparation to graft unfolding to aid the more novice surgeon. Here, we collate and share tips and tricks from our collective experiences to support the learning curve and outcomes in DMEK for both the novice and more experienced corneal transplant surgeons.

Indocyanine Green Angiographic Assessment of Conjunctival Melanocytic Disorders.

PURPOSE: To investigate whether transvascular indocyanine green (ICG) dye leakage is associated with conjunctival malignancy. METHODS: This is a prospective interventional study. Patients presenting with circumscribed conjunctival melanocytic disorders (CMDs) were included and examined using color photography, anterior segment optical coherence tomography to measure lesion size, and fluorescein and ICG angiography to measure vascular pattern and leakage. Time to vascular leakage was measured by 2 independent observers. Lesions were characterized as benign or malignant based on histopathological features. RESULTS: Thirty patients with CMD were included: 22 lesions were benign (conjunctival nevus, n = 20; conjunctival melanocytic intraepithelial neoplasia without atypia, n = 2) and 8 were malignant (in situ conjunctival melanoma n = 2; invasive conjunctival melanoma, n = 6). Malignant lesions had larger mean maximal diameters (11.0 ± 4.5 vs. 4.2 ± 2.5 mm, P = 0.003) and more frequently showed intrinsic tumor vasculature (8 of 8 vs. 10 of 22, P = 0.007). The mean time to ICG leakage was 350.9 ± 165.9 seconds in benign and 59.6 ± 22.1 seconds (P = 0.002) in malignant lesions and was inversely correlated with lesion size and thickness. CONCLUSIONS: Time to angiographic ICG dye leakage is significantly shorter in malignant versus benign CMD.

Observation of angiographic dye leakage in ocular surface squamous neoplasia.

PURPOSE: The clinical diagnosis of ocular surface squamous neoplasia is challenging, mostly requiring excisional biopsy. Human tumor angiogenesis is characterized by abnormal vessel architecture and transvascular hyperpermeability. This case report describes features of fluorescein and indocyanine green angiography in a case of conjunctival intraepithelial neoplasia. OBSERVATIONS: Color photography, optical coherence tomography, fluorescein and indocyanine green angiography were performed in a patient with suspected conjunctival intraepithelial neoplasia before excisional biopsy and histologic confirmation of clinical diagnosis. Fluorescein dye showed extensive early extravascular dye leakage within the limits of the lesion. Indocyanine green dye displayed corneal terminal vessel bulbs with early leakage after 70 seconds and showed diffuse intralesional dye leakage after 7 minutes. CONCLUSIONS: Increased fluorescein and early indocyanine green dye leakage can be used to confirm active angiogenesis already in early stages of dysplastic ocular surface squamous neoplasia. Late leakage of indocyanine green dye may be due to chronic transvascular hyperpermeability within intrinsic tumor vessels. The leakage behaviour of intravenous dyes has the potential to serve as a diagnostic indicator of active growth in dysplastic ocular surface neoplastic lesions.

En-face analysis of the human limbal lymphatic vasculature.

PURPOSE: To describe the location and morphometric characteristics of the human limbal lymphatic vasculature and its relation to the marginal corneal vascular arcades (MCA). METHODS: Ex vivo confocal microscopic (CM) imaging and immunofluorescence double staining for CD-31 and D2-40 of histological en-face sections using 12 preserved human cadaveric corneoscleral discs were performed, followed by a semi-automated morphometric analysis of the two-dimensional vascular network architecture. RESULTS: Ex vivo CM confirmed the presence of 2 distinct vascular networks. The haematic limbal vascular complex (HLVC) extended further into the cornea, forming typical MCAs. The lymphatic limbal vascular complex (LLVC) was peripheral from the termination of Bowman's layer and was also found to be peripheral to and deeper than the HLVC. LLVC and HLVC were significantly different with respect to vessel diameter, segment length and wall thickness. CONCLUSION: The lymphatic vasculature of the human corneoscleral limbal region displays specific morphometric features that allow its differentiation from haematic vessels using CM.

Horsepower of Doctors' Cars Correlates with Cardiovascular Risk and Sedentary Lifestyle but Not with Sexual Dysfunction or Sexual Satisfaction.

Background: The horsepower not only of doctors' cars correlates with personal income and social status. However, no clear relationship has previously been described between the horsepower of doctors' cars and cardiovascular health or sexual dysfunction and/or satisfaction. Objective: Cross-sectional online survey to evaluate associations between self-reported horsepower of physicians' cars and health aspects. Methods: Of 1877 physicians from the two University-Hospitals in Austria that were asked to participate in the study, 363 (37.7 ± 8.0 years, 208 (57.3%) men) were included into the final analysis. Results: Physicians that own a car with a stronger engine were significantly older, were more often male, had more often a leading position, had a higher monthly income (all p < 0.001), had a higher scientific output (p = 0.030), and had hypercholesteremia more often (p = 0.009). They also tended to have a higher body mass index (p = 0.088), reported a higher maximum weight in previous years (p = 0.004) and less often reported regular healthy commuting to and from work (p = 0.010). No significant associations were found for self-reported physical fitness, smoking status, and arterial hypertension. In addition, sexual satisfaction and sexual dysfunction were also not related to horsepower in the whole population and the male subgroup. The findings essentially persisted after controlling for age. Conclusion: The horsepower of Austrian physicians' cars correlates with senior position and increased cardiovascular risk. However, our data shows no relationship between sexual dysfunction or lack of sexual satisfaction and the horsepower of doctors' cars.

Detecting Change in Conjunctival Hyperemia Using a Pixel Densitometry Index.

PURPOSE: To investigate a pixel densitometry index (PDI) for measuring ocular surface inflammation (OSI). METHODS: Efron's grading was performed by two independent observers. Color photographs and indocyanine green angiography were undertaken before and after instillation of phenylephrine (PE) hydrochloride 2.5%. RESULTS: A total of 15 patients with and 10 without OSI were included. PDI before and after PE was 73.29 ± 30.71 and 50.87 ± 17.46 (p = 0.036) in patients with inflammation and 52.86 ± 16.90 and 39.63 ± 12.04 (p = 0.0024) in those without OSI. The reduction in Efron grades following PE was 25% (mean 0.46 ± 0.50, median 0.50; p < 0.01). The coefficient of variation pre- and post-PE was lower using the PDI (42% and 50%) than with the Efron grades (59% and 72%). CONCLUSION: The PDI allows the objective detection of change in conjunctival hyperemia with potential direct applicability to noninvasive angiography such as optical coherence tomography-based angiography.

Cross-Country Transportation Efficacy and Clinical Outcomes of Preloaded Large-Diameter Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty Grafts.

PURPOSE: To evaluate the clinical outcomes of preloaded large-diameter ultra-thin grafts for Descemet stripping automated endothelial keratoplasty (UT-DSAEK) after cross-country shipment. METHODS: A laboratory study in an eye bank and a clinical cohort study in an academic tertiary care center were performed. UT-DSAEK (9.5 mm diameter) grafts (n = 7) were prepared, loaded into a commercial device (iGlide; Eurobio, Les Ulis, France), preserved for 4 days at room temperature in transport medium, and analyzed. In a retrospective study, preloaded tissues (n = 39) for clinical use were prepared, transported from Italy to the United Kingdom, and surgically delivered into the eyes of patients undergoing UT-DSAEK. Central and peripheral endothelial cell density (ECD) and viability were measured before and after loading and storage of the grafts in the laboratory study. Clinically, best-corrected visual acuity, ECD before and at final follow-up, dislocation rate, primary graft failure, and surgical time were recorded. RESULTS: In the laboratory study, postcut central graft thickness was 93.3 ± 17.2 µm. ECD and cell mortality did not change significantly before and after preservation (P = 0.8). Cell loss after 4 days of preservation was 1.7% ± 1.6%. Clinically, 39 eyes of 39 patients at final follow-up showed a mean central graft thickness of 88 ± 22 µm and a best-corrected visual acuity of 0.34 ± 0.24 logMAR. Nine of 39 cases (23%) needed rebubbling, and 28% cell loss was observed at final follow-up. CONCLUSIONS: Large-diameter UT-DSAEK grafts can be prepared and preloaded in the eye bank using the iGlide and transported to the surgical center facilitating surgery for patients undergoing UT-DSAEK, potentially reducing tissue wastage, surgical time, and costs related to surgery.