Novel Application of Conjunctival Anterior Segment Optical Coherence Tomography Angiography to Assess Ocular Redness.

PURPOSE: The aim of this study was to determine anterior segment optical coherence tomography angiography (AS-OCTA) parameters to assess ocular redness severity. METHODS: AS-OCTA analyses of 60 eyes of 40 patients were grouped according to ocular redness stages using the 5-category validated bulbar redness scale in a cross-sectional retrospective study (groups 1-5). A subset of patients with slit-lamp photographs, total 35 eyes of 23 patients, were assessed with 10-category validated bulbar redness scale for comparison. AS-OCTA images of nasal and temporal bulbar conjunctiva were analyzed. Vessel density (VD) represented the blood flow pixels by the total pixels of image (%); vessel diameter index represented the VD by the skeletonized density; fractal dimension, measured with the box-count method, represented the vessel branching complexity. Averaged nasal and temporal parameters for each eye were correlated to validated bulbar redness scales. RESULTS: There was no statistical difference between groups for age ( P = 0.118), sex ( P = 0.501), eye laterality (OD/OS; P = 0.111), or location (nasal/temporal; P = 0.932). In the 5-category scale, VD significantly increased from group 1 to 2 (31.5 ± 1.9% and 33.4 ± 2.2%, P = 0.023), 2 to 3 (36.0 ± 3.5%, P < 0.001), and 4 to 5 (40.2 ± 2.9 and 46.5 ± 2.8, P < 0.001). The correlations were 0.805 ( P < 0.001) and 0.893 ( P < 0.001) for the 5-category and 10-category scales, respectively. Vessel diameter index showed a significant increase from 1 to 2 (2.90 ± 0.17 and 3.00 ± 0.15; P = 0.004) and 4 to 5 (2.92 ± 0.31 and 3.33 ± 0.08; P = 0.001). The correlations were 0.550 ( P < 0.001) and 0.625 ( P < 0.001) for the respective scales. The fractal dimension showed no significant differences between subsequent groups. The correlations were 0.445 ( P < 0.001) and 0.583 ( P < 0.001), respectively. CONCLUSIONS: Conjunctival AS-OCTA VD was the most reliable parameter to assess ocular redness.

A novel interlamellar oral mucosa graft surgery technique using fibrin glue for the treatment of trichiasis / Nova técnica cirúrgica de enxerto interlamelar de mucosa oral usando cola de fibrina para o tratamento de triquíase

ABSTRACT Purpose: The purpose of this study was to evaluate the long-term outcomes of patients with trichiasis treated with a modified interlamellar oral mucosa graft surgery technique using fibrin glue. Methods: A prospective study was conducted at the Oculoplastic Department of Ouro Verde Hospital Complex. Patients with recurrent trichiasis without entropion who did not respond to conventional therapy, underwent intermarginal lamellar splitting of the eyelid and oral mucous graft insertion with fibrin glue replacing sutures. They were then evaluated at 1-day, 1-week, 1-month, 6-month, and 4-year follow-ups. Graft adherence, symptom resolution, esthetic satisfaction, overall patient satisfaction, and trichiasis recurrence were assessed at 6-month and 4-year follow-ups. Results: Fifteen patients (a total of 19 eyes) were included, of whom 10 (66.7%) were female and 5 (33.3%) were male. The mean age was 75.4 ± 10.5 years (range, 54-98 years). Acquired trichiasis was the main cause. Of the patients with acquired trichiasis, 12 (86.7%) had chronic blepharitis, 2 (13.3%) had an undetermined cause, and one (6.7%) had trachomatous trichiasis. Most cases involved only one eyelid segment (89.4%) and =5 lashes (84.2%; minor trichiasis). No adverse reactions from the fibrin glue were reported and no sutures were required after graft placement. At 6 months, no graft failures occurred, 17 eyes of 13 patients (89.4%) showed good graft adherence, 2 eyes of 2 patients (10.5%) showed partial graft adherence, and 2 eyes of 1 patient (10.5%) had trichiasis recurrence. At 4-year follow-up, no graft failure occurred, 3 patients (3 eyes) were lost to follow-up, and 2 eyes of 2 patients (14.2%) had trichiasis recurrence. The 4-year cumulative success rate was 78.9%. Conclusions: The modified interlamellar surgery with fibrin glue showed a good long-term success rate. This technique reduces surgical time, facilitates smaller graft insertion, and therefore, should be considered for recalcitrant minor trichiasis without entropion.>

RESUMO Objetivo: O objetivo deste estudo foi avaliar os resultados a longo prazo da técnica cirúrgica modificada de enxerto interlamelar de mucosa oral usando cola de fibrina para o tratamento de triquíase. Métodos: Um estudo prospectivo foi realizado no Departamento de Óculo-plástica do Complexo Hospital Ouro Verde. Pacientes com triquíase recorrente sem entrópio, que não responderam à terapia convencional, foram submetidos à cirurgia com separação intermarginal das lamelas das pálpebras e inserção de enxerto de mucosa oral usando cola de fibrina, substituindo a sutura. Pacientes foram avaliados 1 dia, 7 dias, 1 mês, 6 meses e 4 anos após a cirurgia. A aderência do enxerto, resolução dos sintomas, satisfação estética, satisfação geral do paciente e recorrência de triquíase foram avaliados aos 6 meses e aos 4 anos. Resultados: Quinze pacientes (total de 19 olhos) foram incluídos, dos quais 10 (66.7%) eram do sexo feminino e 5 (33.3%) do sexo masculino. A média de idade foi 75.4 ± 10.5 anos (intervalo 54-98 anos). Triquíase adquirida foi a principal causa, da qual 12 pacientes apresentaram blefarite crônica (86.7%), 2 pacientes com causa indeterminada (13.3%) e 1 paciente com triquíase tracomatosa (6.7%). A maioria dos casos envolveu apenas um segmento da pálpebra (89.4%) e com =5 cílios (84.2%; triquíase menor). Nenhuma reação adversa foi reportada com o uso da cola de fibrina e nenhum caso necessitou de sutura após inserção do enxerto. Aos 6 meses, não houve nenhuma falha de enxerto, 17 olhos de 13 pacientes (89.4%) apresentaram boa aderência de enxerto, 2 olhos de 2 pacientes (10.5%) mostraram aderência parcial do enxerto e 2 olhos de 1 paciente (10.5%) apresentaram recorrência da triquíase. Aos 4 anos, não houve nenhuma falha de enxerto, 3 olhos de 3 pacientes tiveram perda de seguimento e 2 olhos de 2 pacientes (14.2%) apresentaram recorrência da triquíase. A taxa de sucesso acumulativa após 4 anos foi de 78.9%. Conclusão: A cirurgia modificada de enxerto interlamelar de mucosa oral usando cola de fibrina mostrou uma boa taxa de sucesso a longo prazo. Esta técnica reduz o tempo cirúrgico, facilita a inserção de enxertos menores e, portanto, deve ser considerada em triquíase menor sem entrópio resistente ao tratamento convencional.

A novel interlamellar oral mucosa graft surgery technique using fibrin glue for the treatment of trichiasis.

PURPOSE: The purpose of this study was to evaluate the long-term outcomes of patients with trichiasis treated with a modified interlamellar oral mucosa graft surgery technique using fibrin glue. METHODS: A prospective study was conducted at the Oculoplastic Department of Ouro Verde Hospital Complex. Patients with recurrent trichiasis without entropion who did not respond to conventional therapy, underwent intermarginal lamellar splitting of the eyelid and oral mucous graft insertion with fibrin glue replacing sutures. They were then evaluated at 1-day, 1-week, 1-month, 6-month, and 4-year follow-ups. Graft adherence, symptom resolution, esthetic satisfaction, overall patient satisfaction, and trichiasis recurrence were assessed at 6-month and 4-year follow-ups. RESULTS: Fifteen patients (a total of 19 eyes) were included, of whom 10 (66.7%) were female and 5 (33.3%) were male. The mean age was 75.4 ± 10.5 years (range, 54-98 years). Acquired trichiasis was the main cause. Of the patients with acquired trichiasis, 12 (86.7%) had chronic blepharitis, 2 (13.3%) had an undetermined cause, and one (6.7%) had trachomatous trichiasis. Most cases involved only one eyelid segment (89.4%) and =5 lashes (84.2%; minor trichiasis). No adverse reactions from the fibrin glue were reported and no sutures were required after graft placement. At 6 months, no graft failures occurred, 17 eyes of 13 patients (89.4%) showed good graft adherence, 2 eyes of 2 patients (10.5%) showed partial graft adherence, and 2 eyes of 1 patient (10.5%) had trichiasis recurrence. At 4-year follow-up, no graft failure occurred, 3 patients (3 eyes) were lost to follow-up, and 2 eyes of 2 patients (14.2%) had trichiasis recurrence. The 4-year cumulative success rate was 78.9%. CONCLUSIONS: The modified interlamellar surgery with fibrin glue showed a good long-term success rate. This technique reduces surgical time, facilitates smaller graft insertion, and therefore, should be considered for recalcitrant minor trichiasis without entropion.>.

Automated Image Threshold Method Comparison for Conjunctival Vessel Quantification on Optical Coherence Tomography Angiography.

Purpose: To determine the impact of image binarization and the best thresholding method for conjunctival optical coherence tomography angiography (OCTA). Methods: Vessel density (VD) of 14 OCTA conjunctival images (nine nasal and five temporal conjunctivas, and eight right and six left eyes) from normal subjects was analyzed. The binarization of gold-standard images, created by removing pixels that do not represent vessels on ImageJ software, was assessed by three masked graders to determine consistency of VD for images. Various thresholding methods on ImageJ, including manual, 1-, 2- and 3-step processes, were performed on unprocessed images for comparison. Interclass correlation coefficient (ICC) ≥0.750 were classified as good reliability and selected for calculation of the performance of the pixel location in the binarized images of each method. Results: Analysis of the gold-standard threshold method achieved an ICC of 0.816 with excellent agreement (R2 = 0.965, P < 0.001). From a total 28 different methods and variations performed, only nine methods performed with good reliability, including two 1-step thresholds, six 2-step thresholds, and one 3-step threshold method. Overall, 2-step threshold methods were more reliable than 3-step threshold methods. The 2-step method of Bandpass filter + Phansalkar local threshold (LT) showed the best performance with mean pixel accuracy of 86.9% ± 6.8%, area under the curve of 0.826, sensitivity of 79.0%, and specificity 86.1%. Conclusions: Bandpass filter + Phansalkar LT was the best method for VD measurement in conjunctival OCTA. Most commonly reported threshold methods showed unsatisfactory agreement. There is a need in the OCTA field for a standardized method to allow comparison between different studies. Translational Relevance: The proposed threshold method using a widely accessible and commonly used software provides an accurate VD measurement for future OCTA studies.

A Single Administration of OC-01 (Varenicline Solution) Nasal Spray Induces Short-Term Alterations in Conjunctival Goblet Cells in Patients with Dry Eye Disease.

INTRODUCTION: Dry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied. METHODS: In this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: The study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild. CONCLUSIONS: This study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03688802.

Anterior segment optical coherence tomography angiography in the assessment of ocular surface lesions.

PURPOSE: Describe the utility of anterior segment optical coherence tomography angiography (AS-OCTA) to assess ocular surface lesions. METHODS: Retrospective, case-control study of 10 eyes of 9 patients with malignant lesions and 23 eyes of 22 patients with benign lesions. Lesions included 13 epithelial, 10 pigmented and 10 lymphoid lesions. Graders performed an average of 3 depth and diameter measurements of peri-lesional vessels entering each lesion on AS-OCTA. Statistical models to assess differences between groups accounted for bilateral eye inclusion and lesion thickness (on AS-OCT). Receiver operating characteristic (ROC) curve and area under the curve (AUC) were performed for each parameter. RESULTS: In the benign and malignant groups, age was 49.5 ± 22.4 and 64.3 ± 10.6 years (p = 0.145) with 45% males and 55% males (p = 0.458), in their respective groups. AS-OCTA showed greater peri-lesional vessel depth and diameter in malignant lesions (315.2 ± 73.0 µm, p < 0.001 and 76.4 ± 18.2 µm, p < 0.001; respectively) compared to benign lesions (199.4 ± 34.1 µm and 44.0 ± 9.4 µm, respectively). Malignant lesions showed deep and dilated peri-lesional vessels, which may represent feeder vessels. Vessel depth showed AUC = 0.980, 90.9% sensitivity and 100.0% specificity with a 236.5 µm cutoff. Vessel diameter showed AUC = 0.960, 100.0% sensitivity and 88.9% specificity with a 53.9 µm cutoff. CONCLUSION: AS-OCTA shows greater peri-lesional vessel depth and diameter of malignant lesions compared to benign lesions. This imaging modality provides novel and non-invasive functional vascular parameters that can potentially aid the assessment of ocular surface lesions.

The utility of anterior segment optical coherence tomography angiography for the assessment of limbal stem cell deficiency.

PURPOSE: To determine the utility of anterior segment optical coherence tomography angiography (AS-OCTA) in assessing limbal stem cell deficiency (LSCD). METHODS: Twenty-six eyes of 24 LSCD patients, classified clinically into stage I, II and III, and 12 eyes of 12 healthy subjects were included. AS-OCTA images were analyzed by two masked observers, measuring the maximum corneal vascular extension (CoVE) from the limbus to the furthest vessel over the cornea, and corneal vascular thickness (CoVT) from the most superficial to the deepest corneal vessel. RESULTS: CoVE was 0.27 ± 0.10, 0.79 ± 0.21, 1.68 ± 0.89 and 2.53 ± 0.82 mm in controls, stage I, II and III LSCD, respectively (p < 0.001). The CoVT was 51.0 ± 19.4, 113.7 ± 36.6, 129.7 ± 39.3 and 336.0 ± 85.0 µm, respectively (p < 0.001). There was a significant difference in CoVE and CoVT between all stages compared to controls, and between stage I and III LSCD (p < 0.001). Further, CoVE showed a significant difference between stage I and II, whereas CoVT showed a significant difference between stage II and III LSCD (p < 0.001). BCVA showed strong correlation with CoVT (r = 0.765, p < 0.001) and moderate correlation with CoVE (r = 0.547, p = 0.001). AS-OCTA parameters showed excellent intra- and inter-class correlation coefficients (>0.900). CONCLUSION: LSCD demonstrates significant changes in CoVE and CoVT as early as stage I LSCD in comparison to controls. CoVE and CoVT strongly correlate to both disease severity and BCVA. AS-OCTA may provide novel quantitative and non-invasive parameters to assess LSCD.

Novel Parameters to Assess the Severity of Corneal Neovascularization Using Anterior Segment Optical Coherence Tomography Angiography.

PURPOSE: Assessment of anterior segment-optical coherence tomography angiography (AS-OCTA) to determine severity of corneal neovascularization (CoNV). DESIGN: Retrospective, cross-sectional, single-center study. METHODS: Patients of various CoNV etiologies were selected and classified into mild, moderate, and severe. Their AS-OCTA images were measured for CoNV anterior limit, CoNV posterior limit, CoNV thickness, CoNV depth%, CoNV vessel density, CoNV area, and CoNV volume. Further, AS-OCTA parameters were correlated to clinical parameters, such as classification, a numerical severity scale, vascular clock hours, and best-corrected visual acuity (BCVA). RESULTS: A total of 19 mild, 10 moderate, and 6 severe CoNV eyes were included with no significant age-gender differences. CoNV depth% and volume increased from mild to moderate (9.3 ± 1.1% to 17.7 ± 3.3%, P = .030, and 0.2 ± 0.1 mm3 to 1.0 ± 0.3 mm3, P = .025, respectively) and from moderate to severe CoNV (44.6 ± 5.3%, P < .001, and 2.0 ± 0.3 mm3, P = .014, respectively). CoNV area and posterior limit increased from mild to moderate (1.7 ± 0.3 mm2 to 4.6 ± 0.7 mm2, P = .001, and 217.7 ± 16.8 µm to 349.1 ± 54.9 µm, P = .048, respectively), not from moderate to severe (P = .999 and P = .403, respectively). CoNV thickness increased from moderate to severe (218.2 ± 46.6 µm to 340.2 ± 8.7 µm, P = .020), but not from mild to moderate. CoNV area and volume showed good correlations to CoNV staging (r = 0.703 and r = 0.771, respectively; P < .001) and severity scale (r = 0.794 and r = 0.712, respectively; P < .001). CoNV area showed good correlation to clock hours (r = 0.749, P < .001). CoNV depth and volume showed good correlation to BCVA (r = 0.744 and r = 0.722, respectively; P < .001). CoNV anterior limit and vessel density showed no significant correlations (P ≥ .05). CONCLUSIONS: Severe CoNV shows greater CoNV posterior limit, thickness, depth%, area, and volume on AS-OCTA compared to mild. CoNV volume and depth strongly correlate to BCVA. AS-OCTA provides novel, quantitative, and noninvasive parameters for assessing CoNV severity.

A Review of Imaging Biomarkers of the Ocular Surface.

A biomarker is a "characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions." Recently, calls for biomarkers for ocular surface diseases have increased, and advancements in imaging technologies have aided in allowing imaging biomarkers to serve as a potential solution for this need. This review focuses on the state of imaging biomarkers for ocular surface diseases, specifically non-invasive tear break-up time (NIBUT), tear meniscus measurement and corneal epithelial thickness with anterior segment optical coherence tomography (OCT), meibomian gland morphology with infrared meibography and in vivo confocal microscopy (IVCM), ocular redness with grading scales, and cellular corneal immune cells and nerve assessment by IVCM. Extensive literature review was performed for analytical and clinical validation that currently exists for potential imaging biomarkers. Our summary suggests that the reported analytical and clinical validation state for potential imaging biomarkers is broad, with some having good to excellent intra- and intergrader agreement to date. Examples of these include NIBUT for dry eye disease, ocular redness grading scales, and detection of corneal immune cells by IVCM for grading and monitoring inflammation. Further examples are nerve assessment by IVCM for monitoring severity of diabetes mellitus and neurotrophic keratitis, and corneal epithelial thickness assessment with anterior segment OCT for the diagnosis of early keratoconus. However, additional analytical validation for these biomarkers is required before clinical application as a biomarker.

Projection-Resolved Optical Coherence Tomography Angiography Parameters to Determine Severity in Diabetic Retinopathy.

Purpose: The purpose of this study was to assess projection-resolved optical coherence tomography angiography (PR-OCTA) vessel density (VD) and foveal avascular zone (FAZ) in determining severity within diabetic retinopathy (DR) and their accuracy in identifying high-risk DR patients. Methods: This was a retrospective study with 72 eyes of 52 DR patients, assessing the VD and FAZ area of the superficial capillary plexus (SCP) and deep vascular plexus (DVP), for both 3 × 3-mm and 6 × 6-mm scans between the DR groups (mild to moderate, severe and proliferative DR [PDR]). For accuracy, the severe and PDR groups were merged, representing the high-risk DR group for receiver operator characteristic analysis. VD of OCTA images with and without PR were compared. Results: In mild to moderate, severe, and PDR groups, there were 31, 21, and 20 eyes, respectively. PR-OCTA improved VD analysis only in the DVP and particularly in advanced DR stages (P = 0.042). In the 3 × 3-mm PR scans, all superficial and deep parameters were significantly different between severe and PDR groups (P ≤ 0.020), but only the mean VD of SCP and DVP was also significant between the mild to moderate and severe groups (P ≤ 0.007). In the 6 × 6-mm scans, the superficial VD, deep VD, and superficial FAZ were significantly different between the severe and PDR groups (P ≤ 0.029). The superficial VD and deep VD of the 3 × 3-mm scans were good parameters for detecting high-risk patients (area under the curve = 0.829 and 0.895, respectively). Conclusions: PR-OCTA improved VD analysis of DVP. The 3 × 3-mm SCP and DVP VD were the most accurate in detecting high-risk DR.