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Purpose To evaluate the relationship between the occurrence of optic disc hemorrhages (DH) and glaucoma progression as determined by multiple glaucoma testing modalities. Design A prospective cohort study. Methods A longitudinal study of 124 open angle glaucoma patients who had yearly disc photography (DP), visual fields (VFs), spectral-domain optical coherence tomography (SD-OCT) retinal nerve fiber layer (RNFL) thickness scans, and optic nerve volume scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany), all performed on the same day over a 5-year period. The minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter, was calculated from optic nerve volume scans. Patients were classified as glaucoma progressors or non-glaucoma progressors using event-based analysis. Results Out of 124 open angle glaucoma patients, 19 (15.3%) had one or more DHs on yearly DPs. Presence of a DH was associated with localized 3D neuroretinal rim thickness progression (superior MDB progression; OR 3.96, P = 0.04), but not with global or inferior MDB progression (P = 0.14 and 0.81 respectively), DP progression (P = 0.08), VF progression (P = 0.45), or RNFL global, inferior or superior progression (P = 0.17, 0.26 and 0.76 respectively). In the majority of patients with MDB progression (14/17, or 82%), the progression was noted before or concurrently with the first instance of DH. Conclusions Glaucoma progression detected by high-density 3D SD-OCT neuroretinal rim measurements preceded DH occurrence in the majority of patients. These findings support the hypothesis that DHs are indicators of ongoing glaucoma progression rather than discrete events that cause subsequent progression.

Purpose To develop and evaluate the performance of a 3-dimensional (3D) deep-learning–based automated digital gonioscopy system (DGS) in detecting 2 major characteristics in eyes with suspected primary angle-closure glaucoma (PACG): (1) narrow iridocorneal angles (static gonioscopy, Task I) and (2) peripheral anterior synechiae (PAS) (dynamic gonioscopy, Task II) on OCT scans. Design International, cross-sectional, multicenter study. Participants A total of 1.112 million images of 8694 volume scans (2294 patients) from 3 centers were included in this study (Task I, training/internal validation/external testing: 4515, 1101, and 2222 volume scans, respectively; Task II, training/internal validation/external testing: 378, 376, and 102 volume scans, respectively). Methods For Task I, a narrow angle was defined as an eye in which the posterior pigmented trabecular meshwork was not visible in more than 180° without indentation in the primary position captured in the dark room from the scans. For Task II, PAS was defined as the adhesion of the iris to the trabecular meshwork. The diagnostic performance of the 3D DGS was evaluated in both tasks with gonioscopic records as reference. Main Outcome Measures The area under the curve (AUC), sensitivity, and specificity of the 3D DGS were calculated. Results In Task I, 29.4% of patients had a narrow angle. The AUC, sensitivity, and specificity of 3D DGS on the external testing datasets were 0.943 (0.933–0.953), 0.867 (0.838–0.895), and 0.878 (0.859–0.896), respectively. For Task II, 13.8% of patients had PAS. The AUC, sensitivity, and specificity of 3D DGS were 0.902 (0.818–0.985), 0.900 (0.714–1.000), and 0.890 (0.841–0.938), respectively, on the external testing set at quadrant level following normal clinical practice; and 0.885 (0.836–0.933), 0.912 (0.816–1.000), and 0.700 (0.660–0.741), respectively, on the external testing set at clock-hour level. Conclusions The 3D DGS is effective in detecting eyes with suspected PACG. It has the potential to be used widely in the primary eye care community for screening of subjects at high risk of developing PACG.

Purpose: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, 2-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and 3-dimensional (3D) spectral-domain (SD) OCT neuroretinal rim measurements. Design: Prospective, longitudinal cohort study. Participants: One hundred twenty-four eyes of 124 patients with open-angle glaucoma. Methods: Over a 5-year period, 124 patients with open-angle glaucoma underwent yearly DP, VF testing, SD OCT RNFL thickness scans, and optic nerve volume scans (Spectralis; Heidelberg Engineering), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or nonglaucoma progressors using event-based analysis. Progression by DP and VF testing occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if change of more than test–retest variability was observed. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa Coefficients were used to measure agreement of progressing eyes among methods. Main Outcome Measures: Time to glaucoma progression among all 4 methods. Results: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared with DP (16.1%; P < 0.001) and global RNFL thickness (15.3%; P < 0.001). Global MDB thickness detected glaucoma progression earlier than either DP (23 months vs. 44 months; P < 0.001) or global RNFL thickness (23 months vs. 33 months; P < 0.001). Among MDB progressing eyes, 46.2% were confirmed simultaneously or later by other conventional methods. Agreement of glaucoma-progressing eyes for all 4 methods in paired fashion were slight to fair (κ = 0.095–0.300). Conclusions: High-density 3D SD OCT neuroretinal rim measurements detected glaucoma progression approximately 1 to 2 years earlier compared with current clinically available structural tests (i.e., DP and 2D RNFL thickness measurements).

Janice Kim,1– 3 Clara J Men,2,4 Kitiya Ratanawongphaibul,1,2,5 Georgia Papadogeorgou,6 Edem Tsikata,1,2 Geulah S Ben-David,1,2,7 Hussein Antar,1,8 Linda Yi-Chieh Poon,1,9 Madeline Freeman,1,10 Elli A Park,1,11 Maria A Guzman Aparicio,1,2 Johannes F de Boer,12,13 Teresa C Chen1,2 1Department of Ophthalmology, Glaucoma Service, Massachusetts Eye and Ear Infirmary, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA; 4Shiley Eye Institute at University of California, San Diego, CA, USA; 5Center of Excellence in Glaucoma, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; 6Department of Statistics, University of Florida, Gainesville, FL, USA; 7Department of Ophthalmology, Emek Medical Center, Afula, Israel; 8University of Massachusetts Medical School, Worcester, MA, USA; 9Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 10Smith College School for Social Work, Northampton, MA, USA; 11Boston University School of Medicine, Boston, MA, USA; 12LaserLaB Amsterdam, Department of Physics and Astronomy, Vrije Universiteit, Amsterdam, The Netherlands; 13Department of Ophthalmology, Amsterdam University Medical Centers, Amsterdam, The NetherlandsCorrespondence: Teresa C Chen, Department of Ophthalmology, Glaucoma Service, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA, 02114, USA, Tel +1 (617) 573-3674, Fax +1 (617) 573-3707, Email teresa_chen@meei.harvard.eduPurpose: To compare the reproducibility of two-dimensional (2D) peripapillary retinal nerve fiber layer (RNFL) thickness and three-dimensional (3D) neuroretinal rim measurements using spectral domain optical coherence tomography (SDOCT) in normal and glaucoma subjects.Methods: One eye per subject for 27 normal and 40 glaucoma subjects underwent repeat SDOCT RNFL thickness scans and optic nerve volume scans on the same day. From the volume scan, custom software calculated five neuroretinal rim parameters: 3D minimum distance band (MDB) thickness, 3D MDB area, 3D rim volume, 2D rim area, and 2D rim thickness. Within-subject variance (Sw), coefficient of variation (CV), and intraclass correlation coefficient (ICC) were analyzed.Results: MDB thickness and RNFL thickness have similar reproducibility among normal and glaucoma subjects (eg, global MDB thickness CVs of 2.4% and 3.6%, and global RNFL thickness CVs of 1.3% and 2.2%; P > 0.05 for both comparisons). Reproducibility of MDB thickness was lower in glaucoma patients for the superior and inferior quadrants compared to normal subjects (CVs of 9.6% versus 3.4% and 6.9% versus 2.7%; P < 0.05, respectively). There were no statistically significant differences between both groups for RNFL thickness in the four quadrants. For both patient groups and for all regions, MDB thickness had the lowest CVs among all five neuroretinal rim parameters (eg, global MDB thickness CVs of 2.4% and 3.6% versus 3.0% and 18.9% for the other four neuroretinal rim parameters).Conclusion: Global MDB and global RNFL thickness are similarly reproducible among normal and glaucoma subjects, though MDB thickness for the superior and inferior quadrants is less reproducible among glaucoma subjects.Keywords: glaucoma, optical coherence tomography, reproducibility, optic nerve, minimum distance band

Précis: Neuroretinal rim minimum distance band (MDB) thickness is significantly lower in older subjects and African Americans compared with whites. It is similar in both sexes. Purpose: To evaluate the relationship between age, race, and sex with the neuroretinal rim using high-density spectral-domain optical coherence tomography optic nerve volume scans of normal eyes. Methods: A total of 256 normal subjects underwent Spectralis spectral-domain optical coherence tomography optic nerve head volume scans. One eye was randomly selected and analyzed for each subject. Using custom-designed software, the neuroretinal rim MDB thickness was calculated from volume scans, and global and quadrant neuroretinal rim thickness values were determined. The MDB is a 3-dimensional neuroretinal rim band comprised of the shortest distance between the internal limiting membrane and the termination of the retinal pigment epithelium/Bruch’s membrane complex. Multiple linear regression analysis was performed to determine the associations of age, race, and sex with neuroretinal rim MDB measurements. Results: The population was 57% female and 69% white with a mean age of 58.4±15.3 years. The mean MDB thickness in the normal population was 278.4±47.5 µm. For this normal population, MDB thickness decreased by 0.84 µm annually (P

To determine the efficacy of azithromycin 1.5% eyedrops compared with oral doxycycline in patients with moderate to severe meibomian gland dysfunction (MGD). This prospective randomized trial included 169 participants with newly diagnosed moderate to severe MGD. Participants were randomly assigned to treatment with azithromycin 1.5% eyedrops (n = 85) twice daily for 2 days then once daily until 4 weeks or oral doxycycline (n = 84) 100 mg twice daily for 4 weeks. Signs and symptoms of MGD were evaluated at baseline and 4 weeks later. The percentages of participants with improvement in meibum quality were assessed as a primary outcome. Secondary outcomes were MGD-related symptoms, meibum expressibility, Oxford ocular surface staining score, tear film break up time (TBUT), and drug side effects. Although there were significant improvements in all outcomes in both groups, there was no between-group differences in the percentages of participants with improved meibum quality (P = 0.80), MGD-related symptoms (P > 0.05), meibum expressibility (P = 0.92), Oxford ocular surface staining score (P = 0.59), and TBUT (P = 0.99). Five (5.88%) participants in azithromycin group and four (4.76%) participants in doxycycline group discontinued medications due to drug side effects (P = 0.75). Both azithromycin 1.5% eyedrops and oral doxycycline significantly improved signs and symptoms in patients with moderate to severe MGD. Both azithromycin 1.5% eyedrops and oral doxycycline showed no difference in term of improved signs and symptoms of MGD as well as drug side effects that lead to discontinuation of medication.

Ocular pythiosis is the second most common form of human pythiosis, and the rates of evisceration/enucleation in Thailand are 55–79%. This prospective study was conducted to evaluate treatment outcomes of the combination therapy protocol and the potential use of serum (1→3)-β-glucan (BG) and Pythium insidiosum-specific antibody (Pi-Ab) as an aid to diagnosis and monitoring of ocular pythiosis. Thirty patients were enrolled in the study and 14 (non-globe salvage) required evisceration/enucleation. The globe salvage group was significantly younger, and first ocular surgeries were performed significantly sooner than in the non-globe salvage group. Serum BG and Pi-Ab levels were similar among the 2 groups over time. In vitro susceptibility testing of antifungal agents revealed relatively high minimum inhibitory concentrations and lack of synergistic effect. Serum BG and Pi-Ab would not be useful in diagnosis and monitoring of ocular pythiosis. Until effective antimicrobial agents are discovered, ocular surgeries are still the mainstay therapy in Thailand.

To develop and evaluate the performance of a 3-dimensional (3D) deep-learning-based automated digital gonioscopy system (DGS) in detecting 2 major characteristics in eyes with suspected primary angle-closure glaucoma (PACG): (1) narrow iridocorneal angles (static gonioscopy, Task I) and (2) peripheral anterior synechiae (PAS) (dynamic gonioscopy, Task II) on OCT scans.International, cross-sectional, multicenter study.A total of 1.112 million images of 8694 volume scans (2294 patients) from 3 centers were included in this study (Task I, training/internal validation/external testing: 4515, 1101, and 2222 volume scans, respectively; Task II, training/internal validation/external testing: 378, 376, and 102 volume scans, respectively).For Task I, a narrow angle was defined as an eye in which the posterior pigmented trabecular meshwork was not visible in more than 180° without indentation in the primary position captured in the dark room from the scans. For Task II, PAS was defined as the adhesion of the iris to the trabecular meshwork. The diagnostic performance of the 3D DGS was evaluated in both tasks with gonioscopic records as reference.The area under the curve (AUC), sensitivity, and specificity of the 3D DGS were calculated.In Task I, 29.4% of patients had a narrow angle. The AUC, sensitivity, and specificity of 3D DGS on the external testing datasets were 0.943 (0.933-0.953), 0.867 (0.838-0.895), and 0.878 (0.859-0.896), respectively. For Task II, 13.8% of patients had PAS. The AUC, sensitivity, and specificity of 3D DGS were 0.902 (0.818-0.985), 0.900 (0.714-1.000), and 0.890 (0.841-0.938), respectively, on the external testing set at quadrant level following normal clinical practice; and 0.885 (0.836-0.933), 0.912 (0.816-1.000), and 0.700 (0.660-0.741), respectively, on the external testing set at clock-hour level.The 3D DGS is effective in detecting eyes with suspected PACG. It has the potential to be used widely in the primary eye care community for screening of subjects at high risk of developing PACG.

Purpose: To describe a case of microsporidial stromal keratitis with endophthalmitis in an immunocompetent patient.Methods: Case reportResults: A 58-year-old HIV-negative man presented with stromal keratitis in his right eye. The patient demonstrated subsequent vitritis, multifocal retinitis and arteritis, and macular edema with recurrent vitreous hemorrhage after therapeutic keratoplasty. Numerous microsporidial spores were detected in corneal tissues by modified trichrome stain. Both corneal tissues and vitreous sample of the affected eye showed positive results by polymerase chain reaction targeting the microsporidial small subunit rRNA gene whose sequences belonged to Vittaforma corneae. Post-keratoplasty and vitrectomy, his best-corrected visual acuity was hand motion due to pale optic disc.Conclusion: Endophthalmitis can be a consequence of microsporidial stromal keratitis in an immunocompetent host. Early recognition and prompt treatment should be considered in patients diagnosed with microsporidial keratitis presenting with mild vitritis, retinitis, and recurrent vitreous hemorrhage.

Background/aimsTo assess the effect of partial posterior vitreous detachment (pPVD) on spectral-domain optical coherence tomography (OCT) peripapillary retinal nerve fibre layer thickness (RNFL) measurements.MethodsSpectral-domain OCT RNFL thickness measurements were obtained from 684 consecutive patients who were seen in the Massachusetts Eye and Ear Glaucoma Service. Of these patients, we compared RNFL thickness measurements between 101 eyes of 101 glaucoma suspects who met inclusion criteria (55 eyes with and 46 eyes without pPVD).ResultsAmong all 684 patients, 253 (37%) had pPVD in at least one eye. Among a subset of 101 eyes of 101 glaucoma suspects, average RNFL thickness was greater in eyes with compared to eyes without pPVD (p=0.02). Measurements were significantly greater in the inferior (p=0.004) and superior quadrants (p=0.008), but not in the nasal (p=0.10) and temporal quadrants (p=0.25). The difference in average RNFL thickness remained significant (p=0.05) even when corrected for expected age-related decline in RNFL thickness.ConclusionOver a third of patients were found on peripapillary spectral-domain OCT to have a pPVD, which was associated with greater RNFL thickness measurements. Judicious clinical interpretation of this finding on spectral-domain OCT RNFL thickness scans should be factored into the assessment of glaucoma suspects.

Background Vascular pythiosis, caused by Pythium insidiosum, is a life-threatening disease despite aggressive treatment. Our recent study showed that serum β-d-glucan (BG) trends can be used to monitor disease activity after treatment initiation. A significant decline in BG by 0.5 month indicated complete resection without residual disease. However, BG assay is cost probihitive and available only at King Chulalongkorn Memorial Hospital in Thailand. This study was conducted to preliminarily evaluate erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as monitoring tools. Methods A prospective study included proven vascular pythiosis patients receiving treatment with combination therapy from November 2018 to January 2019. Clinical information, BG, ESR, and CRP were collected at 0, 0.5, 1.5, and 3 months post diagnosis. Spearman’s correlation coefficient and analysis of response profiles were used. Results Six patients were enrolled. All had thalassemia. Four developed disease at popliteal artery, 1 at common iliac artery, and 1 at brachial artery. All underwent amputation with negative surgical margins achievement. All received itraconazole, azithromycin, and P. insidiosum immunotherapy. One received terbinafine and one received doxycycline additionally. All had positive BG > 500 pg/mL at diagnosis. After treatment initiation, means of ESR were significantly decreased at 0.5 months (P = 0.02). Means of CRP were not significantly changed until 1 month (P = 0.02) (Figure 1a and b). Correlation coefficients between BG and ESR vs. BG and CRP were 0.74 and 0.65, respectively. All survived without relapse at 3 months. Conclusion ESR and CRP are potentially valuable markers to monitor vascular pythiosis in resource-limited countries. However, ESR levels and trends seem to be correlated with BG better than CRP. Further studies are needed to enroll more patients, especially patients with incomplete resection or non-surgical candidates. Disclosures All authors: No reported disclosures.

Background β-d-glucan (BG) detection was first available in Thailand in 2016 to aid diagnosis of invasive fungal infections (IFIs). Given a paucity of real-world experience of BG use in resource-limited countries, this study was conducted to describe appropriateness of BG testing and sequelae of BG results. Methods A retrospective study included all patients with at least 1 BG ordered at King Chulalongkorn Memorial Hospital, Bangkok, Thailand during March 2016 to December 2018. Descriptive statistics were used. Results 83 patients were tested by BG assay (Fungitell, Associates of Cape Cod, Inc.): 6 with hematopoietic stem cell transplant, 12 with solid-organ transplant, 20 with active cancer receiving chemotherapy, 34 receiving high dose steroids (≥20 mg/day of prednisone for ≥3 weeks) and 11 with other conditions. Seventy-three patients were tested under infectious disease (ID) service’s recommendations. There were 13 and 20 cases of proven and probable IFIs, respectively. Among 13 proven IFIs, there were 11 positive, 1 indeterminate and 1 negative (mucormycosis) BG results. Among 49 cases with positive BG results, 24 were determined to be false-positive results. Median turn-around time for BG results was 16 (IQR: 9–23) days. Due to high turn-around time, only 8 patients were started on antifungal agent(s) and 3 underwent bronchoscopy due to positive BG results. All proven IFI cases were started on antifungal treatment prior to BG availability. Conclusion Approximately 87% of BG use in Thailand was ordered in patients with risk factors for IFIs. This could be due to majority of BG test was recommended by ID specialist. Despite being used in right clinical context, 49% had false-positive BG results. Another barrier of BG use in Thailand was high turn-around time due to small numbers of BG ordered and relative high cost to run the assay. Therefore, the utility of BG for aiding diagnosis or management of fungal infection in our setting is limited. Disclosures All authors: No reported disclosures.